WO2007066496A1 - Benzoylurea compound and use thereof - Google Patents

Benzoylurea compound and use thereof Download PDF

Info

Publication number
WO2007066496A1
WO2007066496A1 PCT/JP2006/323048 JP2006323048W WO2007066496A1 WO 2007066496 A1 WO2007066496 A1 WO 2007066496A1 JP 2006323048 W JP2006323048 W JP 2006323048W WO 2007066496 A1 WO2007066496 A1 WO 2007066496A1
Authority
WO
WIPO (PCT)
Prior art keywords
optionally substituted
group optionally
substituents
halogen atoms
group
Prior art date
Application number
PCT/JP2006/323048
Other languages
French (fr)
Inventor
Masato Konobe
Shigeyuki Itoh
Norihisa Sakamoto
Tomohiro Araki
Original Assignee
Sumitomo Chemical Company, 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
Application filed by Sumitomo Chemical Company, Limited filed Critical Sumitomo Chemical Company, Limited
Publication of WO2007066496A1 publication Critical patent/WO2007066496A1/en

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
    • C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
    • C07D295/12—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms
    • C07D295/125—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms with the ring nitrogen atoms and the substituent nitrogen atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
    • C07D295/13—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms with the ring nitrogen atoms and the substituent nitrogen atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N47/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid
    • A01N47/08—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid the carbon atom having one or more single bonds to nitrogen atoms
    • A01N47/28—Ureas or thioureas containing the groups >N—CO—N< or >N—CS—N<
    • A01N47/34—Ureas or thioureas containing the groups >N—CO—N< or >N—CS—N< containing the groups, e.g. biuret; Thio analogues thereof; Urea-aldehyde condensation products
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C275/00—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups
    • C07C275/46—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups containing any of the groups, X being a hetero atom, Y being any atom, e.g. acylureas
    • C07C275/48—Y being a hydrogen or a carbon atom
    • C07C275/54—Y being a carbon atom of a six-membered aromatic ring, e.g. benzoylureas
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/72—Nitrogen atoms
    • C07D213/75—Amino or imino radicals, acylated by carboxylic or carbonic acids, or by sulfur or nitrogen analogues thereof, e.g. carbamates
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D213/81—Amides; Imides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D309/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings
    • C07D309/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
    • C07D309/08—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D309/10—Oxygen atoms
    • C07D309/12—Oxygen atoms only hydrogen atoms and one oxygen atom directly attached to ring carbon atoms, e.g. tetrahydropyranyl ethers

Definitions

  • the present invention relates to a benzoylurea
  • JP 61-15879 A and the like disclose benzoylurea compounds having a pest controlling activity.
  • An object of the present invention is to provide a compound having an excellent controlling efficacy for pests.
  • the present invention relates to the
  • X and Y each represent independently an oxygen atom or a sulfur atom
  • R 1 represents a hydrogen atom
  • R 2 represents a lower alkylene group optionally substituted with one or more halogen atoms
  • A represents:
  • R 3 represents a C1-C3 alkyl group optionally substituted with one or more substituents
  • R 4 represents a C1-C3 alkyl group optionally substituted with one or more substituents
  • n an integer of 0, 1 or 2)
  • R 5 and R 6 may be taken together at the ends thereof to form together with the nitrogen atom a 3- to 7-membered nitrogen-containing heterocyclic ring optionally having another nitrogen atom, an oxygen atom or a sulfur atom as a ring constituting atom) ,
  • R 7 represents a halogen atom
  • cyano group an aryl lower alkoxy group optionally substituted with one or more halogen atoms,
  • thiocarbamoyl group optionally substituted with one or more lower alkyl groups
  • G represents an oxygen atom, a 1 sulfur atom, SO, or
  • E represents an aryl group or a heterocyclic group and said aryl group or said heterocyclic group may be
  • a halogen atom substituted with one or more substituents selected from the group consisting of (1) a halogen atom, (2) a lower alkyl group optionally substituted with one or more halogen atoms, (3) a lower alkoxy group optionally substituted with one or more halogen atoms, (4) a lower alkylthio group optionally substituted with one or more halogen atoms, (5) a lower alkylsulfinyl group optionally substituted with one or more halogen atoms, (6) a lower alkylsulfonyl group optionally substituted with one or more halogen atoms, (7) a cyano group, and (8) a nitro group),
  • Q represents an aryl group optionally substituted with one or more substituents, or a heterocyclic group
  • n represents an integer of 1 to 5 (provided that when m is an integer of 2 to 5, R 7 ' s may be the same or
  • G is an oxygen atom, a sulfur atom, SO, or SO 2 .
  • E is an aryl group or a heterocyclic group and said aryl group or said heterocyclic group may be substituted with x ,one or more substituents, selected from the group consisting of (1) a halogen atom, (2) a lower alkyl group optionally substituted with one or more halogen atoms, (3) a lower alkoxy group optionally substituted with one or more halogen atoms, (4) a lower alkylthio group optionally substituted with one or more halogen atoms, (5) a lower alkylsulfinyl group optionally substituted with one or more halogen atoms, (6) a lower alkylsulfonyl group optionally substituted with one or more halogen atoms, (7) a cyano group, and (8) a nitro group) .
  • substituents selected from the group consisting of (1) a halogen atom, (2) a lower alkyl group optionally substituted with one or more halogen atoms,
  • R 2 is a C1-C4 alkylene group optionally substituted with one or more halogen atoms.
  • R 3 is a C1-C3 alkyl group optionally substituted with one or more substituents
  • R 3 is a C1-C3 alkyl group optionally substituted with one or more substituents
  • A is a group represented by S(O) n R 4
  • R 4 is a C1-C3 alkyl group optionally substituted with one or more substituents
  • ri is an integer of 0 to 2) .
  • A is a group represented by NR 5 R 6
  • R 5 and R 6 are taken together at the end thereof to form together with the nitrogen atom a 3- to 7-membered
  • nitrogen-containing heterocycle optionally having another nitrogen atom, an oxygen atom or a sulfur atom as a ring constituting atom
  • an aromatic monocyclic heterocyclic group optionally- substituted with one or more substituents selected from the group consisting of (1) a halogen atom, (2) a lower alkyl group optionally substituted with one or more halogen atoms, and (3) a lower alkoxy group optionally substituted with one or more halogen atoms.
  • R 1 is a hydrogen atom
  • R 2 is a methylene group, an ethylene group, or a trimethylene group
  • A is:
  • R 3 is a C1-C3 alkyl group optionally substituted with one or more substituents
  • R 4 is a C1-C3 alkyl group optionally substituted with one or more substituents
  • n is an integer of 0 to 2)
  • R 5 and R 6 each are independently a C1-C3 alkyl group optionally substituted with one or more substituents, or
  • R 5 and R 6 are taken together at the end thereof to form together with the nitrogen atom a 3- to 7-membered nitrogen-containing heterocycle optionally having another nitrogen atom, an oxygen atom or a sulfur atom as a ring constituting atom) ,
  • R 7 is a halogen atom
  • G is an oxygen atom, or a sulfur atom
  • E is an aryl group or a heterocyclic group optionally substituted with one or more substituents selected from the group consisting of (1) a halogen atom, and (2) a lower alkyl group optionally substituted with one or more halogen atoms) ,
  • Q is a 2, ⁇ -difluorophenyl group, a 2-chloro-6- fluorophenyl group, a 2 , 6-dichlorophenyl group, a 3- chloropyridin-2-yl group, or a 3, 5-dichloropyridin-4-yl group, and
  • n is an integer of 1 to 4 (provided that when m is an integer of 2 to 4, R 7 ' s may be the same or different) .
  • R 1 is a hydrogen atom
  • R 2 is a methylene group, an ethylene group, or a trimethylene group
  • A is:
  • R 3 is a C1-C3 alkyl group optionally substituted with one or more substituents
  • R 4 is a C1-C3 alkyl group optionally substituted with one or more substituents
  • n is an integer of 0 to 2) , or
  • R 5 and R 6 each are independently a C1-C3 alkyl group optionally substituted with one or more substituents, or
  • R 5 and R 6 are taken together at the end thereof to form together with the nitrogen atom a 3- to 7-membered nitrogen-containing heterocycle optionally having another nitrogen atom, an oxygen atom or a sulfur atom as a ring constituting atom) ,
  • R 7 is a halogen atom
  • G is an oxygen atom, or a sulfur atom
  • E is an aryl group or a heterocyclic group and said aryl group or said heterocyclic group may be substituted with one or more substituents selected from the group consisting of (1) a halogen atom, and (2) a lower alkyl group optionally substituted with one or more halogen atoms) ,
  • Q is a 2, 6-difluorophenyl group, a 2-chloro-6- fluorophenyl group, a 2 , 6-dichloro ⁇ henyl group, a 3- chloropyridin-2-yl group, or a 3, 5-dichloropyridin-4-yl group, and
  • n is an integer of 1 to 4 (provided that when m is an integer of 2 to 4, R 7 S may be the same or different) .
  • a pest controlling agent comprising the benzoylurea compound as defined in any one of [1] to [12] or a salt thereof as an active ingredient.
  • a method of controlling pests or plant-parasiting pests which comprises applying an effective amount of the benzoylurea compound as defined in any one of [1] to [12] or a salt thereof to pests or habitats of pests.
  • lower means a group having 6 or less carbon atoms, preferably a group having 4 or less carbon atoms.
  • examples of "one or more” include 1 to 6, more preferably 1 to 4.
  • lower alkyl group and the “lower alkyl” include straight or branched C1-C6 alkyl groups such as methyl, ethyl, n-propyl, 'isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, sec-pentyl, isopentyl, neopentyl, n-hexyl, isohexyl and the like.
  • C1-C3 alkyl group and the "C1-C3 alkyl” - include straight or branched C1-C3 alkyl groups, specifically, methyl, ethyl, n-propyl, and
  • lower alkenyl group examples include straight or branched C2-C6 alkenyl groups such as vinyl, allyl, isopropenyl, isobutenyl, 1-methylallyl, 2- pentenyl, and 2-hexenyl and the like.
  • lower alkynyl group examples include C2-C6 alkynyl groups such as ethynyl, 2-propynyl, 1-propynyl, 2-butynyl, 3-butynyl, 3-pentynyl, 3-hexynyl and the like.
  • aryl group and “aryl” include C6-C14 aromatic hydrocarbon groups such as a phenyl group optionally substituted with lower alkyl (e.g. phenyl, mesityl, xylyl, tolyl etc.), naphthyl, anthracenyl and the like, preferably phenyl and naphthyl, and this "aryl group” and “aryl” may have a suitable substituent such as lower alkyl group, halogen, aryl group and the like.
  • halogen and the "halogen atom” include fluorine, chlorine, bromine and iodine.
  • the "lower alkoxy group” and the “lower alkoxy” include straight or branched C1-C6 alkoxy groups such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, tert-butoxy, pentyloxy, tert-pentyloxy, neopentyloxy, hexyloxy, isohexyloxy and the like, more preferably methoxy, ethoxy, propoxy, butoxy, pentyloxy, hexyloxy, and isohexyloxy.
  • lower alkanoyl group examples include straight or branched C1-C6 alkanoyl groups such as acetyl, 2-methylacetyl, 2, 2-dimethylacetyl, propionyl, butyryl, isobutyryl, pentanoyl, 2 , 2-dimethylpropionyl, hexanoyl and the like.
  • lower cycloalkyl group examples include cyclic C3-C6 alkyl groups such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and the like.
  • heterocyclic group examples include 5- to 14- membered, preferably 5- to 10-membered monocyclic to tricyclic, preferably monocyclic or dicyclic heterocyclic groups containing one or two kinds of 1 to 4, preferably 1 to 3 hetero atoms selected from a nitrogen atom, an oxygen atom and a sulfur atom in addition to carbon atoms as a ring constituting atom, specifically,
  • 5-membered heterocyclic groups such as 2-thienyl, 3- thienyl, 2-furyl, 3-furyl, 2-pyrrolyl, 3-pyrrolyl, 2- pyrrolidinyl, 3-pyrrolidinyl, 2-oxazolyl, 4-oxazolyl, 5- oxazolyl, 3-isoxazolyl, 4-isoxazolyl, 5-isoxazolyl, 2- thiazolyl, 4-thiazolyl, 5-thiazolyl, 3-isothiazolyl, 4- isothiazolyl, 5-isothiazolyl, 3-pyrazolyl, 4-pyrazolyl, 5- pyrazolyl, 2-pyrazolidinyl, 3-pyrazolidinyl, 4- pyrazolidinyl, 2-imidazolyl, 4-imidazolyl, 5-imidazolyl, lH-l,2,3-triazol-4-yl, IH-I, 2, 3-triazol-5-yl, 1,2,4- tria
  • 6-membered heterocyclic groups such as 2-pyridyl, 3- pyridyl, 4-pyridyl, N-oxide-2-pyridyl, N-oxide-3-pyridyl, N-oxide-4-pyridyl, 2-pyrimidinyl, 4-pyrimidinyl, 5- pyrifnidinyl, N-oxide-2-pyrimidinyl, N-oxide-4-pyrimidinyl, N-oxide-5-pyrimidinyl, 2-thiomorpholinyl, 3-thiomorpholinyl, 2-morpholinyl, 3-morpholinyl, 2-piperidyl, 3-piperidyl, 4- piperidyl, 2-thiopyranyl, 3-thiopyranyl, 4-thiopyranyl, 2- 4H-1, 4-oxazinyl, 3-4H-1, 4-oxazinyl, 2-4H-1, 4-thiazinyl, 3- 4H-1, 4-thiazinyl, 2-piperazinyl, 3-1
  • dicyclic or tricyclic fused heterocyclic groups such as 1-indolyl, 3-indolyl, 4-indolyl, 5-indolyl, 6-indolyl, 7-indolyl, 2-benzofuryl, 3-benzofuryl, 4-benzofuryl, 5- benzofuryl, ⁇ -benzofuryl, 7-benzofuryl, 2-benzothiazolyl, 4-benzothiazolyl, 5-benzothiazolyl, ⁇ -benzothiazolyl, 7- benzothiazolyl, 2-benzoxazolyl, 4-benzoxazolyl, 5- benzoxazolyl, 6-benzoxazolyl, 7-benzoxazolyl, 2- benzimidazolyl, 4-benzimidazolyl, 5-benzimidazolyl, 6- benzimidazolyl, 7-benzimidazolyl, 2-quinolyl, 3-quinolyl, 4-quinolyl, 5-quinolyl, 6-quinolyl, 7-quinoly
  • heterocyclic group inter alia, a 5-, 6- or 7-membered (preferably 5- or 6-membered) heterocyclic group containing 1 to 3 hetero atoms selected from the group consisting of an oxygen atom, a sulfur atom and a nitrogen atom ⁇ in addition to carbon atoms is preferable.
  • heterocyclic group examples include 5- or 6-membered heterocyclic groups containing 1 to 3 hetero atoms selected from the group consisting of a nitrogen atom, an oxygen atom and a sulfur atom in addition to carbon atoms, specifically, such as 1-pyrrolidinyl, 2- pyrrolidinyl, 3-pyrrolidinyl, 2-imidazolinyl, 4- imidazolinyl, 2-pyrazolizinyl, 3-pyrazolizinyl, A- pyrazolizinyl, 1-piperidyl, 2-piperidyl, 3-piperidyl, A- piperidyl, 2-piperidyl, 3-piperidyl, 4-piperidyl, 1- piperazinyl, 2-piperazinyl, morpholinyl, 2-thienyl, 3- thienyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-furyl, 3-furyl, pyrazinyl, 2-pyrimi
  • heterocyclic group examples include an "aromatic heterocyclic group", for example, 5- to 14-membered, more preferably 5- to 10-membered
  • monocyclic to tricyclic further more preferably monocyclic or dicyclic aromatic heterocyclic groups containing one kind or two kinds or 1 to 4, preferably 1 to 3 hetero atoms selected from a nitrogen atom, an oxygen atom and a sulfur atom in addition to carbon atoms as a ring constituting atom, specifically, 5-membered aromatic heterocyclic groups such- as 2-thienyl, 3-thienyl, 2-furyl, 3-furyl, 1-pyrrolyl, 2-pyrrolyl, 3-pyrrolyl, 2-oxazolyl, 4-oxazolyl, 5-oxazolyl, 3-isoxazolyl, 4-isoxazolyl, 5-isoxazolyl, 2-thiazolyl, 4- thiazolyl, 5-thiazolyl, 3-isothiazolyl, 4-isothiazolyl, 5- isothiazolyl, 3-pyrazolyl, • 4-pyrazolyl, 5-pyrazolyl, 2- imidazolyl, 4-imidazolyl, 5-
  • 6-membered aromatic heterocyclic groups such as 2- pyridyl, 3-pyridyl, 4-pyridyl, N-oxide-2-pyridyl, N-oxide- 3-pyridyl, N-oxide-4-pyridyl, 2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl, N-oxide-2-pyrimidinyl, N-oxide-4-pyrimidinyl, N-oxide-5-pyrimidinyl, 3-1, 2 , 4-triazinyl, 5-1, 2 , 4-triazinyl, 6-1,2, 4-triazinyl, 2-1, 3, 5-triazinyl, 3-pyridazinyl, A- pyridazinyl, 2-pyrazinyl, N-oxide-3-pyridazinyl, N-oxide-4- pyridazinyl and the like, and
  • aromatic heterocyclic group examples include 5- or 6-membered heterocyclic groups
  • hetero atoms selected from the group consisting of a nitrogen atom, an oxygen atom, and a sulfur atom in addition to carbon atoms, specifically, such as 2- thienyl, 3-thienyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2- furyl, 3-furyl, pyrazinyl, 2-pyrimidinyl, 3-pyrrolyl, 3- pyridazinyl, 3-isothiazolyl, and 3-isoxazolyl, particularly preferably, 6-membered nitrogen-containing aromatic
  • heterocyclic groups e.g. pyridyl etc.
  • heterocyclic groups e.g. pyridyl etc.
  • heterocyclic group examples include an "aromatic monocyclic heterocyclic group", for example, 5-membered aromatic monocyclic heterocyclic groups such as 2-furyl, 3-furyl, 2-thienyl, 3-thienyl, 2- pyrrolyl, 3-pyrrolyl, 2-oxazolyl, 4-oxazolyl, 5-oxazolyl, 3-isoxazolyl, 4-isoxazolyl, 5-isoxazolyl, 2-thiazolyl, 4- thiazolyl, 5-thiazolyl, 3-isothiazolyl, '4-isothiazolyl, 5- isothiazolyl, 2-imidazolyl, 4-imidazolyl, 5-imidazolyl, 3- pyrazolyl, 4-pyrazolyl, 5-pyrazolyl, 1, 2 , 3-oxadiazol-4-yl, 1, 2, 3-oxadiazol-5-yl, 1, 2, 4-oxadiazol-5-yl, 1,2,4- o
  • ⁇ -membered aromatic monocyclic heterocyclic groups such N as 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyrimidinyl, A- pyrimidinyl, 5-pyrimidinyl, 3-pyridazinyl, 4-pyridazinyl, 2-pyrazinyl, 1, 2, 4-triazin-3-yl, 1, 2, 4-triazin-5-yl, 1,2,4- triazin- ⁇ -yl, 1, 3, 5-triazin-2-yl and the like.
  • lower alkylsulfonyl group in the “lower alkylsulfonyl group optionally substituted with one or more substituents” represented by R 1 include methylsulfonyl, ethylsulfonyl, n-propylsulfonyl,
  • substituents of the "one or more substituents" in the "lower alkylsulfonyl group optionally substituted with one or more substituents” include a halogen atom (fluorine atom, chlorine atom, bromine atom, iodine atom), nitro, cyano, hydroxyl, lower cycloalkyl optionally substituted with a halogen atom (e.g. cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl etc.), lower alkoxy (e.g.
  • amino, mono- or di- (lower alkyl) amino e.g. methylamino, ethylamino, dimethylamino, diethylamino etc.
  • carboxyl e.g. acetyl, propionyl etc.
  • lower alkoxycarbonyl e.g. methoxycarbonyl, ethoxycarbonyl, propoxycarbony
  • carbamoyl e.g. methylcarbamoyl,
  • arylcarbamoyl e.g. phenylcarbamoyl, naphthylcarbamoyl etc.
  • aryloxy e.g. phenyloxy, naphthyloxy etc.
  • lower alkylcarbonylamino optionally substituted with a halogen atom (e.g. acetylamino, trifluoroacetylamino etc.), lower alkylthio (e.g. methylthio etc.), lower alkylsulfinyl (e.g. methylsulfinyl etc.), lower alkylsulfonyl (e.g.
  • arylsulfinyl e.g. phenylsulfinyl, naphthylsulfinyl etc.
  • arylsulfonyl e.g. phenylsulfonyl, naphthylsulfonyl etc.
  • halogen atom fluorine atom, chlorine atom, bromine atom, iodine atom
  • halogen atom e.g. chloromethyl
  • cycloalkyl optionally substituted with a halogen atom (e.g. cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl etc.), lower alkoxy (e.g. methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, pentyloxy, hexyloxy etc.), amino, mono- or di- (lower alkyl) amino (e.g. methylamino, ethylamino, dimethylamino, diethylamino etc.), carboxyl, lower alkanoyl (e.g. acetyl, propionyl etc.), lower alkoxycarbonyl (e.g. methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl,
  • a halogen atom e.g. cyclopropyl, cyclobutyl, cyclopentyl, cyclohexy
  • carbamoyl, thiocarbamoyl, mono- or di- (lower alkyl) carbamoyl e.g. methylcarbamoyl, ethylcarbamyl, dimethylcarbamoyl, diethylcarbamoyl etc.
  • arylcarbamoyl e.g. phenylcarbamoyl, naphthylcarbamoyl etc.
  • aryloxy e.g. phenyloxy, naphthyloxy etc.
  • lower alkylcarbonylamino optionally substituted with a halogen atom e.g.
  • acetylamino, trifluoroacetylamino etc. lower alkylthio (e.g. methylthio etc.), lower alkylsulfinyl (e.g. methylsulfinyl etc.), lower alkylsulfonyl (e.g.
  • arylsulfinyl e.g. phenylsulfinyl, naphthylsulfinyl etc.
  • arylsulfonyl e.g. phenylsulfonyl, naphthylsulfonyl etc.
  • lower alkoxycarbonylthio group in the “lower alkoxycarbonylthio group optionally substituted with one or more substituents” represented by R 1 include methoxycarbonylthio, ethoxycarbonylthio,
  • butoxycarbonylthio isobutoxycarbonylthio, tert- butoxycarbonylthio, pentyloxycarbonylthio, tert- pentyloxycarbonylthio, neo-pentyloxycarbonylthio,
  • alkyl) aminosulfonyl group optionally sub'stituted with one or more substituents" represented by R 1 include
  • alkyl) aminosulfonyl group optionally substituted with one or more substituents include the same substituent as the "substituent” exemplified for the "lower alklysulfonyl group optionally substituted with one or more substituents".
  • R 1 di (aryl) aminosulfonyl group optionally substituted with one or more substituents" represented by R 1 include
  • Preferable examples of the "lower alkyl group" in the “lower alkyl group optionally substituted with one or more substituents” represented by R 1 include methyl, ethyl, n- propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, sec-pentyl, isopentyl, neopentyl, n-hexyl,
  • halogen atom fluorine atom, chlorine atom, bromine atom, iodine atom
  • nitro, cyano lower alkanoyl (e.g. acetyl, propionyl etc.), lower alkoxycarbonyl (e.g. methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, butoxycarbonyl etc.), lower cycloalkyl optionally substituted with a halogen atom (e.g. cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl etc.), a heterocyclic group, and the like, and
  • heterocyclic group examples include an "aromatic monocyclic heterocyclic group", and examples of the aromatic monocyclic heterocyclic group include 5-membered aromatic monocyclic heterocyclic groups such as 2-furyl, 3-furyl, 2-thienyl, 3-thienyl, 3-pyrrolyl, 3-pyrrolyl, 2-oxazolyl, 4-oxazolyl, 5-oxazolyl, 3- lsoxazolyl, 4-isoxazolyl, 5-isoxazolyl, 2-thiazolyl, 4- thiazolyl, 5-thiazolyl, 3-isothiazolyl, 4-isothiazolyl, 5- lsothiazolyl, 2-imidazolyl, 4-imidazolyl, 5-imidazolyl, 3- pyrazolyl, 4-pyrazolyl, 5-pyrazolyl, 1, 2, 3-oxadiazol-4-yl, 1,2, 3-oxadiazol-5-yl, 1, 2, 4-oxadiazol-5
  • 6-membered aromatic monocyclic heterocyclic groups such as 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyrimidinyl, 4- pyrimidinyl, 5-pyrimidinyl, 3-pyridazinyl, 4-pyridazinyl, 2-pyrazinyl, 1, 2, 4-triazin-3-yl, 1, 2, 4-triazin-5-yl, 1,2,4- triazin- ⁇ -yl, 1, 3, 5-triazin-2-yl and the like.
  • lower alkenyl group in the "lower alkenyl optionally substituted with one or more substituents” represented by R 1 include vinyl, allyl, isopropentyl, isobutenyl, 1-methylallyl, 2-pentenyl, 2- hexenyl and the like, and
  • the "substituent" of the "one or more substitutents" in the "lower alkenyl optionally substituted with one or more substituents” include a halogen atom (fluorine atom, chlorine atom, bromine atom, iodine atom) , nitro, cyano, hydroxyl, lower cycloalkyl optionally substituted with a halogen atom (e.g.
  • alkyanoyl e.g. acetyl, propionyl etc.
  • alkoxycarbonyl e.g. methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, butoxycarbonyl etc.
  • carbamoyl e.g. methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, butoxycarbonyl etc.
  • thiocarbamoyl mono-or di- (lower alkyl) carbamoyl (e.g.
  • arylcarbamoyl e.g: phenylcarbamoyl, naphthylcarbamoyl etc.
  • aryl e.g. phenyl, naphthyl etc.
  • aryloxy e.g. phenyloxy, naphthyloxy etc.
  • alkylcarbonylamino optionally substituted with a halogen atorr ⁇ (e . g. acetylamino, trifluoroacetylamino etc.), lower alkylthio (e.g. methylthio etc.), lower alkylsulfinyl (e.g. methylsulfinyl etc.), lower alkylsulfonyl (e.g.
  • a halogen atorr ⁇ e . acetylamino, trifluoroacetylamino etc.
  • lower alkylthio e.g. methylthio etc.
  • lower alkylsulfinyl e.g. methylsulfinyl etc.
  • lower alkylsulfonyl e.g.
  • arylthio e.g. phenylthio
  • arylsulfinyl e.g. phenylsulfinyl, naphthylsulfinyl etc.
  • arylsulfonyl e.g. phenylsulfonyl, naphthylsulfonyl etc.
  • Preferable examples of the "lower alkynyl group" in the “lower alkynyl group optionally substituted with one or more substituents” represented by R 1 include ethynyl, 2- propynyl, 1-propynyl, 2-butynyl, 3-butynyl, 3-pentynyl, 3- hexynyl and the like, and
  • the "substituent" of the "one or more substitutents" in the "lower alkynyl group optionally substituted with one or more substituents” include a halogen atom (fluorine atom, chlorine atom, bromine atom, iodine atom) , nitro, cyano, hydroxyl, lower cycloalkyl optionally substituted with a halogen atom (e.g. cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl etc.), lower alkoxy (e.g.
  • amino, mono- or di- (lower alkyl) amino e.g. methylamino; ethylamino, dimethylamino, diethylamino etc.
  • carboxyl e.g. acetyl, propionyl etc.
  • lower alkoxycarbonyl e.g. methoxycarbonyl, ethoxycarbonyl, propoxycarbony
  • carbamoyl e.g. methylcarbamoyl,
  • arylcarbamoyl e.g. phenylcarbamoyl, naphthylcarbamoyl etc.
  • aryl e.g. phenyl, naphthylcarbamoyl etc.
  • aryl e.g. phenyl, naphthyl etc.
  • aryloxy e.g. phenyloxy, naphthyloxy etc.
  • lower alkylcarbonylamino optionally substituted with a halogen atom e.g.
  • acetylamino trifluoroacetylamino etc.
  • lower alkylthio e.g. methylthio etc.
  • lower alkylsulfinyl e.g.
  • arylthio e.g. phenylthio
  • arylsulfinyl e.g. phenylsulfinyl, naphthylsulfinyl etc.
  • arylsulfonyl e.g. phenylsulfonyl, naphthylsulfonyl etc.
  • R 1 substituents represented by R 1
  • the "substituent" of the "one or more substitutents" in the "lower cycloalkyl group optionally substituted with one or more substituents” include a halogen atom (fluorine atom, chlorine atom, bromine atom, iodine atom) , nitro, cyano, hydroxyl, lower alkyl optionally substituted with a halogen atom (e.g.
  • carbamoyl e.g. methylcarbamoyl,
  • arylcarbamoyl e.g. phenylcarbamoyl, naphthylcarbamoyl etc.
  • aryl e.g. phenyl, naphthylcarbamoyl etc.
  • aryl e.g. phenyl, naphthyl etc.
  • aryloxy e.g. phenyloxy, naphthyloxy etc.
  • lower alkylcarbonylamino optionally substituted with a halogen atom
  • acetylamino trifluoroacetylamino etc.
  • lower alkylthio e.g. methylthio etc.
  • lower alkylsulfinyl e.g.
  • arylthio e.g. phenylthio
  • arylsulfinyl e.g. phenylsulfinyl, naphthylsulfinyl etc.
  • arylsulfonyl e.g. phenylsulfonyl, naphthylsulfonyl etc.
  • aryl lower alkyl group in the “aryl lower alkyl group optionally substituted with one or more substituents” represented by R 1
  • substituents include benzyl, naphthylmethyl, anthracenylmethyl group and the like
  • substituted examples of the "substituent" of the "one or more substitutents" in the "aryl lower alkyl group optionally substituted with one or more substituents” include a halogen atom (fluorine atom, chlorine atom, bromine atom, iodine atom), nitro, cyano, hydroxyl, lower alkyl substituted with a halogen atom (e.g.
  • carbamoyl thiocarbamoyl, mono- or di- (lower alkyl) carbamoyl (e.g. methylcarbamoyl,
  • arylthio e.g. phenylthio
  • arylsulfinyl e.g. phenylsulfinyl, naphthylsulfinyl etc.
  • arylsulfonyl e.g. phenylsulfonyl, naphthylsulfonyl etc.
  • aryl group in the "aryl group optionally substituted with one or more substituents” represented by R 1 include phenyl, mesityl, xylyl, tolyl, naphthyl, anthracenyl, indanyl, biphenyl and the like, and preferable examples of the "substituent" of the "one or more substitutents" in the "aryl group optionally substituted with one or more substituents” include a halogen atom (fluorine atom, chlorine atom, bromine atom, iodine atom) , nitro, cyano, hydroxyl, lower alkyl
  • halogen atom e.g. chloromethyl
  • cycloalkyl optionally substituted with a halogen atom (e.g. cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl etc.), lower alkoxy (e.g. methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, pentyloxy, hexyloxy etc.), amino, mono- or di- (lower alkyl) amino (e.g. methylamino, ethylamino, dimethylamino, diethylamino etc.), carboxyl, lower alkanoyl (e.g. acetyl, propionyl etc.), lower alkoxycarbonyl (e.g. methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl,
  • a halogen atom e.g. cyclopropyl, cyclobutyl, cyclopentyl, cyclohexy
  • carbamoyl e.g. methylcarbamoyl,
  • arylcarbamoyl e.g. phenylcarbamoyl, naphthylcarbamoyl etc.
  • aryloxy e.g. phenyloxy, naphthyloxy etc.
  • lower alkylcarbonylamino optionally substituted with a halogen atom (e.g. acetylamino, trifluoroacetylamino etc.), lower alkylthio (e.g. methylthio etc.), lower alkylsulfinyl (e.g. methylsulfinyl etc.), lower alkylsulfonyl (e.g.
  • arylthio e.g. phenylthio
  • arylsulfinyl e.g. phenylsulfinyl, naphthylsulfinyl etc.
  • arylsulfonyl e.g. phenylsulfonyl, naphth ' ylsulfonyl etc.
  • Preferable example of the "lower alkoxy lower alkyl group" in the “lower alkoxy lower alkyl group optionally substituted with one or more substituents” represented by R 1 include methoxymethyl, ethoxymethyl, 2-methoxyethyl, 2- ethoxyethyl, 3-methoxypropyl, 3-ethoxypropyl, 4- methoxybutyl, 4-ethoxybutyl, 5-methoxypentyl, 5- ethoxypentyl, ⁇ -methoxyhexyl, 6-ethoxyhexyl and the like, and
  • substituents of the "one or more substituents" in the "lower alkoxy lower alkyl group optionally substituted with one or more substituents” include a halogen atom (fluorine atom, chlorine atom, bromine atom, iodine atom) , nitro, cyano, lower cycloalkyl optionally substituted with a halogen atom (e.g.
  • lower alkoxycarbonyl e.g. methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl
  • carbamoyl e.g. methylcarbamoyl,
  • arylcarbamoyl ethylcarbamoyl, dimethylcarbamoyl, diethylcarbamoyl etc.
  • arylcarbamoyl e. g . phenylcarbamoyl, naphthylcarbamoyl etc.
  • aryl e.g. phenyl, napthyl etc.
  • aryloxy e.g.
  • acetylamino trifluoroacetylamino etc.
  • lower alkylthio e.g. methylthio etc.
  • lower alkylsulfinyl e.g.
  • arylthio e.g. phenylthio
  • arylsulfinyl e.g. phenylsulfinyl, naphthylsulfinyl etc.
  • arylsulfonyl e.g. phenylsulfonyl, naphthylsulfonyl etc.
  • preferable examples of the "substituent" of the "one or more substituents" in the "aryloxy lower alkyl group optionally substituted with one or more substituents” include a halogen atom (fluorine atom, chlorine atom, bromine atom, iodine atom) , nitro, cyano, hydroxyl, lower cycloalkyl optionally substituted with a halogen atom (e.g. cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl etc.), lower alkyl substituted with a halogen atom (e.g.
  • alkoxycarbonyl e.g. methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, butoxycarbonyl etc.
  • carbamoyl e.g. methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, butoxycarbonyl etc.
  • thiocarbamoyl mono- or di- (lower alkyl) carbamoyl (e.g.
  • arylcarbamoyl e.g. phenylcarbamoyl, naphthylcarbamoyl etc.
  • aryloxy e.g. phenyloxy
  • lower alkylcarbonylamino substituted with a halogen atom e.g. acetylamino, trifluoroacetylamino etc.
  • lower alkylthio e.g. methylthio etc.
  • alkylsulfinyl e.g. methylsulfinyl etc.
  • alkylsulfonyl e.g. methylsulfonyl etc.
  • arylthio e.g. phenylthio, naphthylthio etc.
  • arylsulfinyl e.g. phenylsulfinyl, naphthylsulfinyl etc.
  • arylsulfonyl e.g. phenylsulfonyl, naphthylsulfonyl etc.
  • the "substituent" of the "one or more substituents" in the "lower alkylthio lower alkyl group optionally substituted with one or more substituents” include a halogen atom (fluorine atom, chlorine atom, bromine atom, iodine atom) , nitro, cyano, hydroxyl, lower cycloalkyl optionally substituted with a halogen atom (e.g. cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl etc.), lower alkoxy (e.g.
  • amino, mono- or di- (lower alkyl) amino e.g. methylamino, ethylamino, dimethylamino, diethylamino etc.
  • carboxyl e.g. acetyl, propionyl etc.
  • lower alkoxycarbonyl e.g. methoxycarbonyl, ethoxycarbonyl, propoxycarbony
  • carbamoyl, thiocarbamoyl, mono- or di- (lower alkyl) carbamoyl e.g. methylcarbamoyl, ethylcarbamoyl, dimethylcarbamoyl, diethylcarbamoyl etc.
  • arylcarbamoyl e.g. phenylcarbamoyl, nap'hthylcarbamoyl etc.
  • aryl e.g. phenyl, naphthyl etc.
  • aryloxy e.g. phenyloxy, naphthyloxy etc.
  • lower alkylcarbonylamino optionally substituted with a halogen atom
  • acetyl'amino, trifluoroacetylamino etc. lower alkylthio (e.g. methylthio etc.), lower alkylsulfinyl (e.g.
  • arylthio e.g. phenylthio
  • arylsulfinyl e.g. phenylsulfinyl, naphthylsulfinyl etc.
  • arylsulfonyl e.g. phenylsulfonyl, naphthylsulfonyl etc.
  • lower alkylsulfinyl lower alkyl group in the “lower alkylsulfinyl lower alkyl group optionally substituted with one or more substituents” represented by R 1 include methylsulfinylmethyl,
  • ethylsulfinylmethyl 2-methylsulfinylethyl, 2- ethylsulfinylethyl, 3-methylsulfinylpropyl, 3- ethylsulfinylpropyl, 4-methylsulfinylbutyl, 4- ethylsulfinylbutyl, 5-methylsulfinylpentyl, 5- ethylsulfinylpentyl, 6-methylsulfinylhexyl, 6- ethylsulfinylhexyl and the like, and
  • lower alkylsulfonyl lower alkyl group in the “lower alkylsulfonyl lower alkyl group optionally substituted with one or more substituents” represented by R 1 include methylsulfonylmethyl,
  • ethylsulfonylmethyl 2-methylsulfonylethyl, 2- ethylsulfonylethyl, 3-methylsulfonylpropyl, 3- ethylsulfonylpropyl, 4-methylsulfonylbutyl, 4- ethylsulfonylbutyl, 5-methylsulfonylpentyl, 5- ethylsulfonylpentyl, 6-methylsulfonylhexyl, 6- ethylsulfonylhexyl and the like, and
  • Preferable examples of the "lower alkylamino lower alkyl group" in the "mono or dilower alkylamino lower alkyl group optionally substituted with one or more substituents” represented by R 1 include methylaminomethyl, dimethylaminomethyl, methylethylaminomethyl, 2- (methylamino) ethyl, 2- (dimethylamino) ethyl, 3- (methylamino) propyl, 3- (dimethylamino) propyl, 3- (ethylamino) propyl, 4- (methylamino) butyl, A- (dimethylamino) butyl, 5- (methylamino) pentyl, 5- (dimethylamino) pentyl, 6- (methylamino) hexyl, 6- (dimethylamino) hexyl and the like, and
  • substituents of the "one or more substituents" in the "mono or dilower alkylamino lower alkyl group optionally substituted with one or more substituents” include a halogen atom (fluorine atom,
  • halogen atom e.g. cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl etc.
  • lower alkoxy e.g. methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, pentyloxy, hexyloxy etc.
  • amino, mono- or di- (lower alkyl) amino e.g.
  • thiocarbamoyl mono- or di- (lower alkyl) carbamoyl (e.g.
  • arylcarbamoyl e.g. phenylcarbamoyl, naphthylcarbamoyl etc.
  • aryl e.g. phenyl, naphthyl etc.
  • aryloxy e.g. phenyloxy, naphthyloxy etc.
  • alkylcarbonylamino optionally substituted with a halogen atom (e.g. acetylamino, trifluoroacetylamino etc.), lower alkylthio (e.g. methylthio etc.), lower alkylsulfinyl (e.g. methylsulfinyl etc.), lower alkylsulfonyl (e.g.
  • a halogen atom e.g. acetylamino, trifluoroacetylamino etc.
  • lower alkylthio e.g. methylthio etc.
  • lower alkylsulfinyl e.g. methylsulfinyl etc.
  • lower alkylsulfonyl e.g.
  • arylthio e.g. phenyltyhio
  • arylsulfinyl e.g. phenylsulfinyl, naphthylsulfinyl etc.
  • arylsulfonyl e. g. - phenylsulfonyl, naphthylsulfonyl etc.
  • Preferable examples of the "lower alkanoyl group" in the “lower alkanoyl group optionally substituted with one or more substitutents” represented by R 1 include acetyl, propionyl, butyryl, isobutyryl, valeryl, isovaleryl, pivaloyl, pentanoyl, hexanoyl and the like, and
  • optionally substituted with one or more substitutents include a halogen atom (fluorine atom, chlorine atom, bromine atom, iodine atom) , nitro, cyano, hydroxyl, lower cycloalkyl optionally substituted with a halogen atom (e.g. cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl etc.), lower alkoxy (e.g. methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, pentyloxy, hexyloxy etc.), amino, mono- or di- (lower alkyl) amino (e.g.
  • carbamoyl e.g. methylcarbamoyl,
  • arylcarbamoyl e.g. phenylcarbamoyl, naphthylcarbamoyl etc.
  • aryl e.g. phenyl, naphthylcarbamoyl etc.
  • aryl e.g. phenyl, naphthyl etc.
  • aryloxy e.g. phenyloxy, naphthyloxy etc.
  • lower alkylcarbonylamino optionally substituted with a halogen atom e.g.
  • acetylamino trifluoroacetylamino etc.
  • lower alkylthio e.g. methylthio etc.
  • lower alkylsulfinyl e.g.
  • arylthio e.g. phenylthio
  • arylsulfinyl e.g. phenylsulfinyl, naphthylsulfinyl etc.
  • arylsulfonyl e.g. phenylsulfonyl, naphthylsulfonyl etc.
  • lower alkanoyl group optionally substituted with one or more substituents include specifically, trifluoroacetyl, bromoacetyl, methylthioacetyl, methylsulfinylacetyl, and methylsulfonylacetyl .
  • propyloxycarbonyl isopropyloxycarbonyl, butoxycarbonyl, tert-butoxycarbonyl, pentyloxycarbonyl and hexyloxycarbonyl, and
  • the "substituent" of the "one or more substituents" in the "lower alkoxycarbonyl group optionally substituted with one or more substituents” include a halogen atom (fluorine atom, chlorine atom, bromine atom, iodine atom) , nitro, cyano, hydroxyl, lower cycloalkyl optionally substituted with a halogen atom (e.g. cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl etc.), lower alkoxy (e.g.
  • amino, mono- or di- (lower alkyl) amino e.g. methylamino, ethylamino, dimethylamino, diethylamino etc.
  • carboxyl e.g. acetyl, propionyl etc.
  • lower alkoxycarbonyl e.g. methoxycarbonyl, ethoxycarbonyl, propoxycarbony
  • carbamoyl e.g. methylcarbamoyl,
  • arylcarbamoyl e.g. phenylcarbamoyl, naphthylcarbamoyl etc.
  • aryloxy e.g. phenyloxy, naphthyloxy etc.
  • lower alkylcarbonylamino optionally substituted with a halogen atom (e.g. acetylamino, trifluoroacetylamino etc.), lower alkylthio (e.g. methylthio etc.), lower alkylsulfinyl (e.g. methylsulfinyl etc.), lower alkylsulfonyl (e.g.
  • arylthio e.g. phenylthio, naphthylthio etc.
  • arylsulfinyl e.g. phenylsulfinyl, naphthylsulfinyl etc.
  • arylsulfonyl e.'g. phenylsulfonyl, naphthylsulfonyl etc.
  • aryloxycarbonyl group in the “aryloxycarbonyl group optionally substituted with one or more substituents” represented by R 1 include
  • substituents include a halogen atom (fluorine atom, chlorine atom, bromine atom, iodine atom) , nitro, cyano, hydroxyl, lower alkyl substituted with a halogen atom (e.g.
  • cyclobutyl, cyclopentyl, cyclohexyl etc. lower alkoxy (e.g. methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, pentyloxy, hexyloxy etc. ) , amino, mono- or di- ( lower alkyl) amino (e.g. methylamino, ethylamino,
  • carbamoyl e.g. methylcarbamoyl,
  • arylcarbamoyl e.g. phenylcarbamoyl, naphthylcarbamoyl etc.
  • aryloxy e.g. phenyloxy, naphthyloxy etc.
  • lower alkylcarbonylamino optionally substituted with a halogen atom (e.g. acetylamino, trifluoroacetylamino etc.), lower alkylthio (e.g. methylthio etc.), lower alkylsulfinyl (e.g. methylsulfinyl etc.), lower alkylsulfonyl (e.g.
  • arylthio e.g. phenylthio
  • arylsulfinyl e.g. phenylsulfinyl, naphthylsulfinyl etc.
  • arylsulfonyl e.g. phenylsulfonyl, naphthylsulfonyl etc.
  • substituents of the "one or more substituents" in the "aryl lower alkoxycarbonyl group optionally substituted with one or more substituents” include a halogen atom (fluorine atom, chlorine atom, bromine atom, iodine atom) , nitro, cyano, hydroxyl, lower alkyl substituted with a halogen atom (e.g.
  • cycloalkyl optionally substituted with a halogen atom (e.g. cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl etc.), lower alkoxy (e.g. methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, pentyloxy, hexyloxy etc.), amino, mono- or di- (lower alkyl) amino (e.g. methylamino, ethylamino, dimethylamino, diethylamino etc.), carboxyl, lower alkanoyl (e.g. acetyl, propionyl etc.), lower alkoxycarbonyl (e.g. methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl,
  • a halogen atom e.g. cyclopropyl, cyclobutyl, cyclopentyl, cyclohexy
  • carbamoyl e.g. methylcarbamoyl,
  • arylcarbamoyl e.g. phenylcarbamoyl, naphthylcarbamoyl etc.
  • aryloxy ' e.g. phenyloxy, naphthyloxy etc.
  • lower alkylcarbonylamino optionally substituted with a halogen atom (e.g. acetylamino, trifluoroacetylamino etc.), lower alkylthio (e.g. methylthio etc.), lower alkylsulfinyl (e.g. methylsulfinyl etc.), lower alkylsulfonyl (e.g.
  • arylthio e.g. phenylthio
  • arylsulfinyl e.g. phenylsulfinyl, naphthylsulfinyl etc.
  • arylsulfonyl e.g. phenylsulfonyl, naphthylsulfonyl etc.
  • substituents of the "one or more substituent" in the "carbamoyl group optionally substituted with one or more substituents” represented by R 1 include lower alkyl optionally substituted with a halogen atom (e.g.
  • alkoxycarbonyl e.g. methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, butoxycarbonyl etc.
  • aryl e.g. phenyl, naphthyl etc.
  • preferable examples' of the "carbamoyl group optionally substituted with one or more substituents" include a dimethylcarbamoyl group.
  • R 1 optionally substituted with one or more substituents represented by R 1 include lower alkyl optionally substituted with one or more substituents represented by R 1 include lower alkyl optionally substituted with one or more substituents represented by R 1 include lower alkyl optionally substituted with one or more substituents represented by R 1 include lower alkyl optionally substituted with one or more substituents represented by R 1 include lower alkyl optionally substituted with one or more substituents represented by R 1 include lower alkyl optionally
  • halogen atom e.g. methyl, ethyl, 2- bromoethyl, 2, 2, 2-trifluoroethyl, propyl, 3,3,3- trifluoropropyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, 4 , 4 , 4-trifluorobutyl, pentyl, isopentyl, neopentyl, 5, 5, 5-trifluoropentyl, hexyl, 6,6,6- trifluorohexyl etc.), lower cycloalkyl optionally
  • halogen atom e.g. cyclopropyl
  • lower alkanoyl e.g. acetyl, ⁇ propionyl etc.
  • lower alkoxycarbonyl e.g. methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl
  • aryl e.g. phenyl, naphthyl etc.
  • the "substituent" of the "one or more substituents" in the "lower alkoxyoxalyl group optionally substituted with one or more substituents” include a halogen atom (fluorine atom, chlorine aton, bromine atom, iodine atom) , nitro, cyano, hydroxyl, lower cycloalkyl optionally substituted with a halogen atom (e.g. cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, etc.), lower alkoxy (e.g.
  • amino, mono- or di- (lower alkyl) amino e.g. methylamino, ethylamino, dimethylamino, diethylamino etc.
  • carboxyl e.g. acetyl, propionyl etc.
  • lower alkoxycarbonyl e.g. methoxycarbonyl, ethoxycarbonyl, propoxycarbony
  • carbamoyl e.g. methylcarbamoyl,
  • arylcarbamoyl e.g. phenylcarbamoyl, naphthylcarbamoyl etc.
  • aryloxy e.g. phenyloxy, naphthyloxy etc.
  • lower alkylcarbonylamino optionally substituted with a halogen atom-, (e.g. acetylamino, trifluoroacetylamino etc.), lower alkylthio (e.g. methylthio etc.), lower alkylsulfinyl (e.g. methylsulfinyl etc.), lower alkylsulfonyl (e.g.
  • arylthio e.g. phenylthio
  • arylsulfinyl e.g. phenylsulfinyl, naphthyl sulfinyl etc.
  • arylsulfonyl e.g. phenylsulfonyl, naphthylsulfonyl etc.
  • aryl lower alkoxyoxalyl group in the "aryl lower alkoxyoxalyl group optionally substituted with one or more substituents” represented by R 1 include benzyloxyoxalyl and the like, and
  • substituents of the "one or more substituents" in the "aryl lower alkoxyoxalyl group optionally substituted with one or more substituents” include a halogen atom (fluorine atom, chlorine atom, bromine atom, iodine atom) , nitro, cyan ⁇ , hydroxyl, lower alkyl substituted with a halogen atom (e.g.
  • cycloalkyl group optionally substituted with a halogen atom (e.g. cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl etc.), lower alkoxy (e.g. methoxy, ethoxy, propoxy,
  • a halogen atom e.g. cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl etc.
  • lower alkoxy e.g. methoxy, ethoxy, propoxy
  • alkoxycarbonyl e.g. methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, butoxycarbonyl etc.
  • carbamoyl e.g. methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, butoxycarbonyl etc.
  • thiocarbamoyl mono- or di- (lower alkyl) carbamoyl (e.g.
  • arylcarbamoyl e.g. phenylcarbamoyl, naphthylcarbamoyl etc.
  • aryloxy e.g. phenyloxy
  • lower alkylcarbonylamino optionally substituted with a halogen atom (e.g. acetylamino,
  • methylthio etc. lower alkylsulfinyl (e.g. methylsulfinyl etc.), lower alkylsulfonyl (e.g. methylsulfonyl etc.), arylthio (e.g. phenylthio, naphthylthio etc.), arylsulfinyl (e.g. phenylsulfinyl, naphthylsulfinyl etc.), arylsulfonyl (e.g. phenylsulfonyl, naphthylsulfonyl etc.) and the like.
  • arylthio e.g. phenylthio, naphthylthio etc.
  • arylsulfinyl e.g. phenylsulfinyl, naphthylsulfinyl etc.
  • arylsulfonyl e.g. pheny
  • halogen atom fluorine atom, chlorine atom, bromine atom, iodine atom
  • nitro, cyano, hydroxyl lower alkyl substituted with a halogen atom (e.g. chloromethyl, difluoromethyl, trichloromethyl, trifluoromethyl, 2- bromoethyl, 2, 2, 2-trifluoroethyl, pentafluoroethyl, 3,3,3- trifluoropropyl, 4 , 4 , 4-trifluorobutyl, 5,5,5- trifluoropentyl, 6, 6, 6-trifluorohexyl etc.), lower
  • cycloalkyl group optionally substituted with a halogen atom (e.g. cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl etc.), lower alkoxy (e.g. methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, pentyloxy, hexyloxy etc.), amino, mono- or di- (lower alkyl) amino (e.g. methylamino, ethylamino, dimethylamino, diethylamino etc.), carboxyl, lower alkanoyl (e.g. acetyl, propionyl etc.), lower
  • alkoxycarbonyl e.g. methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, butoxycarbonyl etc.
  • carbamoyl e.g. methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, butoxycarbonyl etc.
  • thiocarbamoyl mono- or di- (lower alkyl) ' carbamoyl (e.g.
  • arylcarbamoyl e.g. phenylcarbamoyl, naphthylcarbamoyl etc.
  • aryloxy e.g. phenyloxy
  • lower alkylcarbonylamino optionally substituted with a halogen atom (e.g. acetylamino,
  • methylthio etc. lower alkylsulfinyl (e.g. methylsulfinyl etc.), lower alkylsulfonyl (e.g. methylsulfonyl etc.), arylthio (e.g. phenylthio, naphthylthio etc.), arylsulfinyl (e.g: phenylsulfinyl, naphthylsulfinyl etc.), arylsulfonyl (e.g. phenylsulfonyl, naphthylsulfonyl etc.) and the like.
  • arylthio e.g. phenylthio, naphthylthio etc.
  • arylsulfinyl e.g: phenylsulfinyl, naphthylsulfinyl etc.
  • arylsulfonyl e.g. pheny
  • halogen atom e.g. methyl, chloromethyl, difluoromethyl, trichloromethyl, trifluoromethyl, ethyl, 2-bromoethyl,
  • lower cycloalkyl optionally
  • halogen atom e.g. cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl etc.
  • lower alkanoyl e.g. acetyl, propionyl etc.
  • lower aUcoxycarbonyl e.g. methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl
  • aryl e.g. phenyl, naphthyl etc.
  • Preferable examples of the "lower alkoxy group" in the “lower alkoxy group optionally substituted with one or more substituents” represented by R 1 include methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, tert-butoxy, pentyloxy, tert-pentyloxy, neo-pentyloxy, hexyloxy,
  • arylcarbamoyl e.g. phenylcarbamoyl, naphthylcarbamoyl etc.
  • aryloxy e.g. phenyloxy, naphthyloxy etc.
  • lower alkylcarbonylamino optionally substituted with a halogen atom (e.g. acetylamino, trifluoroacetylamino etc.), lower alkylthio (e.g. methylthio etc.), lower alkylsulfinyl (e.g. methylsulfinyl etc.), lower alkylsulfonyl (e.g.
  • arylthio e.g. phenylthio
  • arylsulfinyl e.g. phenylsulfinyl, naphthylsulfinyl etc.
  • arylsulfonyl e.g. phenylsulfonyl, naphthylsulfonyl etc.
  • aryloxy group in the "aryloxy group optionally substituted with one or more substituents” represented by R 1 include phenoxy,
  • substituents of the "one or more substituents" in the "aryloxy group optionally substituted with one or more substituents” include a halogen atom (fluorine atom, chlorine atom, bromine atom, iodine atom) , nitro, cyano, hydroxyl, lower cycloalkyl optionally substituted with a halogen atom (e.g.
  • halogen atom e.g. chloromethyl, difluoromethyl, trichloromethyl, trifluoromethyl, 2-bromoethyl, 2, 2, 2-trifluoroethyl,
  • pentafluoroethyl 3, 3, 3-trifluoropropyl, 4,4,4- trifluorobutyl, 5, 5, 5-trifluoropentyl, hexyl, 6,6,6- trifluorohexyl etc.
  • lower alkoxy e.g. methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, pentyloxy, hexyloxy etc.
  • amino, mono- or di- (lower alkyl) amino e.g.
  • thiocarbamoyl mono- or di- (lower alkyl) carbamoyl (e.g.
  • arylcarbamoyl e.g. phenylcarbamoyl, naphthylcarbamoyl etc.
  • aryloxy e.g. phenyloxy
  • lower alkylcarbonylamino optionally substituted with a halogen atom (e.g. acetylamino,
  • methylthio etc. lower alkylsulfinyl (e.g. methylsulfinyl etc.), lower alkylsulfonyl (e.g. methylsulfonyl etc.), arylthio (e.g. phenylthio, naphthylthio etc.), arylsulfinyl (e.g. phenylsulfinyl, naphthylsulfinyl etc.), arylsulfonyl (e.g. phenylsulfonyl, naphthylsulfonyl etc.) and the like.
  • arylthio e.g. phenylthio, naphthylthio etc.
  • arylsulfinyl e.g. phenylsulfinyl, naphthylsulfinyl etc.
  • arylsulfonyl e.g. pheny
  • aryl lower alkoxy group in the "aryl lower alkoxy group optionally substituted with one or more substituents” represented by R 1 include
  • substituents of the "one or more substituents" in the "aryl lower alkoxy group optionally substituted with one or more substituents” include a halogen atom (fluorine atom, chlorine atom, bromine atom, iodine atom) , nitro, cyano, hydroxyl, lower alkyl substituted with a halogen atom (e.g.
  • cycloalkyl optionally substituted with a halogen atom (e.g. cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl etc.), lower alkoxy (e.g. methoxy; ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, pentyloxy, hexyloxy etc.), amino, mono- or di- (lower alkyl) amino (e.g. methylamino, ethylamino, dimethylamino, diethylamino etc.), carboxyl, lower alkanoyl (e.g. acetyl, propionyl etc.), lower alkoxycarbonyl (e.g. methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl,
  • a halogen atom e.g. cyclopropyl, cyclobutyl, cyclopentyl, cyclohexy
  • carbamoyl e.g. methylcarbamoyl,
  • arylcarbamoyl e.g. phenylcarbamoyl, naphthylcarbamoyl etc.
  • aryloxy e.g. phenyloxy, naphthyloxy etc.
  • lower alkylcarbonylamino optionally substituted with a halogen atom (e.g. acetylamino, trifluoroacetylamino etc.), lower alkylthio (e.g. methylthio etc.), lower alkylsulfinyl (e.g. methylsulfinyl etc.), lower alkylsulfonyl (e.g.
  • arylthio e.g. phenylthio
  • arylsulfinyl e.g. phenylsulfinyl, naphthylsulfinyl etc.
  • arylsulfonyl e. g. , phenylsulfonyl, naphthylsulfonyl etc.
  • alkoxycarbonyl e.g. methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, butoxycarbonyl etc.
  • carbamoyl e.g. methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, butoxycarbonyl etc.
  • thiocarbamoyl mono- or di- (lower alkyl) carbamoyl (e.g.
  • methylcarbamoyl ethylcarbamoyl, dimethylcarbamoyl, diethylcarbamoyl etc.
  • arylcarbamoyl e.g. phenylcarbamoyl, naphthylcarbamoyl etc.
  • aryl e.g. pheriyl, naphthyl etc.
  • heterocyclic group in the “heterocyclic group optionally substituted with one or more substituents” * represented by R 1 include an "aromatic
  • aromatic monocyclic heterocyclic group examples include 5-membered aromatic monocyclic heterocyclic groups such as 2-furyl, 3-furyl, 2-thienyl, 3-thienyl, 2-pyrrolyl, 3-pyrrolyl, 2-oxazolyl, 4-oxazolyl, 5-oxazolyl, 3- isoxazolyl, 4-isoxazolyl, 5-isoxazolyl, 2-thiazolyl, 4- thiazolyl, 5-thiazolyl, 3-isothiazolyl, 4-isothiazolyl, 5- isothiazolyl, 2-imidazolyl, 4-imidazolyl, 5-imidazolyl, 3- pyrazolyl, 4-pyrazolyl, 5-pyrazolyl, 1, 2, 3-oxadiazol-4-yl, 1, 2, 3-oxadiazol-5-yl, 1, 2, 4-oxadiazol-5-yl, 1,2,4- oxadiazol-3-yl, 1, 3, 4-oxadiazol-2-yl, furazanyl,
  • 6-membered aromatic monocyclic heterocyclic groups such as 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyrimidinyl, 4- pyrimidinyl, 5-pyrimidinyl, 3-pyridazinyl, 4-pyridazinyl, 2-pyrazinyl, 1, 2 , 4-triazin-3-yl, 1, 2, 4-triazin-5-yl, 1,2,4- triazin-6-yl, 1, 3, 5-triazin-2-yl and the like, and
  • halogen atom fluorine atom, chlorine atom, bromine atom, iodine atom
  • lower alkyl optionally substituted with a halogen atom
  • a halogen atom e.g. methyl, chloromethyl, dichloromethyl, trifluoromethyl, ethyl, 2, 2, 2-trifluoromethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, hexyl etc.
  • lower cycloalkyl e.g. cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl etc.
  • aryl lower alkyl e.g.
  • arylcarbonyloxy e.g. benzoyloxy, naphthoyloxy etc.
  • carboxyl lower alkoxycarbonyl (e.g. methoxycarbonyl, ethoxycarbonyl, propyloxycarbonyl, isopropyloxycarbonyl, butoxycarbonyl, isobutoxycarbonyl, tert-butoxycarbonyl etc.), aryl lower alkoxycarbonyl (e.g. benzyloxycarbonyl etc.), carbamoyl, amino, mono- or di- (lower alkyl) amino (e.g. mono (lower alkyl) amino such as methylamino,
  • diethylamino, dipropylamino, diisopropylamino, dibutylamino and methylethylamino a 3- to 6- membered cyclic amino group (e.g. aziridinyl, azetidinyl, pyrrodinyl, pyrrolinyl, pyrrolyl, imidazolyl, pyrazolyl, imidazolidinyl, piperidyl, morpholinyl, dihydropyridyl, N-methylpiperazinyl, N- ethylpiperazinyl etc.), nitro, cyano, mono or di (lower alkyl) sulfamoyl group (e.g.
  • lower alkyl sulfamoyl such as N-methylsulfamoyl, N-ethylsulfamoyl, N-propylsulfamoyl, N-is ⁇ propylsulfamoyl, and N-butylsulfamoyl, as well as di (lower alkyl) sulfamoyl such as N, N-dimethylsulfamoyl, N, N-diethylsulfamoyl, N, N, -dipropylsulfamoyl, and N, N- dibutylsulfamoyl) , lower alkylthio (e.g.
  • arylsulfinyl e.g. phenylsulfinyl, naphthylsulfinyl etc.
  • lower alkylsulfonyl e.g.
  • arylsulfonyl e.g. phenylsulfonyl, naphthylsulfonyl etc.
  • Examples of the "lower alkylene” in the “lower alkylene optionally substituted with one or more halogen atoms” represented by R 2 include methylene, ethylene, trimethylene, hexamethylene, pentamethylene, and
  • hexamethylene preferably a "C1-C6 alkylene group” such as methylene, ethylene, trimethylene, and hexamethylene, and examples “ of the "halogen atom” of the “one or more halogen atoms" in the "lower alkylene optionally
  • substituted with one or more halogen atoms include a fluorine atom, a chlorine atom, a bromine atom, and an iodine atom.
  • Preferable examples of the "lower alkanoyl group" in the '"lower alkanoyl group optionally substituted with one or more substituents” represented by R 3 include acetyl, propionyl, butyryl, isobutyryl, valeryl, isovaleryl, pivaloyl, pentanoyl, hexanoyl and the like, and
  • substituents include a halogen atom (fluorine atom, chlorine atom, bromine atom, iodine atom) , nitro, cyano, hydroxyl, lower alkoxy (e.g. methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, pentyloxy, hexyloxy etc.), amino, mono- or di- (lower alkyl) amino (e.g. methylamino, ethylamino,
  • carbamoyl e.g. methylcarbamoyl,
  • arylcarbamoyl e.g. phenylcarbamoyl, naphthylcarbamoyl etc.
  • aryl e.g. phenyl, naphtyl etc.
  • aryloxy e.g. phenyloxy, naphthyloxy etc.
  • lower alkylcarbonylamino optionally substituted with a halogen atom
  • acetylamino trifluoroacetylamino etc.
  • lower alkylthio e.g. methylthio etc.
  • lower alkylsulfinyl e.g.
  • arylthio e.g. phenylthio
  • arylsulfinyl e.g. phenylsulfinyl, naphthylsulfinyl etc.
  • arylsulfonyl e.g. phenylsulfonyl, naphthylsulfonyl etc.
  • Examples of the "C1-C3 alkyl group" in the “C1-C3 alkyl group optionally substituted with one or more substituents” represented by R 3 , R 4 , R 5 and R 6 include methyl, ethyl, n-propyl, and isopropyl, and
  • substituents in the "one or more substituents” in the "C1-C3 alkyl group optionally substituted with one or more substituents” include a halogen atom (fluorine atom, chlorine atom, bromine atom, iodine atom), nitro, cyano, hydroxyl, lower alkoxy (e.g. methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, pentyloxy, hexyloxy etc.), amino, mono- or di- (lower
  • alkyl amino (e.g. methylamino, ethylamino, dimethylamino, diethylamino etc.), carboxyl, lower alkanoyl (e.g. acetyl, propionyl etc.), lower alkoxycarbonyl (e.g. methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, butoxycarbonyl etc.), carbamoyl, thiocarbamoyl, mono- or di- (lower
  • alkyl carbamoyl (e.g. methylcarbamoyl, ethylcarbamoyl, dimethylcarbamoyl, diethylcarbamoyl etc.),- arylcarbamoyl (e.g. phenylcarbamoyl, naphthylcarbamoyl etc.), aryloxy (e.g. phenyloxy, naphthyloxy etc.), lower
  • alkylcarbonylamino optionally substituted with a halogen atomMe.g. acetylamino, trifluoroacetylamino etc.
  • lower alkylthio e.g. methylthio etc.
  • lower alkylsulfinyl e.g. methylsulfinyl etc.
  • lower alkylsulfonyl e.g.
  • arylthio e.g. phenylthio
  • arylsulfinyl e.g. phenylsulfinyl, naphthylsulfinyl etc.
  • arylsulfonyl e.g. phenylsulfonyl, naphthylsulfonyl etc.
  • Preferable examples of the "lower alkenyl group" in the “lower alkenyl group optionally substituted with one or more substituents” represented by R 3 , R 4 , R 5 and R 6 include vinyl, allyl, isopropenyl, isobutenyl, 1-methylallyl, 2- pentenyl, 2-hexenyl and the like, and
  • preferable examples of the "substituent" in the "one or more substituents” in the “lower alkenyl group optionally substituted with one or more substituents” include a halogen atom (fluorine atom, chlorine atom, bromine atom, iodine atom) , nitro, cyano, hydroxyl, lower alkoxy (e.g. methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, pentyloxy, hexyloxy etc.), amino, mono- or di- (lower alkyl) amino (e.g. methylamino, ethylamino,
  • carbamoyl e.g. methylcarbamoyl,
  • arylcarbamoyl e.g. phenylcarbamoyl, naphthylcarbamoyl etc.
  • aryl e.g. phenyl, naphthylcarbamoyl etc.
  • aryl e.g. phenyl, naphthyl etc.
  • aryloxy e.g. phenyloxy, naphthyloxy etc.
  • lower alkylcarbonylamino optionally substituted with a halogen atom e.g.
  • acetylamino trifluoroacetylamino etc.
  • lower alkylthio e.g. methylthio etc.
  • lower alkylsulfinyl e.g.
  • arylthio e.g. phenylthio
  • arylsulfinyl e.g. phenylsulfinyl, naphthylsulfinyl etc.
  • arylsulfonyl e.g. phenylsulfonyl, naphthylsulfonyl etc.
  • Preferable examples of the "lower alkynyl group" in the “alkynyl group optionally substituted with one or more substituents” represented by R 3 , R 4 , R 5 and R 6 include ethynyl, 2-propynyl, 1-propynyl, 2-butyriyl, 3-butynyl, 3- pentynyl, 3-hexynyl and the like, and
  • halogen atom fluorine atom, chlorine atom, bromine atom, iodine atom
  • nitro cyano
  • hydroxyl lower alkoxy (e.g. methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, pentyloxy, hexyloxy etc.), amino, mono- or di- (lower
  • alkyl amino (e.g. methylamino, ethylamino, dimethylamino, diethylamino etc.), carboxyl, lower alkanoyl (e.g. acetyl, propionyl etc.), lower alkoxycarbonyl (e.g. methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, butoxycarbonyl etc.), carbamoyl, thiocarbamoyl, mono- or di- (lower
  • alkyl carbamoyl (e.g. methylcarbamoyl, ethylcarbamoyl, dimethylcarbamoyl, diethylcarbamoyl etc.), arylcarbamoyl (e.g. phenylcarbamoyl, naphthylcarbamoyl etc.), aryl (e.g. phenyl, naphthyl etc.), aryloxy (e.g. phenyloxy,
  • lower alkylcarbonylamino optionally substituted with a halogen atom (e.g. acetylamino,
  • methylthio etc. lower alkylsulfinyl (e.g. methylsulfinyl etc.), lower alkylsulfonyl (e.g. methylsulfonyl etc.), arylthio (e.g. phenylthio, naphthylthio etc.), arylsulfinyl (e.g. phenylsulfinyl, naphthylsulfinyl etc.), arylsulfonyl (e.g. phenylsulfonyl, naphthylsulfonyl e'tc.) and the like.
  • arylthio e.g. phenylthio, naphthylthio etc.
  • arylsulfinyl e.g. phenylsulfinyl, naphthylsulfinyl etc.
  • arylsulfonyl e.g
  • aryl group in the "aryl group optionally substituted with one or more substituents” represented by R 3 , R 4 , R 5 and R 6 include phenyl, mesityl, xylyl, tolyl, " naphthyl, anthracenyl and the like, and
  • substituted with one or more substituents include a halogen atom (fluorine atom, chlorine atom, bromine atom, iodine atom) , nitro, cyano, hydroxyl, lower alkyl
  • halogen atom e.g. chloromethyl, difluoromethyl, trifluoromethyl, trifluoromethyl, 2- bromoethyl, 2, 2 , 2-trifluoroethyl, pentafluoroethyl, 3,3,3- trifluoropropyl, 4 , 4 , 4-trifluorobutyl, 5,5,5- trifluoropentyl, 6, 6, ⁇ -trifluorohexyl etc.), lower alkoxy (e.g.
  • carbamoyl e.g. methylcarbamoyl,
  • arylcarbamoyl e.g. phenylcarbamoyl, naphthylcarbamoyl etc.
  • aryloxy e.g. phenyloxy, naphthy ⁇ oxy etc.
  • lower alkylcarbonylamino optionally substituted with a halogen atom (e.g. acetylamino, trifluoroacetylamino etc.), lower alkylthio (e.g. methylthio etc.), lower alkylsulfinyl (e.g. methylsulfinyl etc.), lower alkylsulfonyl (e.g.
  • arylthio e.g. phenylthio
  • arylsulfinyl e.g. phenylsulfinyl, naphthylsulfinyl etc.
  • arylsulfonyl e.g. phenylsulfonyl, naphthylsulfonyl etc.
  • aryl lower alkyl group in the “aryl lower alkyl group optionally substituted with one or more substituents” represented by R 3 , R 4 , R 5 and R 6 include benzyl, phenethyl and the like, and
  • substituents of the "one or more substituents" in the "aryl lower alkyl group optionally substituted with one or more substituents” include a halogen atom (fluorine atom, chlorine atom, bromine atom, iodine atom) , nitro, cyano, hydroxyl, lower alkyl substituted with a halogen atom (e.g.
  • carbamoyl e.g. methylcarbamoyl,
  • arylcarbamoyl e.g. phenylcarbamoyl, naphthylcarbamoyl etc.
  • aryloxy e.g. phenyloxy, naphtylocy etc.
  • lower alkylcarbonylamino optionally substituted with a halogen atom ⁇ (e.g. acetylamino, trifluoroacetylamino etc.), lower alkylthio (e.g. methylthio etc.), lower alkylsulfinyl (e.g. methylsulfinyl etc.), lower alkylsulfonyl (e.g.
  • arylthio e.g. phenylthio
  • arylsulfinyl e.g. phenylsulfinyl, naphthylsulfinyl etc.
  • arylsulfonyl e.g. phenylsulfonyl, naphthylsulfonyl etc.
  • R 5 and R 6 are taken together at the ends thereof to form together with the nitrogen atom a 3- to 7-membered nitrogen-containing heterocycle optionally having other nitrogen atom, oxygen atom or sulfur atom as a ring constituting atom
  • examples of the "R 5 and R 6 are taken together at the ends thereof to form together with the nitrogen atom a 3- to 7-membered nitrogen-containing heterocycle optionally having other nitrogen atom, oxygen atom or sulfur atom as a ring constituting atom” include a 1-pyrrolidinyl group, a piperidino group, a morpholino group, and a thiomorpholino group.
  • halogen atom represented by R 7 include a fluorine atom, a chlorine atom, a bromine atom, and an iodine atom.
  • Preferable examples of the "lower alkanoyl group" in the “lower alkanoyl group optionally substituted with one or more halogen atoms” represented by R 7 include acetyl, propionyl, butyryl, isobutyryl, pentanoyl, 2,2- dimethylpropionyl, hexanoyl and the like, and
  • halogen atom the aforementioned "halogen atom" can be mentioned.
  • lower alkoxycarbonyl group in the “lower alkoxycarbonyl group optionally substituted with one or more halogen atoms” represented by R 7 include methoxycarbonyl, ethoxycarbonyl,
  • propyloxycarbonyl isopropyloxycarbonyl, butoxycarbonyl, tert-butoxycarbonyl, pentyloxycarbonyl, hexyloxycarbonyl and the like, and
  • aryl group in the "aryl group optionally substituted with one or more halogen atoms” represented by R 7 include phenyl, 1-naphthyl, 2- naphthyl, biphenylyl, 2-anthracenyl and the like, and
  • halogen atom the aforementioned "halogen atom" can be mentioned.
  • halogen atom the aforementioned "halogen atom" can be mentioned.
  • arylcarbamoyl group in the “arylcarbamoyl group' optionally substituted with one or more halogen atoms" represented by R 7 include
  • phenylcarbamoyl 1-naphthylcarbamoyl, 2-naphthylcarbamoyl, biphenylylcarbamoyl, 2-anthracenylcarbamoyl and the like, and
  • halogen atom the aforementioned "halogen atom" can be mentioned.
  • Preferable examples of the "lower alkyl group" in the "carbamoyl group optionally substituted with one or more lower alkyl groups” represented by R 7 include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert- butyl, n-pentyl, sec-pentyl, isopentyl, neopentyl, n-hexyl, isohexyl and the like.
  • Preferable examples of the "lower alkyl group" in the "thiocarbamoyl group optionally substituted with one or more lower alkyl groups” represented by R 7 include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, sec-pentyl, isopentyl, neopentyl, n- hexyl, isohexyl and the like.
  • Preferable examples of the "lower alkyl group" in the "amino group optionally substituted with one or more lower alkyl groups” represented by R 7 include methyl, ethyl, n- propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, sec-pentyl, isopentyl, neopentyl, n-hexyl,
  • Preferable examples of the "lower alkyl group" in the “lower alkyl group optionally substituted with one or more halogen atoms” represented by R 7 include methyl, ethyl, n- propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, sec-pentyl, isopentyl, neopentyl, n-hexyl,
  • halogen atom the aforementioned "halogen atom" can be mentioned.
  • Preferable examples of the "lower alkoxy group" in the “lower alkoxy group optionally substituted with one or more halogen atoms” represented by R 7 include methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, 'tert-butoxy, pentyloxy, tert-pentyloxy, neo-pentyloxy, hexyloxy, isohexyloxy and the like, preferably methoxy, ethoxy, propoxy, butoxy, pentyloxy, hexyloxy, and isohexyloxy, and as the "halogen atom", the aforementioned "halogen atom" can be mentioned.
  • Preferable examples of the "lower alkoxy lower alkoxy group" in the “lower alkoxy lower alkoxy group optionally substituted with one or more halogen atoms" represented by R 7 include methoxymethoxy, ethoxymethoxy, 2-methoxymethoxy, 2-ethoxyethoxy, 3-methoxypropyloxy, 3-ethoxypropyloxy, 4- methoxybutyloxy, 4-ethoxybutyloxy, 5-methoxypentyloxy, 5- ethoxypentyloxy, 6-methoxyhexyloxy, 6-ethoxyhexyloxy and the like, and
  • halogen atom the aforementioned "halogen atom" can be mentioned.
  • Preferable examples of the "lower alkenyloxy group" in the “lower alkenyloxy group optionally substituted with one or more halogen atoms” represented by R 7 include vinyloxy, allyloxy, isopropynyloxy, isobutenyloxy, 1-methylallyloxy, 2-pentenyloxy, 2-hexenyloxy and the like, and
  • halogen atom the aforementioned "halogen atom" can be mentioned.
  • Preferable examples of the "lower alkynyloxy group" in the “lower alkynyloxy group optionally substituted with one or more halogen atoms” represented by R 7 include ethynyloxy, 2-propynyloxy, 1-propynyloxy, 2-butynyloxy, 3-butynyloxy, 3-pentynyloxy, 3-hexynyloxy, and the like, and
  • halogen atom the aforementioned "halogen atom" can be mentioned.
  • lower alkanoylamino group in the “lower alkanoylamino group optionally substituted with one or more halogen atoms” represented by R 7 include acetylamino, 2-methylpropionylamino, propionylamino,
  • butyrylamino isobutyrylamino, pentanoylamino, 2,2- dimethylpropionylamino, hexanoylamino and the like, and
  • halogen atom the aforementioned "halogen atom" can be mentioned.
  • halogen atom the aforementioned "halogen atom" can be mentioned.
  • halogen atom the aforementioned "halogen atom" can be mentioned.
  • Preferable examples of the "lower alkynylthio group" in the “lower alkynylthio group optionally substituted with one or more halogen atoms” represented by R 7 include 2- propynylthio, 1-propynylthio, 2-butynylthio, 3-butynylthio, 3-pentynylthio, 3-hexynylthio and the like, and
  • Preferable examples of the "lower alkylsulfinyl group" in the “lower alkylsulfinyl group optionally substituted with one or more halogen atoms” represented by R 7 include methylsulfinyl, ethylsulfinyl, n-propylsulfinyl,
  • halogen atom the aforementioned "halogen atom" can be mentioned.
  • Preferable examples of the "lower alkenylsulfinyl group" in the “lower alkenylsulfinyl group optionally substituted with one or more halogen atoms" represented by R 7 include allylsulfinyl, isopropenylsul ' finyl,
  • halogen atom the aforementioned "halogen atom" can be mentioned.
  • Preferable examples of the "lower alkynylsulfinyl group" in the “lower alkynylsulfinyl group. optionally substituted with one or more halogen atoms" represented by R 7 include 2-propynylsulfinyl, 1-propynylsulfinyl, 2- butynylsulfinyl, 3-butynylsulfinyl, 3-pentynylsulfinyl, 3- hexynylsulfinyl and the like, and
  • halogen atom the aforementioned "halogen atom" can be mentioned.
  • Preferable examples of the "lower alkylsulfonyl group" in the “lower alkylsulfonyl group optionally substituted with one or more halogen atoms” represented by R 7 include methylsulfonyl, ethylsulfonyl, n-propylsulfonyl,
  • halogen atom the aforementioned "halogen atom" can be mentioned.
  • Preferable examples of the "lower alkenylsulfonyl group" in the “lower alkenylsulfonyl group optionally substituted with one or more halogen atoms” represented by R 7 include allylsulfonyl, isopropenylsulfonyl,
  • halogen atom the aforementioned "halogen atom" can be mentioned.
  • Preferable examples of the "lower alkynylsulfonyl group" in the “lower alkynylsulfonyl group optionally substituted with one or more halogen atoms” represented by R 7 include 2-propynylsulfonyl, 1-propynylsulfonyl, 2- butynylsulfonyl, 3-butynylsulfonyl, 3-pentynylsulfonyl, 3- hexynylsulfonyl and the like, and
  • halogen atom the aforementioned "halogen atom" can be mentioned.
  • alkylthio group in the "lower alkoxy lower alkylthio group optionally substituted with one or more halogen atoms" represented by R 7 include methoxymethylthio,
  • ethoxymethylthio 2-methoxyethylthio, 2-ethoxyethylthio, 3- methoxypropylthio, 3-ethoxypropylthio, 4-methoxybutylthio, 4-ethoxybutylthio, 5-methoxypentylthio, 5-ethoxypentylthio, 6-methoxyhexylthio, 6-ethoxyhexylthio and the like, and
  • halogen atom the aforementioned "halogen atom” can be mentioned.
  • halogen atom which is a substituent of E include a fluorine atom, a chlorine 1 atom, a bromine atom, and an iodine atom.
  • Preferable examples of the "lower alkyl group" in the “lower alkyl group optionally substituted with one or more halogen atoms" which is a substituent of E include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, sec-pentyl, isopentyl, neopentyl, n- hexyl, isohexyl and the like, and
  • halogen atom the aforementioned "halogen atom" can be mentioned.
  • lower alkoxy group in the "lower alkoxy group optionally substituted with one or more halogen atoms" which is a substituent of E include methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, tert-butoxy, pentyloxy, tert-pentyloxy, 'neo-pentyloxy, hexyloxy,
  • halogen atom the aforementioned "halogen atom" can be mentioned.
  • Preferable examples of the "lower alkylsulfinyl group" in the “lower alkylsulfinyl group optionally substituted with one or more halogen atoms" which is a substituent of E include methylsulfinyl, ethylsulfinyl, n-propylsulfinyl, isopropylsulflnyl, n-butylsulfinyl, isobutylsulfinyl, sec- butylsulfinyl, tert-butylsulfinyl, n-pentylsulfinyl, sec- pentylsulfinyl, isopentylsulfinyl, neopentylsulfinyl, n- hexylsulfinyl, isohexylsulfinyl and the like, and
  • halogen atom the aforementioned "halogen atom" can be mentioned.
  • Preferable examples of the "lower alkylsulfonyl group" in the “lower alkylsulfonyl group optionally substituted with one or more halogen atoms" which is a substituent of E include methylsulfonyl, ethylsulfonyl, n-propylsulfonyl, isopropylsulfonyl, n-butylsulfonyl, isobutylsulfonyl, sec- butylsulfonyl, tert-butylsulfonyl, n-pentylsulfonyl, sec- pentylsulfonyl, isopentylsulfonyl, neopentylsulfonyl, n- hexylsulfonyl, isohexylsulfonyl and the like, and
  • halogen atom the aforementioned "halogen atom" can be mentioned.
  • aryl group represented by E include phenyl, 1-naphthyl, 2-naphthyl, biphenylyl, 2- anthryl and the like.
  • heterocyclic group represented by E include an "aromatic monocyclic
  • monocyclic heterocyclic group include 5-membered aromatic monocyclic heterocyclic groups such as 2-furyl, 3-furyl, 2- thienyl, 3-thienyl, 2-pyrrolyl, 3-pyrrolyl, 2-oxazolyl, A- oxazolyl, 5-oxazolyl, 3-isoxazolyl, 4-isoxazolyl, 5- isoxazolyl, 2-thiazolyl, 4-thiazolyl, 5-thiazolyl, 3- isothiazolyl, 4-isothiazolyl, 5-isothiazolyl, 2-imidazolyl, 4-imidazolyl, 5-imidazolyl, 3-pyrazolyl, 4-pyrazolyl, 5- pyrazolyl, 1, 2, 3-oxadiazol-4-yl, 1, 2, 3-oxadiazol-5-yl, 1, 2, 4-oxadiazol-5-yl, 1, 2, 4-oxadiazol-3-yl, 1,3,4- oxadiazol-2-yl, furazanyl,
  • 6-membered aromatic monocyclic heterocyclic groups such as 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyrimidinyl, A- pyrimidinyl, 5-pyrimidinyl, 3-pyridazinyl, 4-pyridazinyl, 2-pyrazinyl, 1, 2, 4-triazin-3-yl, 1, 2, 4-triazin-5-yl, 1,2,4- triazin-6-yl, 1, 3, 5-triazin-2-yl and the like.
  • substituted with one or more substituents include a halogen atom (fluorine atom, chlorine atom, bromine atom, iodine atom) , nitro, cyano, lower alkyl substituted with a halogen atom (e.g. chloromethyl, difluoromethyl,
  • heterocyclic group in the “heterocyclic group optionally substituted with one or more substituents” represented by Q include an "aromatic
  • aromatic monocyclic heterocyclic group include 5-membered aromatic monocyclic heterocyclic group such as 2-furyl, 3- furyl, 2-thienyl, 3-thienyl, 2-pyrrolyl, 3-pyrrolyl, 2- oxazolyl, 4-oxazolyl, 5-oxazolyl, 3-isoxazolyl, 4- isoxazolyl, 5-isoxazolyl, 2-thiazolyl, 4-thiazolyl, 5- thiazolyl, 3-isothiazolyl, 4-isothiazolyl, 5-isothiazolyl, 2-imidazolyl, 4-imidazolyl, 5-imidazolyl, 3-pyrazolyl, 4- pyrazolyl, 5-pyrazolyl, 1, 2, 3-oxadiazol J 4-yl, 1,2,3- oxadiazol-5-yl, 1, 2, 4-oxadiazol-5-yl, 1, 2, 4-oxadiazol-3-yl, 1, 3, 4-oxadiazol-2-yl, furazanyl, 1,
  • ⁇ -membered aromatic monocyclic heterocyclic groups such as 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyrimidinyl, 4- pyrimidinyl, 5-pyrimidinyl, 3-pyridazinyl, 4-pyridazinyl, 2-pyrazinyl, 1, 2, 4-triazin-3-yl, 1, 2, 4-triazin-5-yl, 1,2,4- triazin-6-yl, 1, 3, 5-triazin-2-yl and the like, and
  • substituents of the "one or more substituents" in the "heterocyclic group optionally substituted with one or more substituents” include a halogen atom (fluorine atom, chlorine atom, bromine atom, iodine atom) , nitro, cyano, lower alkyl optionally
  • halogen atom e.g. methyl, chlromethyl, difluoromethy, trichloromethyl, trifluoromethyl, ethyl, 2- bromoethyl, 2, 2, 2-trifluoroethyl, pentafluoroethyl, propyl, 3, 3, 3-trifluoropropyl, isopropyl, butyl, isobutyl, sec- butyl, tert-butyl, 4 , 4 , 4-trifluorobutyl, pentyl, isopentyl, neopentyl, 5, 5, 5-trifluoropentyl, hexyl, 6,6,6- trifluorohexyl etc.), lower alkoxy (e.g. methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, pentyloxy, hexyloxy etc.) and the like.
  • a halogen atom e.
  • Examples of aspects of the compound (I) include:
  • X and Y are an oxygen atom
  • R 1 is a hydrogen atom
  • R 2 is a methylene group, an ethylene group, or a trimethylene group
  • A is a group represented by OR 3
  • R 3 is a C1-C3 alkyl group optionally substituted with one or more substituents
  • R 4 is a C1-C3 alkyl group optionally substituted with one or more substituents
  • n is an integer of 0 to 2) , or
  • R 5 and R 6 each are independently a C1-C3 alkyl group optionally substituted with one or more substituents, or
  • R 5 and R 6 are taken together at the ends thereof to form together with the nitrogen atom a 3- to 7-membered nitrogen containing heterocycle optionally having another nitrogen atom, an oxygen atom and a sulfur atom as a ring constituting atom) ,
  • R 7 is a halogen atom
  • G is an oxygen atom or a sulfur atom
  • E is an aryl group or a heterocyclic group optionally substituted with one or more substituents selected from the group consisting of (1) a halogen atom, and (2) a lower alkyl group optionally substituted with one or more halogen atoms) ,
  • Q is a 2, 6-difluorophenyl group, a 2-chloro-6- fluorophenyl group, a 2, 6-dichlorophenyl group, a 3- chloropyridin-2-yl group, or a 3, 5-dichloropyridin-4-yl group, and
  • n is an integer of 1 to 4 (provided that when m is an integer of 2 to 4, R 7 S may be the same or different) .
  • X and Y are an oxygen atom
  • R 1 is a hydrogen atom
  • R 2 is a methylene group, an ethylene group, or a trimethylene group
  • N A is a group represented by OR 3
  • R 3 is a C1-C3 alkyl group optionally substituted with one or more substituents
  • R 4 is a C1-C3 alkyl group optionally substituted with one or more substituents
  • n is an integer of 0 to 2) , or
  • R 5 and R 6 each are independently a C1-C3 alkyl group optionally substituted with one or more substituents, or
  • R 5 and R 6 are taken together at the 'ends thereof to form together with the nitrogen atom a 3- to 7-membered nitrogen-containing heterocycle optionally having another nitrogen atom, an oxygen atom and a sulfur atom as a ring constituting atom) ,
  • R 7 is a halogen atom
  • a lower alkoxy lower alkylthio group optionally substituted with one, or more halogen atoms, or
  • G is " an oxygen atom or a sulfur atom
  • E is an aryl group or a heterocyclic group optionally substituted with one or more substituents selected from the group consisting of (1) a halogen atom, and (2) a lower alkyl group optionally substituted with one or more halogen atoms) ,
  • N ⁇ Q is a 2, 6-difluorophenyl group, a 2-chloro-6- fluorophenyl group, a 2 , 6-dichlorophenyl group, a 3- chloropyridin-2-yl group, or a 3, 5-dichloropyridin-4-yl group, and
  • n is an integer of 1 to 4 (provided that when m is an integer of 2 to 4, R 7 S may be the same or different) .
  • X and Y are an oxygen atom
  • R 1 is a hydrogen atom, methyl, 2-propenyl, 2-propynyl, benzyl, methoxymethyl, ethoxymethyl, 2-phenoxyethyl, methylthiomethyl, 2-methylthioethyl, 2-methylsulfinylethyl, 2-methylsulfonylethyl, 2-dimethylaminoethyl, or acetyl,
  • R 2 is a methylene group, an ethylene group, or a trimethylene group
  • A is a group represented by OR 3
  • R 3 is methyl, ethyl, 2-chloroethyl, acetyl, or benzyl
  • n is a integer of 0 to 2) , or
  • R 5 and R 6 are taken together at the ends thereof to form together with the nitrogen atom morpholino) ,
  • x ⁇ R 7 is a fluorine atom, a chlorine atom, tert- butoxycarbonyl, trifluoromethyl, 1, 1, 2, 2-tetrafluoroethoxy, trifluoromethoxy, 1,1, 2-trifluoro-2-trifluoromethoxyethoxy, trifluromethylthio, difluoromethylthio, methylthio,
  • Q is a 2, ⁇ -difluorophenyl group, a 2-chloro-6- N fluorophenyl group, a 2, 6-dichlorophenyl group, a 3- chloropyridin-2-yl group, or a 3, 5-dichloropyridin-4-yl group, and
  • n is an integer of 1 to 4 (provided that when m is an integer of 2 to 4, R 7 ' s may be the same or different) .
  • X and Y are an oxygen atom
  • R 1 is a hydrogen atom, methyl, 2-propenyl, 2-propynyl, benzyl, methoxymethyl, ethoxymethyl, 2-phenoxyethyl, methylthiomethyl, 2-methylthioethyl, 2-methylsulfonylethyl, or acetyl,
  • R 2 is a methylene group, an ethylene group, or a trimethylene group
  • A is a group represented by OR 3
  • R 3 is methyl, ethyl, 2-chloroethyl, acetyl, or benzyl
  • n is a integer of 0 to 2)
  • R 5 and R 6 are taken together at the ends thereof to form together with the nitrogen atom morpholino) ,
  • R is fluorine atom, a chlorine atom, tert- butoxycarbonyl, trifluoromethyl, 1, 1, 2, 2-tetrafluoroethoxy, trifluoromethoxy, 1, 1, 2-trifluoro-2-trifluoromethoxyethoxy, trifluromethylthio, difluoromethylthio, methylthio,
  • Q is a 2, 6-difluorophenyl group, a 2-chloro-6- fluorophenyl group, a 2, 6-dichlorophenyl group, a 3- chloropyridin-2-yl group, or a 3, 5-dichloropyridin-4-yl group, and
  • n is an integer of 1 to 4 (provided that when m is an integer of 2 to 4, R 7 ' s may be the same or different).
  • R 100 represents a halogen atom
  • R 200 represents a halogen atom
  • R 1-100 represents a hydrogen atom, a C1-C4 al kyl group or a
  • R 2"100 represents a C1-C4 al koxy group
  • R 7-100 ⁇ represents a hydrogen atom or halogen atom
  • R 7"200 represents a halogen atom, a C1-C4 alkoxy group optionally substituted with one or more halogen atoms, a C1-C4 alkylthio group optionally substituted with one or more halogen atoms, a C1-C4 alkylsulfinyl group optionally- substituted with one or more halogen atoms, or a C1-C4 alkylsulfonyl group optionally substituted with one or more halogen atoms.
  • R 100 is a fluorine atom or a chlorine atom
  • R 200 is a fluorine atom or a chlorine atom
  • R 1-100 is a hydrogen atom, a C1-C4 alkyl group or a C1-C4 alkoxy C1-C4 alkyl group
  • R 2"100 is a C1-C4 alkoxy group
  • R 7 - 2 ⁇ o ⁇ 3 a halogen atom, a C1-C4 alkoxy group optionally substituted with one or more halogen atoms, a C1-C4 alkylthio group optionally substituted with one or more halogen atoms, a C1-C4 alkylsulfinyl group optionally substituted with one or more halogen atoms / or a C1-C4 alkylsulfonyl group optionally substituted with one or more halogen atoms.
  • R 100 is a halogen atom
  • R 200 is a halogen atom
  • R 2"100 is a methoxy group
  • R 7"100 is a hydrogen atom, a fluorine atom or a chlorine atom
  • R 7"200 is a halogen atom, a C1-C4 alkoxy group optionally substituted with one or more halogen atoms, a C1-C4 alkylthio group optionally substituted with one or more halogen atoms, a C1-C4 alkylsulfinyl group optionally substituted with one or more halogen atoms, or a C1-C4 alkylsulfonyl group optionally substituted with one or more halogen atoms.
  • R 100 is a halogen atom
  • R 200 is a halogen atom
  • R i - i oo is a me thoxymethyl group
  • R 2"100 is a methoxy group
  • R7-ioo is a f]_ uor j_ ne atom
  • R 7"200 is a halogen atom, a C1-C4 alkoxy group optionally substituted with one or more halogen atoms, a C1-C4
  • alkylthio group optionally substituted with one or more halogen atoms
  • a C1-C4 alkylsulfinyl group optionally substituted with one or more halogen atoms
  • a C1-C4 alkylsulfonyl group optionally substituted with one or more halogen atoms.
  • R 100 is a fluorine atom, or a chlorine atom
  • R 200 is a fluorine atom or a chlorine atom
  • R i - i oo is a hydrO g en atom, a C1-C4 alkyl group or a C1-C4 alkoxy C1-C4 alkyl group,
  • R 2"100 is a C1-C4 alkoxy group
  • R 7"100 is a hydrogen atom, a fluorine atom or a chlorine atom
  • R 7 - 2 oo is a C1 _ C 4 alkylthio group optionally substituted with one or more halogen atoms.
  • R 100 is a fluorine atom or a chlorine atom
  • R 200 is a fluorine atom or a chlorine atom
  • R i - i oo is a hydrogen atom, a C1-C4 alkyl group or a C1-C4 alkoxy C1-C4 alkyl group,
  • R 2"100 is a C1-C4 alkoxy group
  • R 7"100 is a hydrogen atom, a fluorine atom or a chlorine atom
  • R 7 - 20O ⁇ 3 a trifluoromethylthio group.
  • R 100 is a fluorine atom or a chlorine atom
  • R 200 is a fluorine atom or a chlorine atom
  • R i - i oo is a hydrogen atom, a C1-C4 alkyl group or a C1-C4 alkoxy C1-C4 alkyl group>
  • R 2-ioo is a C1 _ C 4 alkoxy group
  • R 7 - 2 oo j ⁇ s a trifluoromethylthio group.
  • X 1 , Y 1 , R 1 , R 2"1 , R 7"1 and R 7"2 in the formula represent any of combinations described in “Table 1" to "Table 19".
  • Me a methyl group
  • the compound (I) can be produced, for example, by the following Process 1 to Process 10.
  • X is an oxygen atom
  • Y is an oxygen atom
  • R 11 is a Tower alkoxy lower alkyl group optionally substituted with one or more substituents, a lower
  • alkylthio lower alkyl group optionally substituted . with one or more substituents, a lower alkylsulfinyl lower alkyl group optionally substituted with one or more substituents, a lower alkylsulfonyl lower alkyl group optionally
  • R 7 , Q and m are as defined above, and
  • X is an oxygen atom
  • Y is an oxygen atom
  • R 11 is as defined above, and
  • L 1 is a halogen atom (chlorine atom, bromine atom, and iodine atom) , a methanesulfonyloxy group, a
  • the reaction is usually performed in a solvent in the presence of a base.
  • Examples of the solvent used in the reaction include ketones such as acetone, methyl ethyl ketone and the like, aromatic hydrocarbons such as benzene, toluene, xylene and the like, aliphatic hydrocarbons such as hexane, heptane and the like, ethers such as diethyl ether, tetrahydrofuran, 1,4-dioxane, 1, 2-dimethoxyethane, 1, 2-diethoxyethane and the like, halogenated hydrocarbons such as chloroform, chlorobenzene, dichlorobenzene and the like, nitriles such as acetonitrile and the like, aprotic polar solvents such as N, N-dimethylformamide, N, N-dimethylacetamide, 1-methyl- 2-pyrrolidone, 1, 3-dimethylimidazolinone, dimethyl
  • Examples of the base used in the reaction include hydroxides of an alkali metal or an alkaline earth metal such as sodium hydroxide, potassium hydroxide, calcium hydroxide and the like, hydrides of an alkali metal or an alkaline earth metal such as sodium hydride, potassium hydride, calcium hydride and the like, carbonates of an alkali metal or an alkaline earth metal such as sodium carbonate, potassium carbonate and the like, alcoholates of an alkali metal such as sodium ethylate, sodium methylate and the like, organic lithium such as normalbutyllithium, lithium diisopropylamide and the like, and organic bases such as triethylamine, pyridine, 1,8- diazabicyclo [5, 4, 0] undec-7-ene and the like.
  • Each reagent may be used in an excess amount in the reaction, when the reagent is liquid under reaction conditions. However, usually, the compound represented by the formula (III) is used at a proportion of 2 to 4 moles, and the base is used at a proportion of 2 to 4 moles based on 1 mole of the compound represented by the formula (II) .
  • the reaction temperature is usually in a range of -78 to 150°C, and the reaction time is usually in a range of 0.1 to 100 hours.
  • the compound represented by the formula (1-1) can be isolated by performing a post-treatment procedure such as by pouring the reaction mixture into water, extracting this with an organic solvent, and drying and concentrating the organic layer.
  • the isolated compound represented by the formula (1-1) can be further purified by recrystallization, column chromatography or the like.
  • the compound represented by the formula (II) can be produced by the process described in J. Agr. Food Chem. , Vol.21, No. 3, p.348-354 (1973), or modification thereof.
  • Process 2 Among the compounds (I) , a compound represented by the formula (1-2) :
  • R 2 , A, " R 7 ' Q and m are as defined above, and
  • X is an oxygen atom
  • Y is an oxygen atom
  • R 1"1 is a formyl group, a cyano group, ⁇

Abstract

The present invention relates to a benzoylurea compound represented by the formula (1): wherein R2 represents a lower alkylene group etc., and A represents a group represented by OR3, S(O) nR4 or NR5R6, or a salt thereof, and use of the same for controlling pests.

Description

DESCRIPTION BENZOYLUREA COMPOUND AND USE THEREOF Technical Field
The present invention relates to a benzoylurea
compound and use thereof for pest control.
Background Art
JP 61-15879 A and the like disclose benzoylurea compounds having a pest controlling activity.
Disclosure of the Invention
However, sometimes, these compounds do not necessarily exhibit a sufficient controlling efficacy for pests. An object of the present invention is to provide a compound having an excellent controlling efficacy for pests.
For achieving the aforementioned object, the present inventors have studied intensively and, as a result, found out that a benzoylurea compound represented by the
following formula (I) has an excellent controlling efficacy for pests. Thus, the present invention has been completed.
That is, the present invention relates to the
following [1] to [15] :
[I] A benzoylurea compound represented by the formula (I) :
Figure imgf000003_0001
wherein
X and Y each represent independently an oxygen atom or a sulfur atom,
R1 represents a hydrogen atom,
a formyl group,
a cyano group,
a lower alkylsulfonyl group optionally substituted with one or more substituents,
an arylsulfonyl group optionally substituted with one or more substituents,
a lower alkylcarbonylthio group optionally substituted with one or more substituents,
a lower alkoxycarbonylthio group optionally substituted with one or more substituents,
an aryloxycarbonylthio group optionally substituted with one or more substitutents,
a mono or di (lower alkyl) aminosulfonyl group optionally substituted with one or more substituents,
a mono or di (aryl) aminosulfonyl group optionally
substituted with one or more substitutents,
a lower alkyl group optionally substituted with one or more substituents, a lower alkenyl group optionally substituted with one or more substituents,
a lower alkynyl group optionally substituted with one or more substituents,
a lower cycloalkyl group optionally substituted with one or more substituents,
an aryl lower alkyl group optionally substituted with one or more substituents,
an aryl group optionally substituted with one or more substituents,
a lower alkoxy lower alkyl group optionally substituted withvone or more substituents,
an aryloxy lower alkyl group optionally substituted with one or more substituents,
a lower alkylthio lower alkyl group optionally substituted with one or more substituents,
a lower alkylsulfinyl lower alkyl group optionally
substituted with one ore more substituents,
a lower alkylsulfonyl lower alkyl group optionally
substituted with one or more substituents,
a mono or di (lower alkyl) amino lower alkyl group optionally substituted with one or more substituents,
a lower alkanoyl group optionally substituted with one or more substituents,
a lower alkoxycarbonyl group optionally substituted with one or more substituents,
an aryloxycarbonyl group optionally substituted with one or more substituents,
an aryl lower alkoxycarbonyl group optionally substituted with one or more substituents,
a carbamoyl group optionally substituted with one or more substituents,
a thiocarbamoyl group optionally substituted with one or more substituents,
a lower alkoxyoxalkyl group optionally substituted with one or more substituents,
an aryl lower alkoxyoxalyl group optionally substituted with one or more substituents,
an aryloxyoxalyl group optionally substituted with one or more substituents,
an aminooxalyl group optionally substituted with one or more substituents,
a lower alkoxy group optionally substituted with one or more substituents,
an aryloxy group optionally substituted with one or more substituents,
an aryl lower alkoxy group optionally substituted with one or more substituents,
an amino group optionally substituted with one or more substituents, or a heterocyclic group optionally substituted with one or more substituents,
R2 represents a lower alkylene group optionally substituted with one or more halogen atoms,
A represents:
(1) a group represented by OR3
(wherein R3 represents a C1-C3 alkyl group optionally substituted with one or more substituents,
a lower alkenyl group optionally substituted with one or more substituents,
a lower alkynyl group optionally substituted with one or more substituents,
a lower alkanoyl group optionally substituted with one or more substituents,
an aryl group optionally substituted with one or more substituents, or
an aryl lower alkyl group optionally substituted with one or more substituents),
(2) a group represented by S(O)nR4
(wherein R4 represents a C1-C3 alkyl group optionally substituted with one or more substituents,
a lower alkenyl group optionally substituted with one or more substituents,
a lower alkynyl group optionally substituted with one or more substituents, an aryl group optionally substituted with one or more substituents, or
an aryl lower alkyl group optionally substituted with one or more substituents, and
n represents an integer of 0, 1 or 2), or
(3) a group represented by NR5R6
(wherein R5 and R6 each represent independently
a C1-C3 alkyl group optionally substituted -with one or more substituents,
a lower alkenyl group optionally substituted with one or more substituents,
a lower alkynyl group optionally substituted with one or more substituents,
an aryl group optionally substituted with one or more substituents,
an aryl lower alkyl group optionally substituted with one or more substituents,
or R5 and R6 may be taken together at the ends thereof to form together with the nitrogen atom a 3- to 7-membered nitrogen-containing heterocyclic ring optionally having another nitrogen atom, an oxygen atom or a sulfur atom as a ring constituting atom) ,
R7 represents a halogen atom,
a nitro group,
a cyano group, an aryl lower alkoxy group optionally substituted with one or more halogen atoms,
a lower alkanoyl group optionally substituted with one or more halogen atoms,
a lower alkoxycarbonyl group optionally substituted with one or more halogen atoms,
an aryl group optionally substituted with one or more halogen atoms,
an aryl lower alkoxycarbonyl group optionally substituted with one or more halogen atoms,
an arylcarbamoyl group optionally substituted with one or more\halogen atoms,
a carbamoyl group optionally substituted with one or more lower alkyl groups,
a thiocarbamoyl group optionally substituted with one or more lower alkyl groups,
an amino group optionally substituted with one or more lower alkyl groups,
a lower alkyl group optionally substituted with one or more halogen atoms,
a lower alkoxy group optionally substituted with one or more halogen atoms,
a lower alkoxy lower alkoxy group optionally substituted with one or more halogen atoms,
a lower alkenyloxy group optionally substituted with one or more halogen atoms,
a lower alkynyloxy group optionally substituted with one or more halogen atoms,
a lower alkanoylamino group optionally substituted with one or more halogen atoms,
a lower alkylthio group optionally substituted with one or more halogen atoms,
a lower alkenylthio group optionally substituted with one or more halogen atoms,
a lower alkynylthio group optionally substituted with one or more halogen atoms,
a lower alkylsulfinyl group optionally substituted with one or more halogen atoms,
a lower alkenylsulfinyl group optionally substituted with one or more halogen atoms,
a lower alkynylsulfinyl group optionally substituted with one or more halogen atoms,
a lower alkylsulfonyl group optionally substituted with one or more halogen atoms,
a lower alkenylsulfonyl group optionally substituted with one or more halogen atoms,
a lower alkynylsulfonyl group optionally substituted with one or more halogen atoms,
a lower alkoxy lower alkylthio group optionally substituted with one or more halogen atoms, or a group represented by -G-E
(wherein G represents an oxygen atom, a1 sulfur atom, SO, or
SO2, and
E represents an aryl group or a heterocyclic group and said aryl group or said heterocyclic group may be
substituted with one or more substituents selected from the group consisting of (1) a halogen atom, (2) a lower alkyl group optionally substituted with one or more halogen atoms, (3) a lower alkoxy group optionally substituted with one or more halogen atoms, (4) a lower alkylthio group optionally substituted with one or more halogen atoms, (5) a lower alkylsulfinyl group optionally substituted with one or more halogen atoms, (6) a lower alkylsulfonyl group optionally substituted with one or more halogen atoms, (7) a cyano group, and (8) a nitro group),
Q represents an aryl group optionally substituted with one or more substituents, or a heterocyclic group
optionally substituted with one or more substituents, and m represents an integer of 1 to 5 (provided that when m is an integer of 2 to 5, R7 ' s may be the same or
different) (hereinafter, referred to as the compound (I)), or a salt thereof.
[2] The benzoylurea compound according to [1], wherein R7 is a halogen atom,
a lower alkoxycarbonyl group optionally substituted with one or more halogen atoms,
a lower alkyl group optionally substituted with one or more halogen atoms,
a lower alkoxy group optionally substituted with one or more halogen atoms,
a lower alkoxy lower alkoxy group optionally substituted with one or more halogen atoms,
a lower alkoxy lower alkylthio group optionally substituted with one or more halogen atoms,
a lower alkenyloxy group optionally substituted with one or more halogen atoms,
a lower alkynyloxy group optionally substituted with one or more halogen atoms,
a lower alkylthio group optionally substituted with one or more halogen atoms,
a lower alkenylthio group optionally substituted with one or more halogen atoms,
a lower alkynylthio group optionally substituted with one or more halogen atoms,
a lower alkylsulfinyl group optionally substituted with one or more halogen atoms,
a lower alkenylsulfinyl group optionally substituted with one or more halogen atoms,
a lower alkynylsulfinyl group optionally substituted with one or more halogen atoms, a lower alkylsulfonyl group optionally substituted with one or more halogen atoms,
a lower alkenylsulfonyl group optionally substituted with one or more halogen atoms,
a lower alkynylsulfonyl group optionally substituted with one of more halogen atoms, or
a group represented by -G-E
(wherein G is an oxygen atom, a sulfur atom, SO, or SO2, and
E is an aryl group or a heterocyclic group and said aryl group or said heterocyclic group may be substituted withx,one or more substituents, selected from the group consisting of (1) a halogen atom, (2) a lower alkyl group optionally substituted with one or more halogen atoms, (3) a lower alkoxy group optionally substituted with one or more halogen atoms, (4) a lower alkylthio group optionally substituted with one or more halogen atoms, (5) a lower alkylsulfinyl group optionally substituted with one or more halogen atoms, (6) a lower alkylsulfonyl group optionally substituted with one or more halogen atoms, (7) a cyano group, and (8) a nitro group) .
[3] The benzoylurea compound according to [1] or [2], wherein R1 is a hydrogen atom,
a lower alkyl group optionally substituted with one or more substituents, a lower alkenyl group optionally substituted with one or more substituents,
a lower alkynyl group optionally substituted with one or more substituents,
an aryl lower alkyl group optionally substituted with one or more substituents,
a lower alkoxy lower alkyl group optionally substituted with one or more substituents,
an aryloxy lower alkyl group optionally substituted with one or more substituents,
a lower alkanoyl group optionally substituted with one or more -substituents,
a lower alkylthio lower alkyl group optionally substituted with one or more substituents,
a lower alkylsulfinyl lower alkyl group optionally
substituted with one or more substituents,
a lower alkylsulfonyl lower alkyl group optionally
substituted with one or more substituents, or
a mono or di (lower alkyl) amino lower alkyl group optionally substituted with one or more substituents.
[4] The benzoylurea compound according to any one of [1] to
[3], wherein R2 is a C1-C4 alkylene group optionally substituted with one or more halogen atoms.
[5] The benzoylurea compound according to any one of [1] to [4], wherein X and Y are an oxygen atom, and A is a group represented by OR3
(wherein R3 is a C1-C3 alkyl group optionally substituted with one or more substituents,
a lower alkenyl group optionally substituted with one or more substituents,
a lower alkynyl group optionally substituted with one or more substituents,
a lower alkanoyl group optionally substituted with one or more substituents, or
an aryl lower alkyl group optionally substituted with one or more substituents).
[6] The benzoylurea compound according to any one of [1] to [5], wherein A is a group represented by OR3
(wherein R3 is a C1-C3 alkyl group optionally substituted with one or more substituents,
a lower alkanoyl group optionally substituted with one or more substituents, or
an aryl lower alkyl group optionally substituted with one or more substituents) .
[7] The benzoylurea compound according to any one of [1] to [4], wherein X and Y are an oxygen atom, and
A is a group represented by S(O)nR4
(wherein R4 is a C1-C3 alkyl group optionally substituted with one or more substituents,
a lower alkenyl group optionally substituted with one or more substituents,
a lower alkynyl group optionally substituted with one or more substituents, or
an aryl group optionally substituted with one or more substituents, and
ri is an integer of 0 to 2) .
[8] The benzoylurea compound according to any one of [1] to
[4], wherein X and Y are an oxygen atom, and
A is a group represented by NR5R6
(wherein R5 and R6 each are independently
a C1-C3 alkyl group optionally substituted with one or more substituents,
a lower alkenyl group optionally substituted with one or more substituents,
a lower alkynyl group optionally substituted with one or more substituents,
an aryl group optionally substituted with one or more substituents,
or R5 and R6 are taken together at the end thereof to form together with the nitrogen atom a 3- to 7-membered
nitrogen-containing heterocycle optionally having another nitrogen atom, an oxygen atom or a sulfur atom as a ring constituting atom) .
[9] The benzoylurea compound according to any one of [1] to [8], wherein Q is a phenyl group optionally substituted with one or more substituents selected from the group consisting of (1) a halogen atom, (2) a lower alkyl group optionally substituted with one or more halogen atoms, and (3) a lower alkoxy group optionally substituted with one or more halogen atoms, or
an aromatic monocyclic heterocyclic group optionally- substituted with one or more substituents selected from the group consisting of (1) a halogen atom, (2) a lower alkyl group optionally substituted with one or more halogen atoms, and (3) a lower alkoxy group optionally substituted with one or more halogen atoms.
[10] \The benzoylurea compound according to any one of [1] to [8], wherein Q is a phenyl group substituted with one or more halogen atoms, or an aromatic monocyclic heterocyclic group substituted with one or more halogen atoms.
[11] The benzoylurea compound according to [1], wherein X and Y are an oxygen atom,
R1 is a hydrogen atom,
a lower alkyl group optionally substituted with one or more substituents,
a lower alkenyl group optionally substituted with one or more substituents,
a lower alkynyl group optionally substituted with one or more substituents,
an aryl lower alkyl group optionally substituted with one or more substituents,
a lower alkoxy lower alkyl group optionally substituted with one or more substituents,
an aryloxy lower alkyl group optionally substituted with one or more substituents,
a lower alkylthio lower alkyl group optionally substituted with one or more substituents,
a lower alkylsulfinyl lower alkyl group optionally
substituted with one or more substituents,
a lower alkylsulfonyl lower alkyl group optionally
substituted with one or more substituents,
a mono or di (lower alkyl) amino lower alkyl group optionally substituted with one or more substituents, or
a lower alkanoyl group optionally substituted with one or more substituents,
R2 is a methylene group, an ethylene group, or a trimethylene group,
A is:
(1) a group represented by OR3
(wherein R3 is a C1-C3 alkyl group optionally substituted with one or more substituents,
a lower alkanoyl group optionally substituted with one or more substituents, or
an aryl lower alkyl group optionally substituted with one or more substituents) , (2) a group represented by S(O)nR4
(wherein R4 is a C1-C3 alkyl group optionally substituted with one or more substituents, and
n is an integer of 0 to 2), or
(3) a group represented by NR5R6
(wherein R5 and R6 each are independently a C1-C3 alkyl group optionally substituted with one or more substituents, or
R5 and R6 are taken together at the end thereof to form together with the nitrogen atom a 3- to 7-membered nitrogen-containing heterocycle optionally having another nitrogen atom, an oxygen atom or a sulfur atom as a ring constituting atom) ,
R7 is a halogen atom,
a lower alkoxycarbonyl group optionally substituted with one or more halogen atoms,
a lower alkyl group optionally substituted with one or more halogen atoms,
a lower alkoxy group optionally substituted with one or more halogen atoms,
a lower alkoxy lower alkoxy group optionally substituted with one or more halogen atoms,
a lower alkylthio group optionally substituted with one or more halogen atoms,
a lower alkenylthio group optionally substituted with one or more halogen atoms,
a lower alkynylthio group optionally substituted with one^ or more halogen atoms,
a lower alkylsulfinyl group optionally substituted with one or more halogen atoms,
a lower alkenylsulfinyl group optionally substituted with one or more halogen atoms,
a lower alkylsulfonyl group optionally substituted with one or more halogen atoms,
a lower alkenylsulfonyl group optionally substituted with one or more halogen atoms,
a lower alkoxy lower alkylthio group optionally substituted with one or more halogen atoms, or
a group represented by -G-E
(wherein G is an oxygen atom, or a sulfur atom, and
E is an aryl group or a heterocyclic group optionally substituted with one or more substituents selected from the group consisting of (1) a halogen atom, and (2) a lower alkyl group optionally substituted with one or more halogen atoms) ,
Q is a 2, β-difluorophenyl group, a 2-chloro-6- fluorophenyl group, a 2 , 6-dichlorophenyl group, a 3- chloropyridin-2-yl group, or a 3, 5-dichloropyridin-4-yl group, and
m is an integer of 1 to 4 (provided that when m is an integer of 2 to 4, R7 ' s may be the same or different) .
[12] The benzoylurea compound according ' to [1], wherein X and Y are an oxygen atom,
R1 is a hydrogen atom,
a lower alkyl group optionally substituted with one or more substituents, '
a lower alkenyl group optionally substituted with one or more substituents,
a lower alkynyl group optionally substituted with one or more substituents,
a lower alkoxy lower alkyl group optionally substituted with*one or more substituents,
an aryloxy lower alkyl group optionally substituted with one or more substituents,
a lower alkylthio lower alkyl group optionally substituted with one or more substituents,
a lower alkylsulfonyl lower alkyl group optionally
substituted with one or more substituents, or
a lower alkanoyl group optionally substituted with one or more substituents,
R2 is a methylene group, an ethylene group, or a trimethylene group,
A is:
(1) a group represented by OR3
(wherein R3 is a C1-C3 alkyl group optionally substituted with one or more substituents,
a lower alkanoyl group optionally substituted with one or more substituents, or
an aryl lower alkyl group optionally substituted with one or more substituents) ,
(2) a group represented by S(O)nR4
(wherein R4 is a C1-C3 alkyl group optionally substituted with one or more substituents, and
n is an integer of 0 to 2) , or
(3) a group represented by NR5R6
(wherein R5 and R6 each are independently a C1-C3 alkyl group optionally substituted with one or more substituents, or
R5 and R6 are taken together at the end thereof to form together with the nitrogen atom a 3- to 7-membered nitrogen-containing heterocycle optionally having another nitrogen atom, an oxygen atom or a sulfur atom as a ring constituting atom) ,
R7 is a halogen atom,
a lower alkoxycarbonyl group optionally substituted with one or more halogen atoms,
a lower alkyl group optionally substituted with one or more halogen atoms,
a lower alkoxy group optionally substituted with one or more halogen atoms, a lower alkoxy lower alkoxy group optionally substituted with one or more halogen atoms,
a lower alkylthio group optionally substituted with one or more halogen atoms,
a lower alkenylthio group optionally substituted with one or more halogen atoms,
a lower alkynylthio group optionally substituted with one or more halogen atoms,
a lower alkylsulfinyl group optionally substituted with one or more halogen atoms,
a lower alkenylsulfinyl group optionally substituted with one or more halogen atoms,
a lower alkylsulfonyl group optionally substituted with one or more halogen atoms,
a lower alkoxy lower alkylthio group optionally substituted with one or more halogen ' atoms, or
a group represented by -G-E
(wherein G is an oxygen atom, or a sulfur atom, and
E is an aryl group or a heterocyclic group and said aryl group or said heterocyclic group may be substituted with one or more substituents selected from the group consisting of (1) a halogen atom, and (2) a lower alkyl group optionally substituted with one or more halogen atoms) ,
Q is a 2, 6-difluorophenyl group, a 2-chloro-6- fluorophenyl group, a 2 , 6-dichloroρhenyl group, a 3- chloropyridin-2-yl group, or a 3, 5-dichloropyridin-4-yl group, and
m is an integer of 1 to 4 (provided that when m is an integer of 2 to 4, R7S may be the same or different) .
[13] A pest controlling agent comprising the benzoylurea compound as defined in any one of [1] to [12] or a salt thereof as an active ingredient.
[14] Use of the benzoylurea compound as defined in any one of [1] to [12] or a salt thereof for controlling pests.
[15] A method of controlling pests or plant-parasiting pests, which comprises applying an effective amount of the benzoylurea compound as defined in any one of [1] to [12] or a salt thereof to pests or habitats of pests.
Best Mode for Carrying Out the Invention
Hereinafter, preferable examples and specific examples of various definitions encompassed in the scope of the present invention used herein will be explained in detail.
The term "lower", unless otherwise indicated, means a group having 6 or less carbon atoms, preferably a group having 4 or less carbon atoms.
Preferably examples of "one or more" include 1 to 6, more preferably 1 to 4.
Preferable examples of the "lower alkyl group" and the "lower alkyl" include straight or branched C1-C6 alkyl groups such as methyl, ethyl, n-propyl, 'isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, sec-pentyl, isopentyl, neopentyl, n-hexyl, isohexyl and the like.
Preferable examples of the "C1-C3 alkyl group" and the "C1-C3 alkyl" - include straight or branched C1-C3 alkyl groups, specifically, methyl, ethyl, n-propyl, and
isopropyl.
Preferable examples of the "lower alkenyl group" include straight or branched C2-C6 alkenyl groups such as vinyl, allyl, isopropenyl, isobutenyl, 1-methylallyl, 2- pentenyl, and 2-hexenyl and the like.
Preferable examples of the "lower alkynyl group" include C2-C6 alkynyl groups such as ethynyl, 2-propynyl, 1-propynyl, 2-butynyl, 3-butynyl, 3-pentynyl, 3-hexynyl and the like.
Preferable examples of the "aryl group" and "aryl" include C6-C14 aromatic hydrocarbon groups such as a phenyl group optionally substituted with lower alkyl (e.g. phenyl, mesityl, xylyl, tolyl etc.), naphthyl, anthracenyl and the like, preferably phenyl and naphthyl, and this "aryl group" and "aryl" may have a suitable substituent such as lower alkyl group, halogen, aryl group and the like.
Examples of the "halogen" and the "halogen atom" include fluorine, chlorine, bromine and iodine. Preferable examples of the "lower alkoxy group" and the "lower alkoxy" include straight or branched C1-C6 alkoxy groups such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, tert-butoxy, pentyloxy, tert-pentyloxy, neopentyloxy, hexyloxy, isohexyloxy and the like, more preferably methoxy, ethoxy, propoxy, butoxy, pentyloxy, hexyloxy, and isohexyloxy.
Preferable examples of the "lower alkanoyl group" include straight or branched C1-C6 alkanoyl groups such as acetyl, 2-methylacetyl, 2, 2-dimethylacetyl, propionyl, butyryl, isobutyryl, pentanoyl, 2 , 2-dimethylpropionyl, hexanoyl and the like.
Preferable examples of the "lower cycloalkyl group" include cyclic C3-C6 alkyl groups such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and the like.
. Examples of the "heterocyclic group" include 5- to 14- membered, preferably 5- to 10-membered monocyclic to tricyclic, preferably monocyclic or dicyclic heterocyclic groups containing one or two kinds of 1 to 4, preferably 1 to 3 hetero atoms selected from a nitrogen atom, an oxygen atom and a sulfur atom in addition to carbon atoms as a ring constituting atom, specifically,
5-membered heterocyclic groups such as 2-thienyl, 3- thienyl, 2-furyl, 3-furyl, 2-pyrrolyl, 3-pyrrolyl, 2- pyrrolidinyl, 3-pyrrolidinyl, 2-oxazolyl, 4-oxazolyl, 5- oxazolyl, 3-isoxazolyl, 4-isoxazolyl, 5-isoxazolyl, 2- thiazolyl, 4-thiazolyl, 5-thiazolyl, 3-isothiazolyl, 4- isothiazolyl, 5-isothiazolyl, 3-pyrazolyl, 4-pyrazolyl, 5- pyrazolyl, 2-pyrazolidinyl, 3-pyrazolidinyl, 4- pyrazolidinyl, 2-imidazolyl, 4-imidazolyl, 5-imidazolyl, lH-l,2,3-triazol-4-yl, IH-I, 2, 3-triazol-5-yl, 1,2,4- triazol-3-yl, 1, 2 , 4-triazol-5-yl, lH-tetrazol-5-yl, 2H- tetrazol-5-yl and the like,
6-membered heterocyclic groups such as 2-pyridyl, 3- pyridyl, 4-pyridyl, N-oxide-2-pyridyl, N-oxide-3-pyridyl, N-oxide-4-pyridyl, 2-pyrimidinyl, 4-pyrimidinyl, 5- pyrifnidinyl, N-oxide-2-pyrimidinyl, N-oxide-4-pyrimidinyl, N-oxide-5-pyrimidinyl, 2-thiomorpholinyl, 3-thiomorpholinyl, 2-morpholinyl, 3-morpholinyl, 2-piperidyl, 3-piperidyl, 4- piperidyl, 2-thiopyranyl, 3-thiopyranyl, 4-thiopyranyl, 2- 4H-1, 4-oxazinyl, 3-4H-1, 4-oxazinyl, 2-4H-1, 4-thiazinyl, 3- 4H-1, 4-thiazinyl, 2-piperazinyl, 3-1, 2 , 4-triazinyl, 5- 1, 2, 4-triazinyl, 6-1, 2, 4-triazinyl, 2-1, 3, 5-triazinyl, 3- pyridazinyl, 4-pyridazinyl, 2-pyrazinyl, N-oxide-3- pyridazinyl, N-oxide-4-pyridazinyl and the like, and
dicyclic or tricyclic fused heterocyclic groups such as 1-indolyl, 3-indolyl, 4-indolyl, 5-indolyl, 6-indolyl, 7-indolyl, 2-benzofuryl, 3-benzofuryl, 4-benzofuryl, 5- benzofuryl, β-benzofuryl, 7-benzofuryl, 2-benzothiazolyl, 4-benzothiazolyl, 5-benzothiazolyl, β-benzothiazolyl, 7- benzothiazolyl, 2-benzoxazolyl, 4-benzoxazolyl, 5- benzoxazolyl, 6-benzoxazolyl, 7-benzoxazolyl, 2- benzimidazolyl, 4-benzimidazolyl, 5-benzimidazolyl, 6- benzimidazolyl, 7-benzimidazolyl, 2-quinolyl, 3-quinolyl, 4-quinolyl, 5-quinolyl, 6-quinolyl, 7-quinolyl, 8-quinolyl, 1-isoquinolyl, 3-isoquinolyl, 4-isoquinolyl, 5-isoquinolyl, β-isoquinolyl, 7-isoquinolyl, 3-isoquinolyl, 1-phthalazinyl, 4-phthalazinyl, 5-phthalazinyl, 6-phthalazinyl, 7- phthalazinyl, 2-quinazolinyl, 4-quinazolinyl, 5- quinazolinyl, β-quinazolinyl, 7-quinazolinyl, 8- quinazolinyl, 2-quinoxalinyl, 3-quinoxalinyl, 5- quinoxalinyl, 6-quinoxalinyl, 7-quinoxalinyl, 8- quinoxalinyl, 1-indolizinyl, 2-indolizinyl, 3-indolizinyl, 5-indolizinyl, 6-indolizinyl, 7-indolizinyl, 8-indolizinyl, 1-quinolizinyl, 2-quinolizinyl, 3-quinolizinyl, 4- quinolizinyl, 6-quinolizinyl, 7-quinolizinyl, 8- quinolizinyl, 9-quinolizinyl, 2-1, 8-naphthyridinyl, 3-1,8- naphthyridinyl, 4-1, 8-naphthyridinyl, 1-dibenzofuranyl, 2- dibenzofuranyl, 3-dibenzofuranyl, 4-dibenzofuranyl, 1- carbazolyl, 2-carbazolyl, 3-carbazolyl, 4-carbazolyl, 1- acridinyl, 2-acridinyl, 3-acridinyl, 4-acridinyl, 9- acridinyl, 1-phenanthridinyl, 2-phenanthridinyl, 3- phenanthridinyl, 4-phenanthridinyl, 5-phenanthridinyl, 6- phenanthridinyl, 7-phenanthridinyl, 8-phenanthridinyl, 9- phenanthridinyl, 1-chromanyl, 3-chroπιanyl, 4-chromanyl, 5- chromanyl, 6-chromanyl, 7-chromanyl, 8-chromanyl, 1- phenothiazinyl, 2-phenothiazinyl, 3-phenothiazinyl, A- phenothiazinyl, 6-phenothiazinyl, 7-phenothiazinyl, 8- phenothiazinyl, 9-phenothiazinyl, 1-phenoxazinyl, 2- phenoxazinyl, 3-phenoxazinyl, 4-phenoxazinyl, 6- phenoxazinyl, ~ 7-phenoxazinyl, 8-phenoxazinyl, 9- phenoxazinyl and the like.
As the "heterocyclic group", inter alia, a 5-, 6- or 7-membered (preferably 5- or 6-membered) heterocyclic group containing 1 to 3 hetero atoms selected from the group consisting of an oxygen atom, a sulfur atom and a nitrogen atom\in addition to carbon atoms is preferable.
Preferable examples of the "heterocyclic group" include 5- or 6-membered heterocyclic groups containing 1 to 3 hetero atoms selected from the group consisting of a nitrogen atom, an oxygen atom and a sulfur atom in addition to carbon atoms, specifically, such as 1-pyrrolidinyl, 2- pyrrolidinyl, 3-pyrrolidinyl, 2-imidazolinyl, 4- imidazolinyl, 2-pyrazolizinyl, 3-pyrazolizinyl, A- pyrazolizinyl, 1-piperidyl, 2-piperidyl, 3-piperidyl, A- piperidyl, 2-piperidyl, 3-piperidyl, 4-piperidyl, 1- piperazinyl, 2-piperazinyl, morpholinyl, 2-thienyl, 3- thienyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-furyl, 3-furyl, pyrazinyl, 2-pyrimidinyl, 3-pyrrolyl, 3-pyridazinyl, 3- isothiazolyl, and 3-isoxazolyl, particularly preferably 6- membered nitrogen-containing heterocyclic groups (e.g.
pyridyl etc.) and the like.
Other preferable examples of the "heterocyclic group" include an "aromatic heterocyclic group", for example, 5- to 14-membered, more preferably 5- to 10-membered
monocyclic to tricyclic, further more preferably monocyclic or dicyclic aromatic heterocyclic groups containing one kind or two kinds or 1 to 4, preferably 1 to 3 hetero atoms selected from a nitrogen atom, an oxygen atom and a sulfur atom in addition to carbon atoms as a ring constituting atom, specifically, 5-membered aromatic heterocyclic groups such- as 2-thienyl, 3-thienyl, 2-furyl, 3-furyl, 1-pyrrolyl, 2-pyrrolyl, 3-pyrrolyl, 2-oxazolyl, 4-oxazolyl, 5-oxazolyl, 3-isoxazolyl, 4-isoxazolyl, 5-isoxazolyl, 2-thiazolyl, 4- thiazolyl, 5-thiazolyl, 3-isothiazolyl, 4-isothiazolyl, 5- isothiazolyl, 3-pyrazolyl,• 4-pyrazolyl, 5-pyrazolyl, 2- imidazolyl, 4-imidazolyl, 5-imidazolyl, IH-I, 2, 3-triazol-4- yl, 1H-1,2, 3-triazol-5-yl, 1, 2 , 4-triazol-3-yl, 1,2,4- triazol-5-yl, 5-lH-tetrazol-5-yl, 5-2H-tetrazol-5-yl and the like,
6-membered aromatic heterocyclic groups such as 2- pyridyl, 3-pyridyl, 4-pyridyl, N-oxide-2-pyridyl, N-oxide- 3-pyridyl, N-oxide-4-pyridyl, 2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl, N-oxide-2-pyrimidinyl, N-oxide-4-pyrimidinyl, N-oxide-5-pyrimidinyl, 3-1, 2 , 4-triazinyl, 5-1, 2 , 4-triazinyl, 6-1,2, 4-triazinyl, 2-1, 3, 5-triazinyl, 3-pyridazinyl, A- pyridazinyl, 2-pyrazinyl, N-oxide-3-pyridazinyl, N-oxide-4- pyridazinyl and the like, and
dicyclic or tricyclic fused aromatic heterocyclic groups such as 2-benzofuryl, 3-benzofuryl, 4-benzofuryl, 5- benzofuryl, 6-benzofuryl, 7-benzofuryl, 2-benzothiazolyl, 4-benzothiazolyl, 5-benzothiazolyl, 6-benzothiazolyl, 7- benzothiazolyl, 2-benzoxazolyl, 4-benzoxazolyl, 5- benzoxazolyl, 6-benzoxazolyl, 7-benzoxazolyl, 1- benzimidazolyl, 2-benzimidazolyl, 4-benzimidazolyl, 5- benzimidazolyl, 6-benzimidazolyl, 7-benzimidazolyl, 2- quinolyl, 3-quinolyl, 4-quinolyl, 5-quinolyl, 6-quinolyl, 7-quinolyl, 8-quinolyl, 1-isoquinolyl, 3-isoquinolyl, A- isoquinolyl, 5-isoquinolyl, 6-isoquinolyl, 7-isoquinolyl, 8-isoquinolyl, 1-phthalazinyl, 4-phthalazinyl, 5- phthalazinyl, 6-phthalazinyl, 7-phthalazinyl, 2- quinazolinyl, 4-quinazolinyl, 5-quinazolinyl, 6- quinazolinyl, 7-quinazolinyl, 8-quinazolinyl, 2- quinoxalinyl, 3-quinoxalinyl, 5-quinoxalinyl, 6- quinoxalinyl, 7-quinoxalinyl, 8-quinoxalinyl, 1-indolizinyl, 2-indolizinyl, 3-indolizinyl, 5-indolizinyl, 6-indolizinyl, 7-indolizinyl, 8-indolizinyl, 2-1, 8-naphthyidinyl, 3-1,8- naphthyridinyl, 4-1, 8-naphthyridinyl, 1-dibenzofuranyl, 2- dibenzofuranyl, 3-dibenzofuranyl, 4-dibenzofuranyl, 1- carbazolyl, 2-carbazolyl, 3-carbazolyl, 4-carbazolyl, 1- acridinyl, 2-acridinyl, 3-acridinyl, 4-acridinyl, 9- acridinyl, 1-phenanthridinyl, 2-phenanthridinyl, 3- phenanthridinyl, 4-phenanthridinyl, 6-phenanthridinyl, 7- phenanthridinyl, 8-phenanthridinyl, 9-phenanthridinyl, 1- phenothiazinyl, 2-phenothiazinyl, 3-phenothiazinyl, 4- phenothiazinyl, 6-phenothiazinyl, 7-phenothiazinyl, 8- phenothiazinyl, 9-phenothiazinyl, 1-phenoxazinyl, 2- phenoxazinyl, 3-phenoxazinyl, 4-phenoxazinyl, 6- phenoxazinyl, 7-phenoxazinyl, 8-phenoxazinyl, 9- phenoxazinyl and the like.
Preferable examples of the "aromatic heterocyclic group" include 5- or 6-membered heterocyclic groups
containing 1 to 3 hetero atoms selected from the group consisting of a nitrogen atom, an oxygen atom, and a sulfur atom in addition to carbon atoms, specifically, such as 2- thienyl, 3-thienyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2- furyl, 3-furyl, pyrazinyl, 2-pyrimidinyl, 3-pyrrolyl, 3- pyridazinyl, 3-isothiazolyl, and 3-isoxazolyl, particularly preferably, 6-membered nitrogen-containing aromatic
heterocyclic groups (e.g. pyridyl etc.) and the like.
Further preferable examples of the "heterocyclic group" include an "aromatic monocyclic heterocyclic group", for example, 5-membered aromatic monocyclic heterocyclic groups such as 2-furyl, 3-furyl, 2-thienyl, 3-thienyl, 2- pyrrolyl, 3-pyrrolyl, 2-oxazolyl, 4-oxazolyl, 5-oxazolyl, 3-isoxazolyl, 4-isoxazolyl, 5-isoxazolyl, 2-thiazolyl, 4- thiazolyl, 5-thiazolyl, 3-isothiazolyl, '4-isothiazolyl, 5- isothiazolyl, 2-imidazolyl, 4-imidazolyl, 5-imidazolyl, 3- pyrazolyl, 4-pyrazolyl, 5-pyrazolyl, 1, 2 , 3-oxadiazol-4-yl, 1, 2, 3-oxadiazol-5-yl, 1, 2, 4-oxadiazol-5-yl, 1,2,4- oxadia'zol-3-yl, 1, 3, 4-oxadiazol-2-yl, furazanyl, 1,2,3- thiadiazol-4-yl, 1, 2, 3-thiadiazol-5-yl, 1, 2, 4-thiadiazol-3- yl, 1,2, 4-thiadiazol-5-yl, 1, 3, 4-thiadiazol-2-yl, IH-I, 2,3- triazol-4-yl, IH-I, 2 , 3-triazol-5-yl, IH-I, 2, 4-triazol-3-yl, lH-tetrazol-5-yl and the like, and
β-membered aromatic monocyclic heterocyclic groups suchNas 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyrimidinyl, A- pyrimidinyl, 5-pyrimidinyl, 3-pyridazinyl, 4-pyridazinyl, 2-pyrazinyl, 1, 2, 4-triazin-3-yl, 1, 2, 4-triazin-5-yl, 1,2,4- triazin-β-yl, 1, 3, 5-triazin-2-yl and the like.
Preferable examples of the "lower alkylsulfonyl group" in the "lower alkylsulfonyl group optionally substituted with one or more substituents" represented by R1 include methylsulfonyl, ethylsulfonyl, n-propylsulfonyl,
isopropylsulfonyl, n-butylsulfonyl, isobutylsulfonyl, sec- butylsulfonyl, tert-butylsulfonyl, n-pentylsulfonyl, sec- pentylsulfonyl, isopentylsulfonyl, neopentylsulfonyl, n- hexylsulfonyl, isohexylsulfonyl and the like.
Preferable examples of the "substituent" of the "one or more substituents" in the "lower alkylsulfonyl group optionally substituted with one or more substituents" include a halogen atom (fluorine atom, chlorine atom, bromine atom, iodine atom), nitro, cyano, hydroxyl, lower cycloalkyl optionally substituted with a halogen atom (e.g. cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl etc.), lower alkoxy (e.g. methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, pentyloxy, hexyloxy etc.), amino, mono- or di- (lower alkyl) amino (e.g. methylamino, ethylamino, dimethylamino, diethylamino etc.), carboxyl, lower alkanoyl (e.g. acetyl, propionyl etc.), lower alkoxycarbonyl (e.g. methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl,
butoxycarbonyl etc.), carbamoyl, thiocarbamoyl, mono- or di- (lower alkyl) carbamoyl (e.g. methylcarbamoyl,
ethylcarbamoyl, dimethylcarbamoyl, diethylcarbamoyl etc.), arylcarbamoyl (e.g. phenylcarbamoyl, naphthylcarbamoyl etc.), aryloxy (e.g. phenyloxy, naphthyloxy etc.), lower alkylcarbonylamino optionally substituted with a halogen atom (e.g. acetylamino, trifluoroacetylamino etc.), lower alkylthio (e.g. methylthio etc.), lower alkylsulfinyl (e.g. methylsulfinyl etc.), lower alkylsulfonyl (e.g.
methylsulfonyl etc.), arylsulfinyl (e.g. phenylsulfinyl, naphthylsulfinyl etc.), arylsulfonyl (e.g. phenylsulfonyl, naphthylsulfonyl etc.) and the like.
Preferable examples of the "arylsulfonyl group" in the "arylsulfonyl group optionally substituted with one or more substituents" represented by R1 include phenylsulfonyl, naphthylsulfonyl and the like.
Preferable examples of the "substituent" of the "one or more substituents" in the "arylsulfonyl group optionally substituted with one or more substituents" include a
halogen atom (fluorine atom, chlorine atom, bromine atom, iodine atom) , nitro, cyano, hydroxyl, lower alkyl
substituted with a halogen atom (e.g. chloromethyl,
difluoromethyl, trichloromethyl, trifluoromethyl, 2- bromoethyl, 2 , 2, 2-trifluoroethyl, pentafluoroethyl, 3,3,3- trifluoropropyl, 4 , 4 , 4-trifluorobutyl, 5,5,5- trifluoropentyl, 6, 6, β-trifluorohexyl etc.), lower
cycloalkyl optionally substituted with a halogen atom (e.g. cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl etc.), lower alkoxy (e.g. methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, pentyloxy, hexyloxy etc.), amino, mono- or di- (lower alkyl) amino (e.g. methylamino, ethylamino, dimethylamino, diethylamino etc.), carboxyl, lower alkanoyl (e.g. acetyl, propionyl etc.), lower alkoxycarbonyl (e.g. methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl,
butoxycarbony etc.), carbamoyl, thiocarbamoyl, mono- or di- (lower alkyl) carbamoyl (e.g. methylcarbamoyl, ethylcarbamyl, dimethylcarbamoyl, diethylcarbamoyl etc.), arylcarbamoyl (e.g. phenylcarbamoyl, naphthylcarbamoyl etc.), aryloxy (e.g. phenyloxy, naphthyloxy etc.), lower alkylcarbonylamino optionally substituted with a halogen atom (e.g. acetylamino, trifluoroacetylamino etc.), lower alkylthio (e.g. methylthio etc.), lower alkylsulfinyl (e.g. methylsulfinyl etc.), lower alkylsulfonyl (e.g.
methylsulfonyl etc.), arylsulfinyl (e.g. phenylsulfinyl, naphthylsulfinyl etc.), arylsulfonyl (e.g. phenylsulfonyl, naphthylsulfonyl etc.) and the like.
Preferable examples of the "lower alkylcarbonylthio group" in the "lower alkylcarbonylthio group optionally substituted with one or more substituents" represented by R1 include methylcarbonylthio, ethylcarbonylthio, n- propylcarbonylthio, isopropylcarbonylthio, n- butylcarbonylthio, isobutylcarbonylthio, sec- butylcarbonylthio, tert-butylcarbonylthio, n- pentylcarbonylthio, sec-pentylcarbonylthio,
isopentylcarbonylthio, neopentylcarbonylthio, n- hexylcarbonylthio, isohexylcarbonylthio and the like.
Preferable examples of the "substituent" of the "one or more substituents" in the "lower alkylcarbonylthio group optionally substituted with one or more substituents" include the same substituent as the "substituent"
exemplified for the "lower alkylsulfonyl group optionally substituted with one or more substituents".
Preferable examples of the "lower alkoxycarbonylthio group" in the "lower alkoxycarbonylthio group optionally substituted with one or more substituents" represented by R1 include methoxycarbonylthio, ethoxycarbonylthio,
propoxycarbonylthio, isopropoxycarbonylthio,
butoxycarbonylthio, isobutoxycarbonylthio, tert- butoxycarbonylthio, pentyloxycarbonylthio, tert- pentyloxycarbonylthio, neo-pentyloxycarbonylthio,
hexyloxycarbonylthio, isohexyloxycarbonylthio and the like, and
preferable examples of the "substituent" of the "one or more substituents" in the "lower alkoxycarbonylthio group optionally substituted with one or more substituents" include the same substituent as the "substituent"
exemplified for the "lower alkylsulfonyl group optionally substituted with one or more substituents".
Preferable examples of the "aryloxycarbonylthio group" in the "aryloxycarbonylthio group optionally substituted with one or more substituents" represented by R1 include phenyloxycarbonylthio, naphthyloxycarbonylthio group, and preferable examples of the "substituent" of the "one or more substitutents" in the "aryloxycarbonylthio group optionally substituted with one or more substituents" include the same substituent as the "substituent"
exemplified for the "arylsulfonyl group optionally
substituted with one or more substituents".
Preferable examples of the "mono or di (lower alkyl) aminosulfonyl group" in the "mono or di (lower
alkyl) aminosulfonyl group optionally sub'stituted with one or more substituents" represented by R1 include
methylaminosulfonyl, dimethylaminosuIfonyl,
ethylmethylaminosulfonyl, diethylaminosulfonyl and the like, and
preferable examples of the "substitutent" of the "one or more substituents" in the "mono or di (lower
alkyl) aminosulfonyl group optionally substituted with one or more substituents" include the same substituent as the "substituent" exemplified for the "lower alklysulfonyl group optionally substituted with one or more substituents".
Preferable examples of the "mono or
di (aryl) aminosulfonyl group" in the "mono or
di (aryl) aminosulfonyl group optionally substituted with one or more substituents" represented by R1 include
phenylaminosulfonyl, diphenylaminosulfonyl,
naphthylaminosulfonyl and the like, and
preferable examples of the "substitutent" of the "one or more substituents" in the "mono or di (aryl) aminosulfonyl group optionally substituted with one or more substituents" include the same substituent as the "substituent"
exemplified for the "arylsulfonyl group optionally
substituted with one or more substituents".
Preferable examples of the "lower alkyl group" in the "lower alkyl group optionally substituted with one or more substituents" represented by R1 include methyl, ethyl, n- propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, sec-pentyl, isopentyl, neopentyl, n-hexyl,
isohexyl and the like, and
preferable examples of the "substituent" of the "one or more substituents" in the "lower alkyl group optionally substituted with one or more substituents" include a
halogen atom (fluorine atom, chlorine atom, bromine atom, iodine atom), nitro, cyano, lower alkanoyl (e.g. acetyl, propionyl etc.), lower alkoxycarbonyl (e.g. methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, butoxycarbonyl etc.), lower cycloalkyl optionally substituted with a halogen atom (e.g. cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl etc.), a heterocyclic group, and the like, and
herein, preferable examples of the "heterocyclic group" include an "aromatic monocyclic heterocyclic group", and examples of the aromatic monocyclic heterocyclic group include 5-membered aromatic monocyclic heterocyclic groups such as 2-furyl, 3-furyl, 2-thienyl, 3-thienyl, 3-pyrrolyl, 3-pyrrolyl, 2-oxazolyl, 4-oxazolyl, 5-oxazolyl, 3- lsoxazolyl, 4-isoxazolyl, 5-isoxazolyl, 2-thiazolyl, 4- thiazolyl, 5-thiazolyl, 3-isothiazolyl, 4-isothiazolyl, 5- lsothiazolyl, 2-imidazolyl, 4-imidazolyl, 5-imidazolyl, 3- pyrazolyl, 4-pyrazolyl, 5-pyrazolyl, 1, 2, 3-oxadiazol-4-yl, 1,2, 3-oxadiazol-5-yl, 1, 2, 4-oxadiazol-5-yl, 1,2,4- oxadiazol-3-yl, 1, 3, 4-oxadiazol-2-yl, furazanyl, 1,2,3- thiadiazol-4-yl, 1, 2, 3-thiadiazolyl-5-yl, 1, 2, 4-thiadiazol- 3-yl, 1,2, 4-thiadiazol-5-yl, 1, 3, 4-thiadiazol-2-yl, IH- 1,2, 3-triazol-4-yl, IH-I, 2, 3-triazol-5-yl, IH-I, 2,4- triazol-3-yl, -lH-tetrazol-5-yl and the like, and
6-membered aromatic monocyclic heterocyclic groups such as 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyrimidinyl, 4- pyrimidinyl, 5-pyrimidinyl, 3-pyridazinyl, 4-pyridazinyl, 2-pyrazinyl, 1, 2, 4-triazin-3-yl, 1, 2, 4-triazin-5-yl, 1,2,4- triazin-β-yl, 1, 3, 5-triazin-2-yl and the like.
'■-Preferable examples of the "lower alkenyl group" in the "lower alkenyl optionally substituted with one or more substituents" represented by R1 include vinyl, allyl, isopropentyl, isobutenyl, 1-methylallyl, 2-pentenyl, 2- hexenyl and the like, and
preferable examples of the "substituent" of the "one or more substitutents" in the "lower alkenyl optionally substituted with one or more substituents" include a halogen atom (fluorine atom, chlorine atom, bromine atom, iodine atom) , nitro, cyano, hydroxyl, lower cycloalkyl optionally substituted with a halogen atom (e.g.
cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl etc.), lower alkoxy (e.g. methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, pentyloxy, hexyloxy etc.), amino, mono- or di- (lower alkyl) ammo (e.g. methylamino, ethylamino, dimethylamino, diethylamino etc.), carbo'xyl, lower
alkyanoyl (e.g. acetyl, propionyl etc.), lower
alkoxycarbonyl (e.g. methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, butoxycarbonyl etc.), carbamoyl,
thiocarbamoyl, mono-or di- (lower alkyl) carbamoyl (e.g.
methylcarbamoyl, ethylcarbamoyl, dimethylcarbamoyl,
diethylcarbamoyl etc.), arylcarbamoyl (e.g: phenylcarbamoyl, naphthylcarbamoyl etc.), aryl (e.g. phenyl, naphthyl etc.), aryloxy (e.g. phenyloxy, naphthyloxy etc.), lower
alkylcarbonylamino optionally substituted with a halogen atorrΛ (e . g. acetylamino, trifluoroacetylamino etc.), lower alkylthio (e.g. methylthio etc.), lower alkylsulfinyl (e.g. methylsulfinyl etc.), lower alkylsulfonyl (e.g.
methylsulfonyl etc.), arylthio (e.g. phenylthio,
naphthylthio etc.), arylsulfinyl (e.g. phenylsulfinyl, naphthylsulfinyl etc.), arylsulfonyl (e.g. phenylsulfonyl, naphthylsulfonyl etc.) and the like.
Preferable examples of the "lower alkynyl group" in the "lower alkynyl group optionally substituted with one or more substituents" represented by R1 include ethynyl, 2- propynyl, 1-propynyl, 2-butynyl, 3-butynyl, 3-pentynyl, 3- hexynyl and the like, and
preferable examples of the "substituent" of the "one or more substitutents" in the "lower alkynyl group optionally substituted with one or more substituents" include a halogen atom (fluorine atom, chlorine atom, bromine atom, iodine atom) , nitro, cyano, hydroxyl, lower cycloalkyl optionally substituted with a halogen atom (e.g. cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl etc.), lower alkoxy (e.g. methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, pentyloxy, hexyloxy etc.), amino, mono- or di- (lower alkyl) amino (e.g. methylamino; ethylamino, dimethylamino, diethylamino etc.), carboxyl, lower alkanoyl (e.g. acetyl, propionyl etc.), lower alkoxycarbonyl (e.g. methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl,
butoxycarbonyl etc.), carbamoyl, thiocarbamoyl, mono-or di- (lower alkyl) carbamoyl (e.g. methylcarbamoyl,
ethylcarbamoyl, dimethylcarbamoyl, diethylcarbamoyl etc.), arylcarbamoyl (e.g. phenylcarbamoyl, naphthylcarbamoyl etc.), aryl (e.g. phenyl, naphthyl etc.), aryloxy (e.g. phenyloxy, naphthyloxy etc.), lower alkylcarbonylamino optionally substituted with a halogen atom (e.g.
acetylamino, trifluoroacetylamino etc.), lower alkylthio (e.g. methylthio etc.), lower alkylsulfinyl (e.g.
methylsulfinyl etc.), lower alkylsulfonyl (e.g.
methylsulfonyl etc.), arylthio (e.g. phenylthio,
naphthylthio etc.), arylsulfinyl (e.g. phenylsulfinyl, naphthylsulfinyl etc.), arylsulfonyl (e.g. phenylsulfonyl, naphthylsulfonyl etc.) and the like. Preferable examples of the "lower cycloalkyl group" in the "lower cycloalkyl group optionally substituted with one or more substituents" represented by R1 include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and the like, and
preferable examples of the "substituent" of the "one or more substitutents" in the "lower cycloalkyl group optionally substituted with one or more substituents" include a halogen atom (fluorine atom, chlorine atom, bromine atom, iodine atom) , nitro, cyano, hydroxyl, lower alkyl optionally substituted with a halogen atom (e.g.
methyl, chloromethyl, difluoromethyl, trichloromethyl, trifluoromethyl, ethyl, 2-bromoethyl, 2, 2, 2-trifluoroethyl, pentafluoroethyl, propyl, 3, 3, 3-trifluoropropyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, 4,4,4- trifluorobutyl, pentyl, isopentyl, neopentyl, 5,5,5- trifluoropentyl, hexyl, 6, 6, 6-trifluorohexyl etc.), lower alkoxy (e.g. methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, pentyloxy, hexyloxy etc.), amino, mono- or di- (lower alkyl) amino (e.g. methylamino, ethylamino,
dimethylamino, diethylamino etc.), carboxyl, lower alkanoyl (e.g. acetyl, propionyl etc.), lower alkoxycarbonyl (e.g. methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl,
butoxycarbonyl etc.), carbamoyl, thiocarbamoyl, mono- or di- (lower alkyl) carbamoyl (e.g. methylcarbamoyl,
ethylcarbamoyl, dimethylcarbamoyl, diethylcarbamoyl etc.), arylcarbamoyl (e.g. phenylcarbamoyl, naphthylcarbamoyl etc.), aryl (e.g. phenyl, naphthyl etc.)1, aryloxy (e.g. phenyloxy, naphthyloxy etc.), lower alkylcarbonylamino optionally substituted with a halogen atom (e.g.
acetylamino, trifluoroacetylamino etc.), lower alkylthio (e.g. methylthio etc.), lower alkylsulfinyl (e.g.
methylsulfinyl etc.), lower alkylsulfonyl (e.g.
methylsulfonyl etc.), arylthio (e.g. phenylthio,
naphthylthio etc.), arylsulfinyl (e.g. phenylsulfinyl, naphthylsulfinyl etc.), arylsulfonyl (e.g. phenylsulfonyl, naphthylsulfonyl etc.) and the like.
.Preferable examples of the "aryl lower alkyl group" in the "aryl lower alkyl group optionally substituted with one or more substituents" represented by R1 include benzyl, naphthylmethyl, anthracenylmethyl group and the like, and preferable examples of the "substituent" of the "one or more substitutents" in the "aryl lower alkyl group optionally substituted with one or more substituents" include a halogen atom (fluorine atom, chlorine atom, bromine atom, iodine atom), nitro, cyano, hydroxyl, lower alkyl substituted with a halogen atom (e.g. chloromethyl, difluoromethyl, trichloromethyl, trifluoromethyl, 2- bromoethyl, 2, 2, 2-trifluoroethyl, pentafluoroethyl, 3,3,3- trifluoropropyl, 4 , 4 , 4-trifluorobutyl, 5,5,5- trifluoropentyl, 6, 6, 6-trifluorohexyl etc.), lower cycloalkyl optionally substituted with a halogen atom (e.g. cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl etc.), lower alkoxy (e.g. methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, pentyloxy, hexyloxy etc.), amino, mono- or di- (lower alkyl) amino (e.g. methylamino, ethylamino, dimethylamino", diethylamino etc.), carboxyl, lower alkanoyl (e.g. acetyl, propionyl etc.), lower alkoxycarbonyl (e.g. methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl,
butoxycarbonyl etc. ) , carbamoyl, thiocarbamoyl, mono- or di- (lower alkyl) carbamoyl (e.g. methylcarbamoyl,
ethylcarbamoyl, dimethylcarbamoyl, diethylcarbamoyl etc.), arylearbamoyl (e.g. phenylcarbamoyl, naphthylcarbamoyl etc.), aryloxy (e.g. phenyloxy, naphthyloxy etc.), lower alkylcarbonylamino optionally substituted with a halogen atom (e.g. acetylamino, trifluoroacetylamino etc.), lower alkylthio (e.g. methylthio etc.), lower alkylsulfinyl (e.g. methylsulfinyl etc.), lower alkylsulfonyl (e.g.
methylsulfonyl etc.), arylthio (e.g. phenylthio,
naphthylthio etc.), arylsulfinyl (e.g. phenylsulfinyl, naphthylsulfinyl etc.), arylsulfonyl (e.g. phenylsulfonyl, naphthylsulfonyl etc.) and the like.
Preferable examples of the "aryl group" in the "aryl group optionally substituted with one or more substituents" represented by R1 include phenyl, mesityl, xylyl, tolyl, naphthyl, anthracenyl, indanyl, biphenyl and the like, and preferable examples of the "substituent" of the "one or more substitutents" in the "aryl group optionally substituted with one or more substituents" include a halogen atom (fluorine atom, chlorine atom, bromine atom, iodine atom) , nitro, cyano, hydroxyl, lower alkyl
substituted with a halogen atom (e.g. chloromethyl,
difluoromethyl, trichloromethyl, trifluoromethyl, 2- bromoethyl, 2, 2, 2-trifluoroethyl, pentafluoroethyl, 3,3,3- trifluoropropyl, 4, 4 , 4-trifluorobutyl, 5,5,5- trifluoropentyl, 6, 6, β-trifluorohexyl etc.), lower
cycloalkyl optionally substituted with a halogen atom (e.g. cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl etc.), lower alkoxy (e.g. methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, pentyloxy, hexyloxy etc.), amino, mono- or di- (lower alkyl) amino (e.g. methylamino, ethylamino, dimethylamino, diethylamino etc.), carboxyl, lower alkanoyl (e.g. acetyl, propionyl etc.), lower alkoxycarbonyl (e.g. methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl,
butoxycarbonyl etc.), carbamoyl, thiocarbamoyl, mono- or di- (lower alkyl) carbamoyl (e.g. methylcarbamoyl,
ethylcarbamoyl, dimethylcarbamoyl, diethylcarbamoyl etc.), arylcarbamoyl (e.g. phenylcarbamoyl, naphthylcarbamoyl etc.), aryloxy (e.g. phenyloxy, naphthyloxy etc.), lower alkylcarbonylamino optionally substituted with a halogen atom (e.g. acetylamino, trifluoroacetylamino etc.), lower alkylthio (e.g. methylthio etc.), lower alkylsulfinyl (e.g. methylsulfinyl etc.), lower alkylsulfonyl (e.g.
methylsulfonyl etc.), arylthio (e.g. phenylthio,
naphthylthio etc.), arylsulfinyl (e.g. phenylsulfinyl, naphthylsulfinyl etc.), arylsulfonyl (e.g. phenylsulfonyl, naphth'ylsulfonyl etc.) and the like.
Preferable example of the "lower alkoxy lower alkyl group" in the "lower alkoxy lower alkyl group optionally substituted with one or more substituents" represented by R1 include methoxymethyl, ethoxymethyl, 2-methoxyethyl, 2- ethoxyethyl, 3-methoxypropyl, 3-ethoxypropyl, 4- methoxybutyl, 4-ethoxybutyl, 5-methoxypentyl, 5- ethoxypentyl, β-methoxyhexyl, 6-ethoxyhexyl and the like, and
preferable examples of the "substituent" of the "one or more substituents" in the "lower alkoxy lower alkyl group optionally substituted with one or more substituents" include a halogen atom (fluorine atom, chlorine atom, bromine atom, iodine atom) , nitro, cyano, lower cycloalkyl optionally substituted with a halogen atom (e.g.
cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl etc.), lower alkoxy (e.g. methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, pentyloxy, hexyloxy etc.), amino, mono- or di- (lower alkyl) amino (e.g. methylamino, ethylamino, dimethylamino, diethylamino etc.), carboxyl, lower alkanoyl (e.g. acetyl, propionyl etc.), lower alkoxycarbonyl (e.g. methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl,
butoxycarbonyl etc.), carbamoyl, thiocarbamoyl, mono- or di- (lower alkyl) carbamoyl (e.g. methylcarbamoyl,
ethylcarbamoyl, dimethylcarbamoyl, diethylcarbamoyl etc.), arylcarbamoyl " (e . g . phenylcarbamoyl, naphthylcarbamoyl etc.), aryl (e.g. phenyl, napthyl etc.), aryloxy (e.g.
phenyloxy, naphthyloxy etc.), lower alkylcarbonylamino optionally substituted with a halogen atom (e.g.
acetylamino, trifluoroacetylamino etc.), lower alkylthio (e.g. methylthio etc.), lower alkylsulfinyl (e.g.
methylsulfinyl etc.), lower alkylsulfonyl (e.g.
methylsulfonyl etc.), arylthio (e.g. phenylthio,
naphthylthio etc.), arylsulfinyl (e.g. phenylsulfinyl, naphthylsulfinyl etc.), arylsulfonyl (e.g. phenylsulfonyl, naphthylsulfonyl etc.) and the like.
Preferable examples of the "aryloxy lower alkyl group" in the "aryloxy lower alkyl group optionally substituted with one or more substituents" represented by R1 include phenoxymethyl, 2-phenoxyethyl, 3-phenoxypropyl and the like, and
preferable examples of the "substituent" of the "one or more substituents" in the "aryloxy lower alkyl group optionally substituted with one or more substituents" include a halogen atom (fluorine atom, chlorine atom, bromine atom, iodine atom) , nitro, cyano, hydroxyl, lower cycloalkyl optionally substituted with a halogen atom (e.g. cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl etc.), lower alkyl substituted with a halogen atom (e.g.
chloromethyl, difluoromethyl, trichloromethyl,
trifluoromethyl, 2-bromoethyl, 2, 2, 2-trifluoroethyl,
pentafluoroethyl, 3, 3, 3-trifluoropropyl, 4,4,4- trifluorobutyl, 5, 5, 5-trifluoropentyl, 6, 6, β-trifluorohexyl etc.), lower alkoxy (e.g. methoxy, ethoxy, propoxy,
isopropoxy, butoxy, isobutoxy, pentyloxy, hexyloxy etc.), amino, mono- or di- (lower alkyl) amino (e.g. methylamino, ethylamino, dimethylamino, diethylamino etc.), carboxyl, lower alkanoyl (e.g. acetyl, propionyl etc.), lower
alkoxycarbonyl (e.g. methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, butoxycarbonyl etc.), carbamoyl,
thiocarbamoyl, mono- or di- (lower alkyl) carbamoyl (e.g.
methylcarbamoyl, ethylcarbamoyl, dimethylcarbamoyl,
diethylcarbamoyl etc.), arylcarbamoyl (e.g. phenylcarbamoyl, naphthylcarbamoyl etc.), aryloxy (e.g. phenyloxy,
naphthyloxy etc.), lower alkylcarbonylamino substituted with a halogen atom (e.g. acetylamino, trifluoroacetylamino etc.), lower alkylthio (e.g. methylthio etc.), lower
alkylsulfinyl (e.g. methylsulfinyl etc.), lower
alkylsulfonyl (e.g. methylsulfonyl etc.), arylthio (e.g. phenylthio, naphthylthio etc.), arylsulfinyl (e.g. phenylsulfinyl, naphthylsulfinyl etc.), arylsulfonyl (e.g. phenylsulfonyl, naphthylsulfonyl etc.) and the like.
Preferable examples of the "lower alkylthio lower alkyl group" in the "lower alkylthio lower alkyl group optionally substituted with one or more substituents" represented by R1 include methylthiomethyl, ethylthiomethyl, 2-πιethylthioethyl, 2-ethylthioethyl, 3-methylthiopropyl, 3- ethylthiopropyl, 4-methylthiobutyl, 4-ethylthiobutyl, 5- methylthiopentyl, 5-ethylthiopentyl, β-methylthiohexyl, 6- ethylthiohexyl and the like, and
preferable examples of the "substituent" of the "one or more substituents" in the "lower alkylthio lower alkyl group optionally substituted with one or more substituents" include a halogen atom (fluorine atom, chlorine atom, bromine atom, iodine atom) , nitro, cyano, hydroxyl, lower cycloalkyl optionally substituted with a halogen atom (e.g. cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl etc.), lower alkoxy (e.g. methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, pentyloxy, hexyloxy etc.), amino, mono- or di- (lower alkyl) amino (e.g. methylamino, ethylamino, dimethylamino, diethylamino etc.), carboxyl, lower alkanoyl (e.g. acetyl, propionyl etc.), lower alkoxycarbonyl (e.g. methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl,
butoxycarbonyl etc.), carbamoyl, thiocarbamoyl, mono- or di- (lower alkyl) carbamoyl (e.g. methylcarbamoyl, ethylcarbamoyl, dimethylcarbamoyl, diethylcarbamoyl etc.), arylcarbamoyl (e.g. phenylcarbamoyl, nap'hthylcarbamoyl etc.), aryl (e.g. phenyl, naphthyl etc.), aryloxy (e.g. phenyloxy, naphthyloxy etc.), lower alkylcarbonylamino optionally substituted with a halogen atom (e.g.
acetyl'amino, trifluoroacetylamino etc.), lower alkylthio (e.g. methylthio etc.), lower alkylsulfinyl (e.g.
methylsulfinyl etc.), lower alkylsulfonyl (e.g.
methylsulfonyl etc.), arylthio (e.g. phenylthio,
naphthylthio etc.), arylsulfinyl (e.g. phenylsulfinyl, naphthylsulfinyl etc.), arylsulfonyl (e.g. phenylsulfonyl, naphthylsulfonyl etc.) and the like.
Preferable examples of the "lower alkylsulfinyl lower alkyl group" in the "lower alkylsulfinyl lower alkyl group optionally substituted with one or more substituents" represented by R1 include methylsulfinylmethyl,
ethylsulfinylmethyl, 2-methylsulfinylethyl, 2- ethylsulfinylethyl, 3-methylsulfinylpropyl, 3- ethylsulfinylpropyl, 4-methylsulfinylbutyl, 4- ethylsulfinylbutyl, 5-methylsulfinylpentyl, 5- ethylsulfinylpentyl, 6-methylsulfinylhexyl, 6- ethylsulfinylhexyl and the like, and
preferable examples of the "substituent" of the "one or more substituents" in the "lower alkylsulfinyl lower alkyl group optionally substituted with one or more substituents" include the same substituent as the
"substituent" exemplified for the "lower alkylthio lower N alkyl group optionally substituted with one or more
substituents" .
Preferable examples of the "lower alkylsulfonyl lower alkyl group" in the "lower alkylsulfonyl lower alkyl group optionally substituted with one or more substituents" represented by R1 include methylsulfonylmethyl,
ethylsulfonylmethyl, 2-methylsulfonylethyl, 2- ethylsulfonylethyl, 3-methylsulfonylpropyl, 3- ethylsulfonylpropyl, 4-methylsulfonylbutyl, 4- ethylsulfonylbutyl, 5-methylsulfonylpentyl, 5- ethylsulfonylpentyl, 6-methylsulfonylhexyl, 6- ethylsulfonylhexyl and the like, and
preferable examples of the "substituent" of the "one or more substituents" in the "lower alkylsulfonyl lower alkyl group optionally substituted with one or more
substituents" include the same substituent as the
"substituent" exemplified for the "lower alkylthio lower alkyl group optionally substituted with one or more
substituents" .
Preferable examples of the "lower alkylamino lower alkyl group" in the "mono or dilower alkylamino lower alkyl group optionally substituted with one or more substituents" represented by R1 include methylaminomethyl, dimethylaminomethyl, methylethylaminomethyl, 2- (methylamino) ethyl, 2- (dimethylamino) ethyl, 3- (methylamino) propyl, 3- (dimethylamino) propyl, 3- (ethylamino) propyl, 4- (methylamino) butyl, A- (dimethylamino) butyl, 5- (methylamino) pentyl, 5- (dimethylamino) pentyl, 6- (methylamino) hexyl, 6- (dimethylamino) hexyl and the like, and
preferable examples of the "substituent" of the "one or more substituents" in the "mono or dilower alkylamino lower alkyl group optionally substituted with one or more substituents" include a halogen atom (fluorine atom,
chlorine atom, bromine atom, iodine atom) , nitro, cyano, hydroxyl, lower cycloalkyl optionally substituted with a halogen atom (e.g. cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl etc.), lower alkoxy (e.g. methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, pentyloxy, hexyloxy etc.), amino, mono- or di- (lower alkyl) amino (e.g.
methylamino, ethylamino, dimethylamino, diethylamino etc.), carboxyl, lower alkanoyl (e.g. acetyl, propionyl etc.), lower alkoxycarbonyl (e.g. methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, butoxycarbonyl etc.), carbamoyl,
thiocarbamoyl, mono- or di- (lower alkyl) carbamoyl (e.g.
methylcarbamoyl, ethylcarbamoyl, dimethylcarbamoyl,
biethylcarbamoyl etc.), arylcarbamoyl (e.g. phenylcarbamoyl, naphthylcarbamoyl etc.), aryl (e.g. phenyl, naphthyl etc.), aryloxy (e.g. phenyloxy, naphthyloxy etc.), lower
alkylcarbonylamino optionally substituted with a halogen atom (e.g. acetylamino, trifluoroacetylamino etc.), lower alkylthio (e.g. methylthio etc.), lower alkylsulfinyl (e.g. methylsulfinyl etc.), lower alkylsulfonyl (e.g.
methylsulfonyl etc.), arylthio (e.g. phenyltyhio,
naphthylthio etc.), arylsulfinyl (e.g. phenylsulfinyl, naphthylsulfinyl etc.), arylsulfonyl (e . g. - phenylsulfonyl, naphthylsulfonyl etc.) and the like.
Preferable examples of the "lower alkanoyl group" in the "lower alkanoyl group optionally substituted with one or more substitutents" represented by R1 include acetyl, propionyl, butyryl, isobutyryl, valeryl, isovaleryl, pivaloyl, pentanoyl, hexanoyl and the like, and
preferable examples of the "substituent" of the "one or more substituents" in' the "lower alkanoyl group
optionally substituted with one or more substitutents" include a halogen atom (fluorine atom, chlorine atom, bromine atom, iodine atom) , nitro, cyano, hydroxyl, lower cycloalkyl optionally substituted with a halogen atom (e.g. cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl etc.), lower alkoxy (e.g. methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, pentyloxy, hexyloxy etc.), amino, mono- or di- (lower alkyl) amino (e.g. methylamino, ethylamino, dimethylamino, diethylamino etc.), carboxyl, lower alkanoyl (e.g. acetyl, propionyl etc.), lower alkoxycarbonyl (e.g. methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl,
butoxycarbonyl etc.), carbamoyl, thiocarbamoyl, mono- or di- (lower alkyl) carbamoyl (e.g. methylcarbamoyl,
ethylcarbamoyl, dimethylcarbamoyl, diethylcarbamoyl etc.), arylcarbamoyl (e.g. phenylcarbamoyl, naphthylcarbamoyl etc.), aryl (e.g. phenyl, naphthyl etc.), aryloxy (e.g. phenyloxy, naphthyloxy etc.), lower alkylcarbonylamino optionally substituted with a halogen atom (e.g.
acetylamino, trifluoroacetylamino etc.), lower alkylthio (e.g. methylthio etc.), lower alkylsulfinyl (e.g.
methylsulfinyl etc.), lower alkylsulfonyl (e.g.
methylsulfonyl etc.), arylthio (e.g. phenylthio,
naphthylthio etc.), arylsulfinyl (e.g. phenylsulfinyl, naphthylsulfinyl etc.), arylsulfonyl (e.g. phenylsulfonyl, naphthylsulfonyl etc.) and-the like. Examples of the "lower alkanoyl group optionally substituted with one or more substituents" include specifically, trifluoroacetyl, bromoacetyl, methylthioacetyl, methylsulfinylacetyl, and methylsulfonylacetyl .
Preferable examples of the "lower alkoxycarbonyl group" in the "lower alkoxycarbonyl group optionally substituted with one or more substituents" represented by R1 include methoxycarbonyl, ethoxycarbonyl,
propyloxycarbonyl, isopropyloxycarbonyl, butoxycarbonyl, tert-butoxycarbonyl, pentyloxycarbonyl and hexyloxycarbonyl, and
preferable examples of the "substituent" of the "one or more substituents" in the "lower alkoxycarbonyl group optionally substituted with one or more substituents" include a halogen atom (fluorine atom, chlorine atom, bromine atom, iodine atom) , nitro, cyano, hydroxyl, lower cycloalkyl optionally substituted with a halogen atom (e.g. cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl etc.), lower alkoxy (e.g. methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, pentyloxy, hexyloxy etc.), amino, mono- or di- (lower alkyl) amino (e.g. methylamino, ethylamino, dimethylamino, diethylamino etc.), carboxyl, lower alkanoyl (e.g. acetyl, propionyl etc.), lower alkoxycarbonyl (e.g. methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl,
butoxycarbonyl etc.), carbamoyl, thiocarbamoyl, mono- or di- (lower alkyl) carbamoyl (e.g. methylcarbamoyl,
ethylcarbamoyl, dimethylcarbamoyl, diethylcarbamoyl etc.), arylcarbamoyl (e.g. phenylcarbamoyl, naphthylcarbamoyl etc.), aryloxy (e.g. phenyloxy, naphthyloxy etc.), lower alkylcarbonylamino optionally substituted with a halogen atom (e.g. acetylamino, trifluoroacetylamino etc.), lower alkylthio (e.g. methylthio etc.), lower alkylsulfinyl (e.g. methylsulfinyl etc.), lower alkylsulfonyl (e.g.
methylsulfonyl etc.), arylthio (e.g. phenylthio, naphthylthio etc.), arylsulfinyl (e.g. phenylsulfinyl, naphthylsulfinyl etc.), arylsulfonyl (e.'g. phenylsulfonyl, naphthylsulfonyl etc.) and the like.
Preferable examples of the "aryloxycarbonyl group" in the "aryloxycarbonyl group optionally substituted with one or more substituents" represented by R1 include
phenoxycarbonyl, and naphthyloxycarbonyl, and
preferable examples of the "substituent" of the "one or more substituents" in the "aryloxycarbonyl group
optionally substituted with one or more substituents" include a halogen atom (fluorine atom, chlorine atom, bromine atom, iodine atom) , nitro, cyano, hydroxyl, lower alkyl substituted with a halogen atom (e.g. chloromethyl, difluoromethyl, trichloromethyl, trifluoromethyl, 2- bromoethyl, 2, 2, 2-trifluoroethyl, pentafluoroethyl, 3,3,3- trifluoropropyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, 4 , 4 , 4-trifluorobutyl, 5, 5, 5-trifluoropentyl, 6, 6, 6-trifluorohexyl etc.), lower cycloalkyl optionally substituted with a halogen atom (e.g. cyclopropyl,
cyclobutyl, cyclopentyl, cyclohexyl etc.), lower alkoxy (e.g. methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, pentyloxy, hexyloxy etc. ) , amino, mono- or di- ( lower alkyl) amino (e.g. methylamino, ethylamino,
dimethylamino, diethylamino etc.), carboxyl, lower alkanoyl (e.g. acetyl, propionyl etc.), lower alkoxycarbonyl (e.g. methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl,
butoxycarbonyl etc.), carbamoyl, thiocarbamoyl, mono- or di- (lower alkyl) carbamoyl (e.g. methylcarbamoyl,
ethylcarbamoyl, dimethylcarbamoyl, diethylcarbamoyl etc.), arylcarbamoyl (e.g. phenylcarbamoyl, naphthylcarbamoyl etc.), aryloxy (e.g. phenyloxy, naphthyloxy etc.), lower alkylcarbonylamino optionally substituted with a halogen atom (e.g. acetylamino, trifluoroacetylamino etc.), lower alkylthio (e.g. methylthio etc.), lower alkylsulfinyl (e.g. methylsulfinyl etc.), lower alkylsulfonyl (e.g.
methylsulfonyl etc.), arylthio (e.g. phenylthio,
naphthylthio etc.), arylsulfinyl (e.g. phenylsulfinyl, naphthylsulfinyl etc.), arylsulfonyl (e.g. phenylsulfonyl, naphthylsulfonyl etc.) and the like.
Preferable examples of the "aryl lower alkoxycarbonyl group" in the "aryl lower alkoxycarbonyl group optionally substituted with one or more substituents" represented by R1 include benzyloxycarbonyl, phenethyloxycarbonyl,
anthracenylmethyloxycarbonyl and the like, and
preferable examples of the "substituent" of the "one or more substituents" in the "aryl lower alkoxycarbonyl group optionally substituted with one or more substituents" include a halogen atom (fluorine atom, chlorine atom, bromine atom, iodine atom) , nitro, cyano, hydroxyl, lower alkyl substituted with a halogen atom (e.g. chloromethyl, difluoromethyl, trichloroπiethyl, trifluoromethyl, 2- bromoethyl, 2, 2, 2-trifluoroethyl, pentafluoroethyl, 3,3,3- trifluoropropyl, 4 , 4 , 4 -trifluorobutyl, 5,5,5- trifluoropentyl, 6, 6, β-trifluorohexyl etc.) , lower
cycloalkyl optionally substituted with a halogen atom (e.g. cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl etc.), lower alkoxy (e.g. methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, pentyloxy, hexyloxy etc.), amino, mono- or di- (lower alkyl) amino (e.g. methylamino, ethylamino, dimethylamino, diethylamino etc.), carboxyl, lower alkanoyl (e.g. acetyl, propionyl etc.), lower alkoxycarbonyl (e.g. methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl,
butoxycarbonyl etc.), carbamoyl, thiocarbamoyl, mono- or di- (lower alkyl) carbamoyl (e.g. methylcarbamoyl,
ethylcarbamoyl, dimethylcarbamoyl, diethylcarbamoyl etc.), arylcarbamoyl (e.g. phenylcarbamoyl, naphthylcarbamoyl etc.), aryloxy '(e.g. phenyloxy, naphthyloxy etc.), lower alkylcarbonylamino optionally substituted with a halogen atom (e.g. acetylamino, trifluoroacetylamino etc.), lower alkylthio (e.g. methylthio etc.), lower alkylsulfinyl (e.g. methylsulfinyl etc.), lower alkylsulfonyl (e.g.
methylsulfonyl etc.), arylthio (e.g. phenylthio,
naphthylthio etc.), arylsulfinyl (e.g. phenylsulfinyl, naphthylsulfinyl etc.), arylsulfonyl (e.g. phenylsulfonyl, naphthylsulfonyl etc.) and the like. Preferable examples of the "substituent" of the "one or more substituent" in the "carbamoyl group optionally substituted with one or more substituents" represented by R1 include lower alkyl optionally substituted with a halogen atom (e.g. methyl, ethyl, 2-bromoethyl, 2,2,2- trifluoroethyl, propyl, 3, 3, 3-trifluoropropyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, 4,4,4- trifluorobutyl, pentyl, isopentyl, neopentyl, 5,5,5- trifluoropentyl, hexyl, 6, 6, 6-trifluorohexyl etc.), lower cycloalkyl optionally substituted with a halogen atom (e.g. cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl etc.), lower alkanoyl (e.g. acetyl, propionyl etc.), lower
alkoxycarbonyl (e.g. methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, butoxycarbonyl etc.), aryl (e.g. phenyl, naphthyl etc.) and the like, and
preferable examples' of the "carbamoyl group optionally substituted with one or more substituents" include a dimethylcarbamoyl group.
Preferable examples of the "substituent" of the "one or more substituents" in the "thiocarbamoyl group
optionally substituted with one or more substituents" represented by R1 include lower alkyl optionally
substituted with a halogen atom (e.g. methyl, ethyl, 2- bromoethyl, 2, 2, 2-trifluoroethyl, propyl, 3,3,3- trifluoropropyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, 4 , 4 , 4-trifluorobutyl, pentyl, isopentyl, neopentyl, 5, 5, 5-trifluoropentyl, hexyl, 6,6,6- trifluorohexyl etc.), lower cycloalkyl optionally
substituted with a halogen atom (e.g. cyclopropyl,
cyclobutyl, cyclopentyl, cyclohexyl etc. ) , lower alkanoyl (e.g. acetyl, ~ propionyl etc.), lower alkoxycarbonyl (e.g. methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl,
butoxycarbonyl etc.), aryl (e.g. phenyl, naphthyl etc.) and the like.
Preferable examples of the "lower alkoxyoxalyl group" in the "lower alkoxyoxalyl group optionally substituted withx,one or more substituents" represented by R1 include methoxyoxalyl, ethoxyoxalyl, propoxyoxalyl,
isopropoxyoxalyl, botoxyoxalyl, isobutoxyoxalyl, tert- butoxyoxalyl, pentyloxyoxalyl, tert-pentyloxyoxalyl, neo- pentyloxyoxalyl, hexyloxyoxalyl, isohexyloxyoxalyl and the like, and
preferable examples of the "substituent" of the "one or more substituents" in the "lower alkoxyoxalyl group optionally substituted with one or more substituents" include a halogen atom (fluorine atom, chlorine aton, bromine atom, iodine atom) , nitro, cyano, hydroxyl, lower cycloalkyl optionally substituted with a halogen atom (e.g. cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, etc.), lower alkoxy (e.g. methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, pentyloxy, hexyloxy etc.), amino, mono- or di- (lower alkyl) amino (e.g. methylamino, ethylamino, dimethylamino, diethylamino etc.), carboxyl, lower alkanoyl (e.g. acetyl, propionyl etc.), lower alkoxycarbonyl (e.g. methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl,
butoxycarbonyl etc.), carbamoyl, thiocarbamoyl, mono- or di- (lower alkyl) carbamoyl (e.g. methylcarbamoyl,
ethylcarbamoyl, dimethylcarbamoyl, diethylcarbamoyl etc.), arylcarbamoyl (e.g. phenylcarbamoyl, naphthylcarbamoyl etc.), aryloxy (e.g. phenyloxy, naphthyloxy etc.), lower alkylcarbonylamino optionally substituted with a halogen atom-, (e.g. acetylamino, trifluoroacetylamino etc.), lower alkylthio (e.g. methylthio etc.), lower alkylsulfinyl (e.g. methylsulfinyl etc.), lower alkylsulfonyl (e.g.
methylsulfonyl etc.), arylthio (e.g. phenylthio,
naphthylthio etc.), arylsulfinyl (e.g. phenylsulfinyl, naphthyl sulfinyl etc.), arylsulfonyl (e.g. phenylsulfonyl, naphthylsulfonyl etc.) and the like.
Preferable examples of the "aryl lower alkoxyoxalyl group" in the "aryl lower alkoxyoxalyl group optionally substituted with one or more substituents" represented by R1 include benzyloxyoxalyl and the like, and
preferable examples of the "substituent" of the "one or more substituents" in the "aryl lower alkoxyoxalyl group optionally substituted with one or more substituents" include a halogen atom (fluorine atom, chlorine atom, bromine atom, iodine atom) , nitro, cyanό, hydroxyl, lower alkyl substituted with a halogen atom (e.g. chloromethyl, difluoromethyl, trichloromethyl, trifluoromethyl, 2- bromoethyl, 2, 2, 2-trifluoroethyl, pentafluoroethyl, 3,3,3- trifluoropropyl, 4 , 4 , 4-trifluorobutyl, 5,5,5- trifluoropentyl, 6, 6, 6-trifluorohexyl etc.), lower
cycloalkyl group optionally substituted with a halogen atom (e.g. cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl etc.), lower alkoxy (e.g. methoxy, ethoxy, propoxy,
isopropoxy, butoxy, isobutoxy, pentyloxy, hexyloxy etc.), amino, mono- or di- (lower alkyl) amino (e.g. methylamino, ethylamino, dimethylamino, diethylamino etc.), carboxyl, lower alkanoyl (e.g. acetyl, propionyl etc.), lower
alkoxycarbonyl (e.g. methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, butoxycarbonyl etc.), carbamoyl,
thiocarbamoyl, mono- or di- (lower alkyl) carbamoyl (e.g.
methylcarbamoyl, ethylcarbamoyl, dimethylcarbamoyl,
diethylcarbamoyl etc.), arylcarbamoyl (e.g. phenylcarbamoyl, naphthylcarbamoyl etc.), aryloxy (e.g. phenyloxy,
naphthyloxy etc.), lower alkylcarbonylamino optionally substituted with a halogen atom (e.g. acetylamino,
trifluoroacetylamino etc.), lower alkylthio (e.g.
methylthio etc.), lower alkylsulfinyl (e.g. methylsulfinyl etc.), lower alkylsulfonyl (e.g. methylsulfonyl etc.), arylthio (e.g. phenylthio, naphthylthio etc.), arylsulfinyl (e.g. phenylsulfinyl, naphthylsulfinyl etc.), arylsulfonyl (e.g. phenylsulfonyl, naphthylsulfonyl etc.) and the like.
Preferable examples of the "aryloxyoxalyl group" in the "aryloxyoxalyl group optionally substituted with one or more substituents" represented by R1 include phenoxyoxalyl and the like, and
preferable examples of the "substituent" of the "one or more substituents" in the "aryloxyoxalyl group
optionally substituted with one or more substituents" include a halogen atom (fluorine atom, chlorine atom, bromine atom, iodine atom) , nitro, cyano, hydroxyl, lower alkyl substituted with a halogen atom (e.g. chloromethyl, difluoromethyl, trichloromethyl, trifluoromethyl, 2- bromoethyl, 2, 2, 2-trifluoroethyl, pentafluoroethyl, 3,3,3- trifluoropropyl, 4 , 4 , 4-trifluorobutyl, 5,5,5- trifluoropentyl, 6, 6, 6-trifluorohexyl etc.), lower
cycloalkyl group optionally substituted with a halogen atom (e.g. cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl etc.), lower alkoxy (e.g. methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, pentyloxy, hexyloxy etc.), amino, mono- or di- (lower alkyl) amino (e.g. methylamino, ethylamino, dimethylamino, diethylamino etc.), carboxyl, lower alkanoyl (e.g. acetyl, propionyl etc.), lower
alkoxycarbonyl (e.g. methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, butoxycarbonyl etc.), carbamoyl,
thiocarbamoyl, mono- or di- (lower alkyl)'carbamoyl (e.g.
methylcarbamoyl, ethylcarbamoyl, dimethylcarbamoyl,
diethylcarbamoyl etc.), arylcarbamoyl (e.g. phenylcarbamoyl, naphthylcarbamoyl etc.), aryloxy (e.g. phenyloxy,
naphthyloxy etc.), lower alkylcarbonylamino optionally substituted with a halogen atom (e.g. acetylamino,
trifluoroacetylamino etc.), lower alkylthio (e.g.
methylthio etc.), lower alkylsulfinyl (e.g. methylsulfinyl etc.), lower alkylsulfonyl (e.g. methylsulfonyl etc.), arylthio (e.g. phenylthio, naphthylthio etc.), arylsulfinyl (e.g: phenylsulfinyl, naphthylsulfinyl etc.), arylsulfonyl (e.g. phenylsulfonyl, naphthylsulfonyl etc.) and the like.
Preferable examples of the "substituent" of the "one or more substituents" in the "aminooxalyl group optionally substituted with one or more substituents" represented by R1 include lower alkyl optionally substituted with a
halogen atom (e.g. methyl, chloromethyl, difluoromethyl, trichloromethyl, trifluoromethyl, ethyl, 2-bromoethyl,
2, 2 , 2-trifluoroethyl, pentafluoroethyl, propyl, 3,3,3- trifluoropropyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, 4 , 4 , 4-trifluorobutyl, pentyl, isopentyl,
neopentyl, 5, 5, 5-trifluoropentyl, hexyl, 6,6,6- trifluorohexyl etc.), lower cycloalkyl optionally
substituted with a halogen atom (e.g. cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl etc.)/ lower alkanoyl (e.g. acetyl, propionyl etc.), lower aUcoxycarbonyl (e.g. methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl,
butoxycarbonyl etc.), aryl (e.g. phenyl, naphthyl etc.), and the like.
Preferable examples of the "lower alkoxy group" in the "lower alkoxy group optionally substituted with one or more substituents" represented by R1 include methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, tert-butoxy, pentyloxy, tert-pentyloxy, neo-pentyloxy, hexyloxy,
isohexyloxy and the like, preferably methoxy, ethoxy, propόxy, butoxy, pentyloxy, hexyloxy and isohexyloxy, and preferable examples of the "substituent" of the "one or more substituents" in the "lower alkoxy group optionally substituted with one or more substituents" include a halogen atom (fluorine atom, chlorine atom, bromine atom, iodine atom) , nitro, cyano, hydroxyl, lower cycloalkyl group optionally substituted with a halogen atom (e.g.
cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl etc.), lower alkoxy (e.g. methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, pentyloxy, hexyloxy etc.), amino, mono- or di- (lower alkyl) amino (e.g. methylamino, ethylamino, dimethylamino, diethylamino etc.), carboxyl, lower alkanoyl (e.g. acetyl, propionyl etc.), lower alkoxycarbonyl (e.g. methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, butoxycarbonyl etc.), carbamoyl, thiocarbamoyl, mono- or di- (lower alkyl) carbamoyl (e.g. methylcarbamoyl,
ethylcarbamoyl, dimethylcarbamoyl, diethylcarbamoyl etc.), arylcarbamoyl (e.g. phenylcarbamoyl, naphthylcarbamoyl etc.), aryloxy (e.g. phenyloxy, naphthyloxy etc.), lower alkylcarbonylamino optionally substituted with a halogen atom (e.g. acetylamino, trifluoroacetylamino etc.), lower alkylthio (e.g. methylthio etc.), lower alkylsulfinyl (e.g. methylsulfinyl etc.), lower alkylsulfonyl (e.g.
methylsulfonyl etc.), arylthio (e.g. phenylthio,
naphthylthio etc.), arylsulfinyl (e.g. phenylsulfinyl, naphthylsulfinyl etc.), arylsulfonyl (e.g. phenylsulfonyl, naphthylsulfonyl etc.) and the like.
Preferable examples of the "aryloxy group" in the "aryloxy group optionally substituted with one or more substituents" represented by R1 include phenoxy,
naphthyloxy, anthracenyloxy and the like, and
preferable examples of the "substituent" of the "one or more substituents" in the "aryloxy group optionally substituted with one or more substituents" include a halogen atom (fluorine atom, chlorine atom, bromine atom, iodine atom) , nitro, cyano, hydroxyl, lower cycloalkyl optionally substituted with a halogen atom (e.g.
cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl etc.), lower alkyl substituted with a halogen atom (e.g. chloromethyl, difluoromethyl, trichloromethyl, trifluoromethyl, 2-bromoethyl, 2, 2, 2-trifluoroethyl,
pentafluoroethyl, 3, 3, 3-trifluoropropyl, 4,4,4- trifluorobutyl, 5, 5, 5-trifluoropentyl, hexyl, 6,6,6- trifluorohexyl etc.), lower alkoxy (e.g. methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, pentyloxy, hexyloxy etc.), amino, mono- or di- (lower alkyl) amino (e.g.
methylamino, ethylamino, dimethylamino, diethylamino etc.), carboxyl, lower alkanoyl (e.g. acetyl, propionyl etc.), lower alkoxycarbonyl (e.g. methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, butoxycarbonyl etc.), carbamoyl,
thiocarbamoyl, mono- or di- (lower alkyl) carbamoyl (e.g.
methylcarbamoyl, ethylcarbamoyl, dimethylcarbamoyl,
diethylcarbamoyl etc.), arylcarbamoyl (e.g. phenylcarbamoyl, naphthylcarbamoyl etc.), aryloxy (e.g. phenyloxy,
naphthyloxy etc.), lower alkylcarbonylamino optionally substituted with a halogen atom (e.g. acetylamino,
trifluoroacetylamino etc.), lower alkylthio (e.g.
methylthio etc.), lower alkylsulfinyl (e.g. methylsulfinyl etc.), lower alkylsulfonyl (e.g. methylsulfonyl etc.), arylthio (e.g. phenylthio, naphthylthio etc.), arylsulfinyl (e.g. phenylsulfinyl, naphthylsulfinyl etc.), arylsulfonyl (e.g. phenylsulfonyl, naphthylsulfonyl etc.) and the like.
Preferable examples of the "aryl lower alkoxy group" in the "aryl lower alkoxy group optionally substituted with one or more substituents" represented by R1 include
benzyloxy, naphtylmethyloxy, anthracenyϊmethyloxy and the like, and
preferable examples of the "substituent" of the "one or more substituents" in the "aryl lower alkoxy group optionally substituted with one or more substituents" include a halogen atom (fluorine atom, chlorine atom, bromine atom, iodine atom) , nitro, cyano, hydroxyl, lower alkyl substituted with a halogen atom (e.g. chloromethyl, difluoromethyl, trichloromethyl, trifluoromethyl, 2- bromoethyl, 2, 2, 2-trifluoroethyl, pentafluoroethyl, 3,3,3- trifluoropropyl, 4 , 4 , 4-trifluorobutyl, 5,5,5- trifluoropentyl, 6, 6, 6-trifluorohexyl etc.), lower
cycloalkyl optionally substituted with a halogen atom (e.g. cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl etc.), lower alkoxy (e.g. methoxy; ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, pentyloxy, hexyloxy etc.), amino, mono- or di- (lower alkyl) amino (e.g. methylamino, ethylamino, dimethylamino, diethylamino etc.), carboxyl, lower alkanoyl (e.g. acetyl, propionyl etc.), lower alkoxycarbonyl (e.g. methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl,
butoxycarbonyl etc.), carbamoyl, thiocarbamoyl, mono- or di- (lower alkyl) carbamoyl (e.g. methylcarbamoyl,
ethylcarbamoyl, dimethylcarbamoyl, diethylcarbamoyl etc.), arylcarbamoyl (e.g. phenylcarbamoyl, naphthylcarbamoyl etc.), aryloxy (e.g. phenyloxy, naphthyloxy etc.), lower alkylcarbonylamino optionally substituted with a halogen atom (e.g. acetylamino, trifluoroacetylamino etc.), lower alkylthio (e.g. methylthio etc.), lower alkylsulfinyl (e.g. methylsulfinyl etc.), lower alkylsulfonyl (e.g.
methylsulfonyl etc.), arylthio (e.g. phenylthio,
naphthylthio etc.), arylsulfinyl (e.g. phenylsulfinyl, naphthylsulfinyl etc.), arylsulfonyl (e . g. , phenylsulfonyl, naphthylsulfonyl etc.) and the like.
Preferable examples of the "substituent" of the "one or more substituents" in the "amino group optionally substituted with one or more substituents" represented by R1 include lower alkyl optionally substituted with a halogen atom (e.g. methyl, ethyl, 2-bromoethyl, 2,2,2- trifluoroethyl, propyl, 3, 3, 3-trifluoropropyl, isopropyl, butyl, isobutyl, sec-butyl,- tert-butyl, 4,4,4- trifluorobutyl, pentyl, isopentyl, neopentyl, 5,5,5- trifluoropentyl, hexyl, 6, 6, 6-trifluorohexyl etc.), lower cycloalkyl optionally substituted with a halogen atom (e.g. cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl etc.), lower alkanoyl (e.g. acetyl, propionyl etc.), lower
alkoxycarbonyl (e.g. methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, butoxycarbonyl etc.), carbamoyl,
thiocarbamoyl, mono- or di- (lower alkyl) carbamoyl (e.g.
methylcarbamoyl, ethylcarbamoyl, dimethylcarbamoyl, diethylcarbamoyl etc.), arylcarbamoyl (e.g. phenylcarbamoyl, naphthylcarbamoyl etc.), aryl (e.g. pheriyl, naphthyl etc.) and the like.
Preferable examples of the "heterocyclic group" in the "heterocyclic group optionally substituted with one or more substituents"* represented by R1 include an "aromatic
monocyclic heterocyclic group",
examples of the aromatic monocyclic heterocyclic group include 5-membered aromatic monocyclic heterocyclic groups such as 2-furyl, 3-furyl, 2-thienyl, 3-thienyl, 2-pyrrolyl, 3-pyrrolyl, 2-oxazolyl, 4-oxazolyl, 5-oxazolyl, 3- isoxazolyl, 4-isoxazolyl, 5-isoxazolyl, 2-thiazolyl, 4- thiazolyl, 5-thiazolyl, 3-isothiazolyl, 4-isothiazolyl, 5- isothiazolyl, 2-imidazolyl, 4-imidazolyl, 5-imidazolyl, 3- pyrazolyl, 4-pyrazolyl, 5-pyrazolyl, 1, 2, 3-oxadiazol-4-yl, 1, 2, 3-oxadiazol-5-yl, 1, 2, 4-oxadiazol-5-yl, 1,2,4- oxadiazol-3-yl, 1, 3, 4-oxadiazol-2-yl, furazanyl, 1,2,3- thiadiazol-4-yl, 1, 2, 3-thiadiazol-5-yl, 1, 2 , 4-thiadiazol-3- yl, 1,2, 4-thiadiazol-5-yl, 1, 3, 4-thiadiazol-2-yl, IH-I, 2, 3- triazol-4-yl, IH-I, 2, 3-triazol-5-yl, IH-I, 2, 4-triazol-3-yl, lH-tetrazol-5-yl and the like, and
6-membered aromatic monocyclic heterocyclic groups such as 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyrimidinyl, 4- pyrimidinyl, 5-pyrimidinyl, 3-pyridazinyl, 4-pyridazinyl, 2-pyrazinyl, 1, 2 , 4-triazin-3-yl, 1, 2, 4-triazin-5-yl, 1,2,4- triazin-6-yl, 1, 3, 5-triazin-2-yl and the like, and
preferable examples of the "substituent" of the "one or more substituents" in the "heterocyclic group optionally substituted with one or more substituents" include a
halogen atom (fluorine atom, chlorine atom, bromine atom, iodine atom) , lower alkyl optionally substituted with a halogen atom (e.g. methyl, chloromethyl, dichloromethyl, trifluoromethyl, ethyl, 2, 2, 2-trifluoromethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, hexyl etc.), lower cycloalkyl (e.g. cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl etc.), aryl lower alkyl (e.g.
benzyl, α-methylbenzyl, phenethyl etc.), aryl (e.g. phenyl group, naphthyl group etc.), lower alkoxy (e.g. methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, sec-butoxy, tert-butoxy etc.), aryloxy (e.g. phenoxy etc.), formyl, lower alkanoyl group (e.g. acetyl, propionyl, butyryl, isobutyryl etc.), arylcarbonyl (e.g. benzoyl, naphthoyl etc.), formyloxy, lower alkanoyloxy (e.g. acetyloxy,
propionyloxy, butyryloxy, isobutyryloxy etc.),
arylcarbonyloxy (e.g. benzoyloxy, naphthoyloxy etc.), carboxyl, lower alkoxycarbonyl (e.g. methoxycarbonyl, ethoxycarbonyl, propyloxycarbonyl, isopropyloxycarbonyl, butoxycarbonyl, isobutoxycarbonyl, tert-butoxycarbonyl etc.), aryl lower alkoxycarbonyl (e.g. benzyloxycarbonyl etc.), carbamoyl, amino, mono- or di- (lower alkyl) amino (e.g. mono (lower alkyl) amino such as methylamino,
ethylamino, propylamino, isopropylamino and butylamino, as well as di (lower alkyl) amino such as dimethylamino,
diethylamino, dipropylamino, diisopropylamino, dibutylamino and methylethylamino) , a 3- to 6- membered cyclic amino group (e.g. aziridinyl, azetidinyl, pyrrodinyl, pyrrolinyl, pyrrolyl, imidazolyl, pyrazolyl, imidazolidinyl, piperidyl, morpholinyl, dihydropyridyl, N-methylpiperazinyl, N- ethylpiperazinyl etc.), nitro, cyano, mono or di (lower alkyl) sulfamoyl group (e.g. mono (lower alkyl) sulfamoyl such as N-methylsulfamoyl, N-ethylsulfamoyl, N-propylsulfamoyl, N-isόpropylsulfamoyl, and N-butylsulfamoyl, as well as di (lower alkyl) sulfamoyl such as N, N-dimethylsulfamoyl, N, N-diethylsulfamoyl, N, N, -dipropylsulfamoyl, and N, N- dibutylsulfamoyl) , lower alkylthio (e.g. methylthio, ethylthio, propylthio, isopropylthio, butylthio, sec- butylthio and tert-butylthio) , arylthio (e.g. phenylthio, naphthylthio etc.), lower alkylsulfinyl (e.g.
methylsulfinyl, ethylsulfinyl, propylsulfinyl,
butylsulfinyl etc.), arylsulfinyl (e.g. phenylsulfinyl, naphthylsulfinyl etc.), lower alkylsulfonyl (e.g.
methylsulfonyl, ethylsulfonyl, propylsulfonyl,
butylsulfonyl etc.), arylsulfonyl (e.g. phenylsulfonyl, naphthylsulfonyl etc.).
Examples of the "lower alkylene" in the "lower alkylene optionally substituted with one or more halogen atoms" represented by R2 include methylene, ethylene, trimethylene, hexamethylene, pentamethylene, and
hexamethylene, preferably a "C1-C6 alkylene group" such as methylene, ethylene, trimethylene, and hexamethylene, and examples" of the "halogen atom" of the "one or more halogen atoms" in the "lower alkylene optionally
substituted with one or more halogen atoms" include a fluorine atom, a chlorine atom, a bromine atom, and an iodine atom.
Preferable examples of the "lower alkanoyl group" in the '"lower alkanoyl group optionally substituted with one or more substituents" represented by R3 include acetyl, propionyl, butyryl, isobutyryl, valeryl, isovaleryl, pivaloyl, pentanoyl, hexanoyl and the like, and
preferable examples of the "substituent" of the "one or more substituents" in the "lower alkanoyl group
optionally substituted with one or more substituents" include a halogen atom (fluorine atom, chlorine atom, bromine atom, iodine atom) , nitro, cyano, hydroxyl, lower alkoxy (e.g. methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, pentyloxy, hexyloxy etc.), amino, mono- or di- (lower alkyl) amino (e.g. methylamino, ethylamino,
dimethylamino, diethylamino etc.), carboxyl, lower alkanoyl (e.g. acetyl, propionyl etc.), lower alkoxycarbonyl (e.g. methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl,
butoxycarbonyl etc.), carbamoyl, thiocarbamoyl, mono- or di- (lower alkyl) carbamoyl (e.g. methylcarbamoyl,
ethylcarbamoyl, dimethylcarbamoyl, diethylcarbamoyl etc.), arylcarbamoyl (e.g. phenylcarbamoyl, naphthylcarbamoyl etc.), aryl (e.g. phenyl, naphtyl etc.), aryloxy (e.g. phenyloxy, naphthyloxy etc.), lower alkylcarbonylamino optionally substituted with a halogen atom (e.g.
acetylamino, trifluoroacetylamino etc.), lower alkylthio (e.g. methylthio etc.), lower alkylsulfinyl (e.g.
methylsulfinyl etc.), lower alkylsulfonyl (e.g.
methylsulfonyl etc.), arylthio (e.g. phenylthio,
naphthylthio etc.), arylsulfinyl (e.g. phenylsulfinyl, naphthylsulfinyl etc.), arylsulfonyl (e.g. phenylsulfonyl, naphthylsulfonyl etc.) and the like.
Examples of the "C1-C3 alkyl group" in the "C1-C3 alkyl group optionally substituted with one or more substituents" represented by R3, R4, R5 and R6 include methyl, ethyl, n-propyl, and isopropyl, and
preferable examples of the "substituent" in the "one or more substituents" in the "C1-C3 alkyl group optionally substituted with one or more substituents" include a halogen atom (fluorine atom, chlorine atom, bromine atom, iodine atom), nitro, cyano, hydroxyl, lower alkoxy (e.g. methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, pentyloxy, hexyloxy etc.), amino, mono- or di- (lower
alkyl) amino (e.g. methylamino, ethylamino, dimethylamino, diethylamino etc.), carboxyl, lower alkanoyl (e.g. acetyl, propionyl etc.), lower alkoxycarbonyl (e.g. methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, butoxycarbonyl etc.), carbamoyl, thiocarbamoyl, mono- or di- (lower
alkyl) carbamoyl (e.g. methylcarbamoyl, ethylcarbamoyl, dimethylcarbamoyl, diethylcarbamoyl etc.),- arylcarbamoyl (e.g. phenylcarbamoyl, naphthylcarbamoyl etc.), aryloxy (e.g. phenyloxy, naphthyloxy etc.), lower
alkylcarbonylamino optionally substituted with a halogen atomMe.g. acetylamino, trifluoroacetylamino etc.), lower alkylthio (e.g. methylthio etc.), lower alkylsulfinyl (e.g. methylsulfinyl etc.), lower alkylsulfonyl (e.g.
methylsulfonyl etc.), arylthio (e.g. phenylthio,
naphthylthio etc.), arylsulfinyl (e.g. phenylsulfinyl, naphthylsulfinyl etc.), arylsulfonyl (e.g. phenylsulfonyl, naphthylsulfonyl etc.) and the like.
Preferable examples of the "lower alkenyl group" in the "lower alkenyl group optionally substituted with one or more substituents" represented by R3, R4, R5 and R6 include vinyl, allyl, isopropenyl, isobutenyl, 1-methylallyl, 2- pentenyl, 2-hexenyl and the like, and
preferable examples of the "substituent" in the "one or more substituents" in the "lower alkenyl group optionally substituted with one or more substituents" include a halogen atom (fluorine atom, chlorine atom, bromine atom, iodine atom) , nitro, cyano, hydroxyl, lower alkoxy (e.g. methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, pentyloxy, hexyloxy etc.), amino, mono- or di- (lower alkyl) amino (e.g. methylamino, ethylamino,
dimethylamino, diethylamino etc.), carboxyl, lower alkanoyl (e.g. acetyl, propionyl etc.), lower alkoxycarbonyl (e.g. methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl,
butoxycarbonyl etc.), carbamoyl, thiocarbamoyl, mono- or di- (lower alkyl) carbamoyl (e.g. methylcarbamoyl,
ethylcarbamoyl, dimethylcarbamoyl, diethylcarbamoyl etc.), arylcarbamoyl (e.g. phenylcarbamoyl, naphthylcarbamoyl etc.), aryl (e.g. phenyl, naphthyl etc.), aryloxy (e.g. phenyloxy, naphthyloxy etc.), lower alkylcarbonylamino optionally substituted with a halogen atom (e.g.
acetylamino, trifluoroacetylamino etc.), lower alkylthio (e.g. methylthio etc.), lower alkylsulfinyl (e.g.
methylsulfinyl etc.), lower alkylsulfonyl (e.g.
methylsulfonyl etc.), arylthio (e.g. phenylthio,
naphthylthio etc.), arylsulfinyl (e.g. phenylsulfinyl, naphthylsulfinyl etc.), arylsulfonyl (e.g. phenylsulfonyl, naphthylsulfonyl etc.) and the like.
Preferable examples of the "lower alkynyl group" in the "alkynyl group optionally substituted with one or more substituents" represented by R3, R4, R5 and R6 include ethynyl, 2-propynyl, 1-propynyl, 2-butyriyl, 3-butynyl, 3- pentynyl, 3-hexynyl and the like, and
preferable examples of the "substituent" in the "one or more substituents" in the "alkynyl group optionally substituted with one or more substituents" include a
halogen atom (fluorine atom, chlorine atom, bromine atom, iodine atom), nitro, cyano, hydroxyl, lower alkoxy (e.g. methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, pentyloxy, hexyloxy etc.), amino, mono- or di- (lower
alkyl) amino (e.g. methylamino, ethylamino, dimethylamino, diethylamino etc.), carboxyl, lower alkanoyl (e.g. acetyl, propionyl etc.), lower alkoxycarbonyl (e.g. methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, butoxycarbonyl etc.), carbamoyl, thiocarbamoyl, mono- or di- (lower
alkyl) carbamoyl (e.g. methylcarbamoyl, ethylcarbamoyl, dimethylcarbamoyl, diethylcarbamoyl etc.), arylcarbamoyl (e.g. phenylcarbamoyl, naphthylcarbamoyl etc.), aryl (e.g. phenyl, naphthyl etc.), aryloxy (e.g. phenyloxy,
naphthyloxy etc.), lower alkylcarbonylamino optionally substituted with a halogen atom (e.g. acetylamino,
trifluoroacetylamino etc.), lower alkylthio (e.g.
methylthio etc.), lower alkylsulfinyl (e.g. methylsulfinyl etc.), lower alkylsulfonyl (e.g. methylsulfonyl etc.), arylthio (e.g. phenylthio, naphthylthio etc.), arylsulfinyl (e.g. phenylsulfinyl, naphthylsulfinyl etc.), arylsulfonyl (e.g. phenylsulfonyl, naphthylsulfonyl e'tc.) and the like.
Preferable examples of the "aryl group" in the "aryl group optionally substituted with one or more substituents" represented by R3, R4, R5 and R6 include phenyl, mesityl, xylyl, tolyl, "naphthyl, anthracenyl and the like, and
preferable examples of the "substituent" of the "one or more substituents" in the "aryl group optionally
substituted with one or more substituents" include a halogen atom (fluorine atom, chlorine atom, bromine atom, iodine atom) , nitro, cyano, hydroxyl, lower alkyl
substituted with a halogen atom (e.g. chloromethyl, difluoromethyl, trifluoromethyl, trifluoromethyl, 2- bromoethyl, 2, 2 , 2-trifluoroethyl, pentafluoroethyl, 3,3,3- trifluoropropyl, 4 , 4 , 4-trifluorobutyl, 5,5,5- trifluoropentyl, 6, 6, β-trifluorohexyl etc.), lower alkoxy (e.g. methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, pentyloxy, hexyloxy etc.), amino, mono- or di- (lower alkyl) amino (e.g. methylamino, ethylamino,
dimethylamino, diethylamino etc.), carboxyl, lower alkanoyl (e.g. acetyl, propionyl etc.), lower alkoxycarbonyl (e.g. methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl,
butoxycarbonyl etc.), carbamoyl, thiocarbamoyl, mono- or di- (lower alkyl ) carbamoyl (e.g. methylcarbamoyl,
ethylcarbamoyl, dimethylcarbamoyl, diethylcarbamoyl etc.), arylcarbamoyl (e.g. phenylcarbamoyl, naphthylcarbamoyl etc.), aryloxy (e.g. phenyloxy, naphthyϊoxy etc.), lower alkylcarbonylamino optionally substituted with a halogen atom (e.g. acetylamino, trifluoroacetylamino etc.), lower alkylthio (e.g. methylthio etc.), lower alkylsulfinyl (e.g. methylsulfinyl etc.), lower alkylsulfonyl (e.g.
methylsulfonyl etc.), arylthio (e.g. phenylthio,
naphthylthio etc.), arylsulfinyl (e.g. phenylsulfinyl, naphthylsulfinyl etc.), arylsulfonyl (e.g. phenylsulfonyl, naphthylsulfonyl etc.) and the like.
Preferable examples of the "aryl lower alkyl group" in the "aryl lower alkyl group optionally substituted with one or more substituents" represented by R3, R4, R5 and R6 include benzyl, phenethyl and the like, and
preferable examples of the "substituent" of the "one or more substituents" in the "aryl lower alkyl group optionally substituted with one or more substituents" include a halogen atom (fluorine atom, chlorine atom, bromine atom, iodine atom) , nitro, cyano, hydroxyl, lower alkyl substituted with a halogen atom (e.g. chloromethyl, difluoromethyl, trichloromethyl, trifluoromethyl, 2- bromoethyl, 2, 2, 2-trifluoroethyl, pentafluoroethyl, 3,3,3- trifluoropropyl, 4 , 4 , 4-trifluorobutyl, 5,5,5- trifluoropentyl, 6, 6, 6-trifluorohexyl etc.), lower alkoxy (e.g. methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, pentyloxy, hexyloxy etc.), amino, mono or dilower alkylamino (e.g. methylamino, etzhylamino,
dimethylamino, diethylamino etc.), carboxyl, lower alkanoyl (e.g. acetyl, propionyl etc.), lower alkoxycarbonyl (e.g. methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl,
butoxycarbonyl etc.), carbamoyl, thiocarbamoyl, mono- or di- (lower alkyl) carbamoyl (e.g. methylcarbamoyl,
ethylcarbamoyl, dimethylcarbamoyl, diethylcarbamoyl etc.), arylcarbamoyl (e.g. phenylcarbamoyl, naphthylcarbamoyl etc.), aryloxy (e.g. phenyloxy, naphtylocy etc.), lower alkylcarbonylamino optionally substituted with a halogen atom\(e.g. acetylamino, trifluoroacetylamino etc.), lower alkylthio (e.g. methylthio etc.), lower alkylsulfinyl (e.g. methylsulfinyl etc.), lower alkylsulfonyl (e.g.
methylsulfonyl etc.), arylthio (e.g. phenylthio,
naphthylthio etc.), arylsulfinyl (e.g. phenylsulfinyl, naphthylsulfinyl etc.), arylsulfonyl (e.g. phenylsulfonyl, naphthylsulfonyl etc.) and the like.
Examples of the "R5 and R6 are taken together at the ends thereof to form together with the nitrogen atom a 3- to 7-membered nitrogen-containing heterocycle optionally having other nitrogen atom, oxygen atom or sulfur atom as a ring constituting atom" include a 1-pyrrolidinyl group, a piperidino group, a morpholino group, and a thiomorpholino group. Examples of the "halogen atom" represented by R7 include a fluorine atom, a chlorine atom, a bromine atom, and an iodine atom.
Preferable examples of the "aryl lower alkoxy group" in the "aryl lower alkoxy group optionally substituted with one or more halogen atoms" represented by R7 include benzyloxy, phenethyloxy, naphthylmethyloxy,
naphthylethyloxy, anthracenylmethyloxy and the like, and as the "halogen atom", the aforementioned "halogen atom" can be mentioned.
Preferable examples of the "lower alkanoyl group" in the "lower alkanoyl group optionally substituted with one or more halogen atoms" represented by R7 include acetyl, propionyl, butyryl, isobutyryl, pentanoyl, 2,2- dimethylpropionyl, hexanoyl and the like, and
as the "halogen atom", the aforementioned "halogen atom" can be mentioned.
Preferable examples of the "lower alkoxycarbonyl group" in the "lower alkoxycarbonyl group optionally substituted with one or more halogen atoms" represented by R7 include methoxycarbonyl, ethoxycarbonyl,
propyloxycarbonyl, isopropyloxycarbonyl, butoxycarbonyl, tert-butoxycarbonyl, pentyloxycarbonyl, hexyloxycarbonyl and the like, and
as the "halogen atom", the aforementionned "halogen atom" can be mentioned.
Preferable examples of the "aryl group" in the "aryl group optionally substituted with one or more halogen atoms" represented by R7 include phenyl, 1-naphthyl, 2- naphthyl, biphenylyl, 2-anthracenyl and the like, and
as the "halogen atom", the aforementioned "halogen atom" can be mentioned.
Preferable examples of the "aryl lower alkoxycarbonyl group" in the "aryl lower alkoxycarbonyl group optionally substituted with one or more halogen atoms" include
benzyloxycarbonyl, phenethyloxycarbonyl,
antheracenylmethyloxycarbonyl and the like, and
as the "halogen atom", the aforementioned "halogen atom" can be mentioned.
Preferable examples of the "arylcarbamoyl group" in the "arylcarbamoyl group' optionally substituted with one or more halogen atoms" represented by R7 include
phenylcarbamoyl, 1-naphthylcarbamoyl, 2-naphthylcarbamoyl, biphenylylcarbamoyl, 2-anthracenylcarbamoyl and the like, and
as the "halogen atom", the aforementioned "halogen atom" can be mentioned.
Preferable examples of the "lower alkyl group" in the "carbamoyl group optionally substituted with one or more lower alkyl groups" represented by R7 include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert- butyl, n-pentyl, sec-pentyl, isopentyl, neopentyl, n-hexyl, isohexyl and the like.
Preferable examples of the "lower alkyl group" in the "thiocarbamoyl group optionally substituted with one or more lower alkyl groups" represented by R7 include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, sec-pentyl, isopentyl, neopentyl, n- hexyl, isohexyl and the like.
Preferable examples of the "lower alkyl group" in the "amino group optionally substituted with one or more lower alkyl groups" represented by R7 include methyl, ethyl, n- propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, sec-pentyl, isopentyl, neopentyl, n-hexyl,
isohexyl and the like.
Preferable examples of the "lower alkyl group" in the "lower alkyl group optionally substituted with one or more halogen atoms" represented by R7 include methyl, ethyl, n- propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, sec-pentyl, isopentyl, neopentyl, n-hexyl,
isohexyl and the like, and
as the "halogen atom", the aforementioned "halogen atom" can be mentioned.
Preferable examples of the "lower alkoxy group" in the "lower alkoxy group optionally substituted with one or more halogen atoms" represented by R7 include methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, 'tert-butoxy, pentyloxy, tert-pentyloxy, neo-pentyloxy, hexyloxy, isohexyloxy and the like, preferably methoxy, ethoxy, propoxy, butoxy, pentyloxy, hexyloxy, and isohexyloxy, and as the "halogen atom", the aforementioned "halogen atom" can be mentioned.
Preferable examples of the "lower alkoxy lower alkoxy group" in the "lower alkoxy lower alkoxy group optionally substituted with one or more halogen atoms" represented by R7 include methoxymethoxy, ethoxymethoxy, 2-methoxymethoxy, 2-ethoxyethoxy, 3-methoxypropyloxy, 3-ethoxypropyloxy, 4- methoxybutyloxy, 4-ethoxybutyloxy, 5-methoxypentyloxy, 5- ethoxypentyloxy, 6-methoxyhexyloxy, 6-ethoxyhexyloxy and the like, and
as the "halogen atom", the aforementioned "halogen atom" can be mentioned.
Preferable examples of the "lower alkenyloxy group" in the "lower alkenyloxy group optionally substituted with one or more halogen atoms" represented by R7 include vinyloxy, allyloxy, isopropynyloxy, isobutenyloxy, 1-methylallyloxy, 2-pentenyloxy, 2-hexenyloxy and the like, and
as the "halogen atom", the aforementioned "halogen atom" can be mentioned.
Preferable examples of the "lower alkynyloxy group" in the "lower alkynyloxy group optionally substituted with one or more halogen atoms" represented by R7 include ethynyloxy, 2-propynyloxy, 1-propynyloxy, 2-butynyloxy, 3-butynyloxy, 3-pentynyloxy, 3-hexynyloxy, and the like, and
as the "halogen atom", the aforementioned "halogen atom" can be mentioned.
Preferable examples of the "lower alkanoylamino group" in the "lower alkanoylamino group optionally substituted with one or more halogen atoms" represented by R7 include acetylamino, 2-methylpropionylamino, propionylamino,
butyrylamino, isobutyrylamino, pentanoylamino, 2,2- dimethylpropionylamino, hexanoylamino and the like, and
as the "halogen atom", the aforementioned "halogen atom" can be mentioned.
Preferable examples of the "lower alkylthio group" in the "lower alkylthio group• optionally substituted with one or more halogen atoms" represented by R7 include methylthio, ethylthio, n-propylthio, isopropylthio, n-butylthio,
isobutylthio, sec-butylthio, tert-butylthio, n-pentylthio, sec-pentylthio, isopentylthio, neopentylthio, n-hexylthio, isohexylthio and the like, and
as the "halogen atom", the aforementioned "halogen atom" can be mentioned.
Preferable examples of the "lower alkenylthio group" in the "lower alkenylthio group optionally substituted with one or more halogen atoms" represented by R7 include
allylthio, isopropenylthio, isobutenylthio, 1- methylallylthio, 2-pentenylthio, 2-hexenylthio and the like, and
as the "halogen atom", the aforementioned "halogen atom" can be mentioned.
Preferable examples of the "lower alkynylthio group" in the "lower alkynylthio group optionally substituted with one or more halogen atoms" represented by R7 include 2- propynylthio, 1-propynylthio, 2-butynylthio, 3-butynylthio, 3-pentynylthio, 3-hexynylthio and the like, and
■as the "halogen atom", the aforementioned "halogen atom" can be mentioned.
Preferable examples of the "lower alkylsulfinyl group" in the "lower alkylsulfinyl group optionally substituted with one or more halogen atoms" represented by R7 include methylsulfinyl, ethylsulfinyl, n-propylsulfinyl,
isopropylsulfinyl, n-butylsulfinyl, isobutylsulfinyl, sec- butylsulfinyl, tert-butylsulfinyl, n-pentylsulfinyl, sec- pentylsulfinyl, isopentylsulfinyl, neopentylsulfinyl, n- hexylsulfinyl, isohexylsulfinyl and the like, and
as the "halogen atom", the aforementioned "halogen atom" can be mentioned.
Preferable examples of the "lower alkenylsulfinyl group" in the "lower alkenylsulfinyl group optionally substituted with one or more halogen atoms" represented by R7 include allylsulfinyl, isopropenylsul'finyl,
isobutenylsulfinyl, 1-methylallylsulfinyl, 2- pentenylsulfinyl, 2-hexenylsulfinyl and the like, and
as the "halogen atom", the aforementioned "halogen atom" can be mentioned.
Preferable examples of the "lower alkynylsulfinyl group" in the "lower alkynylsulfinyl group. optionally substituted with one or more halogen atoms" represented by R7 include 2-propynylsulfinyl, 1-propynylsulfinyl, 2- butynylsulfinyl, 3-butynylsulfinyl, 3-pentynylsulfinyl, 3- hexynylsulfinyl and the like, and
as the "halogen atom", the aforementioned "halogen atom" can be mentioned.
Preferable examples of the "lower alkylsulfonyl group" in the "lower alkylsulfonyl group optionally substituted with one or more halogen atoms" represented by R7 include methylsulfonyl, ethylsulfonyl, n-propylsulfonyl,
isopropylsulfonyl, n-butylsulfonyl, isobutylsulfonyl, sec- butylsulfonyl, tert-butylsulfonyl, n-pentylsulfonyl, sec- pentylsulfonyl, isopentylsulfonyl, neopentylsulfonyl, n- hexylsulfonyl, isohexylsulfonyl and the like, and
as the "halogen atom", the aforementioned "halogen atom" can be mentioned.
Preferable examples of the "lower alkenylsulfonyl group" in the "lower alkenylsulfonyl group optionally substituted with one or more halogen atoms" represented by R7 include allylsulfonyl, isopropenylsulfonyl,
isobutenylsulfonyl, 1-methylallylsulfonyl, 2- pentenylsulfonyl, 2-hexenylsulfonyl and the like, and
as the "halogen atom", the aforementioned "halogen atom" can be mentioned.
Preferable examples of the "lower alkynylsulfonyl group" in the "lower alkynylsulfonyl group optionally substituted with one or more halogen atoms" represented by R7 include 2-propynylsulfonyl, 1-propynylsulfonyl, 2- butynylsulfonyl, 3-butynylsulfonyl, 3-pentynylsulfonyl, 3- hexynylsulfonyl and the like, and
as the "halogen atom", the aforementioned "halogen atom" can be mentioned.
Preferable examples of the "lower alkoxy lower
alkylthio group" in the "lower alkoxy lower alkylthio group optionally substituted with one or more halogen atoms" represented by R7 include methoxymethylthio,
ethoxymethylthio, 2-methoxyethylthio, 2-ethoxyethylthio, 3- methoxypropylthio, 3-ethoxypropylthio, 4-methoxybutylthio, 4-ethoxybutylthio, 5-methoxypentylthio, 5-ethoxypentylthio, 6-methoxyhexylthio, 6-ethoxyhexylthio and the like, and
as the "halogen atom", the aforementioned "halogen atom" can be mentioned. Examples of the "halogen atom" which is a substituent of E include a fluorine atom, a chlorine1 atom, a bromine atom, and an iodine atom.
Preferable examples of the "lower alkyl group" in the "lower alkyl group optionally substituted with one or more halogen atoms" which is a substituent of E include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, sec-pentyl, isopentyl, neopentyl, n- hexyl, isohexyl and the like, and
as the "halogen atom", the aforementioned "halogen atom" can be mentioned.
-Preferable examples of the "lower alkoxy group" in the "lower alkoxy group optionally substituted with one or more halogen atoms" which is a substituent of E include methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, tert-butoxy, pentyloxy, tert-pentyloxy, 'neo-pentyloxy, hexyloxy,
isohexyloxy and the like, preferably methoxy, ethoxy, propoxy, butoxy, pentyloxy, hexyloxy, and isohexyloxy, and as the "halogen atom", the aforementioned "halogen atom" can be mentioned.
Preferable examples of the "lower alkylthio group" in the "lower alkylthio group optionally substituted with one or more halogen atoms" which is a substituent of E include methylthio, ethylthio, n-propylthio, isopropylthio, n- butylthio, isobutylthio, sec-butylthio, tert-butylthio, n- pentylthio, sec-pentylthio, isopentylthio, neopentylthio, n-hexylthio, isohexylthio and the like, 'and
as the "halogen atom", the aforementioned "halogen atom" can be mentioned.
Preferable examples of the "lower alkylsulfinyl group" in the "lower alkylsulfinyl group optionally substituted with one or more halogen atoms" which is a substituent of E include methylsulfinyl, ethylsulfinyl, n-propylsulfinyl, isopropylsulflnyl, n-butylsulfinyl, isobutylsulfinyl, sec- butylsulfinyl, tert-butylsulfinyl, n-pentylsulfinyl, sec- pentylsulfinyl, isopentylsulfinyl, neopentylsulfinyl, n- hexylsulfinyl, isohexylsulfinyl and the like, and
as the "halogen atom", the aforementioned "halogen atom" can be mentioned.
Preferable examples of the "lower alkylsulfonyl group" in the "lower alkylsulfonyl group optionally substituted with one or more halogen atoms" which is a substituent of E include methylsulfonyl, ethylsulfonyl, n-propylsulfonyl, isopropylsulfonyl, n-butylsulfonyl, isobutylsulfonyl, sec- butylsulfonyl, tert-butylsulfonyl, n-pentylsulfonyl, sec- pentylsulfonyl, isopentylsulfonyl, neopentylsulfonyl, n- hexylsulfonyl, isohexylsulfonyl and the like, and
as the "halogen atom", the aforementioned "halogen atom" can be mentioned.
Preferable examples of the "aryl group" represented by E include phenyl, 1-naphthyl, 2-naphthyl, biphenylyl, 2- anthryl and the like.
Preferable examples of the "heterocyclic group" represented by E include an "aromatic monocyclic
heterocyclic group", and examples of the aromatic
monocyclic heterocyclic group include 5-membered aromatic monocyclic heterocyclic groups such as 2-furyl, 3-furyl, 2- thienyl, 3-thienyl, 2-pyrrolyl, 3-pyrrolyl, 2-oxazolyl, A- oxazolyl, 5-oxazolyl, 3-isoxazolyl, 4-isoxazolyl, 5- isoxazolyl, 2-thiazolyl, 4-thiazolyl, 5-thiazolyl, 3- isothiazolyl, 4-isothiazolyl, 5-isothiazolyl, 2-imidazolyl, 4-imidazolyl, 5-imidazolyl, 3-pyrazolyl, 4-pyrazolyl, 5- pyrazolyl, 1, 2, 3-oxadiazol-4-yl, 1, 2, 3-oxadiazol-5-yl, 1, 2, 4-oxadiazol-5-yl, 1, 2, 4-oxadiazol-3-yl, 1,3,4- oxadiazol-2-yl, furazanyl, 1, 2, 3-thiadiazol-4-yl, 1,2,3- thiadiazol-5-yl, 1, 2, 4-thiadiazol-3-yl, 1, 2, 4-thiadiazol-5- yl, 1, 3, 4-thiadiazol-2-yl, IH-I, 2, 3-triazol-4-yl, IH-I, 2,3- triazol-5-yl, IH-I, 2, 4-triazol-3-yl, lH-tetrazol-5-yl and the like, and
6-membered aromatic monocyclic heterocyclic groups such as 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyrimidinyl, A- pyrimidinyl, 5-pyrimidinyl, 3-pyridazinyl, 4-pyridazinyl, 2-pyrazinyl, 1, 2, 4-triazin-3-yl, 1, 2, 4-triazin-5-yl, 1,2,4- triazin-6-yl, 1, 3, 5-triazin-2-yl and the like.
Preferable examples of the "aryl group" in the "aryl group optionally substituted with one or more substituents" represented by Q include phenyl, mesityϊ, xylyl, tolyl, naphthyl, anthracenyl and the like, and
preferable examples of the "substituent" of the "one or more substituents" in the "aryl group optionally
substituted with one or more substituents" include a halogen atom (fluorine atom, chlorine atom, bromine atom, iodine atom) , nitro, cyano, lower alkyl substituted with a halogen atom (e.g. chloromethyl, difluoromethyl,
trichloromethyl, trifluoromethyl, 2-bromoethyl, 2,2,2- trifluoroethyl, pentafluoroethyl, 3, 3, 3-trifluoropropyl, 4, 4, 4-trifluorobutyl, 5, 5, 5-trifluoropentyl, 6,6,6- trifluorohexyl and the like), lower alkoxy (e.g. methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, pentyloxy. hexyloxy etc.) and the like.
Preferable examples of the "heterocyclic group" in the "heterocyclic group optionally substituted with one or more substituents" represented by Q include an "aromatic
monocyclic heterocyclic group", and examples of the
aromatic monocyclic heterocyclic group include 5-membered aromatic monocyclic heterocyclic group such as 2-furyl, 3- furyl, 2-thienyl, 3-thienyl, 2-pyrrolyl, 3-pyrrolyl, 2- oxazolyl, 4-oxazolyl, 5-oxazolyl, 3-isoxazolyl, 4- isoxazolyl, 5-isoxazolyl, 2-thiazolyl, 4-thiazolyl, 5- thiazolyl, 3-isothiazolyl, 4-isothiazolyl, 5-isothiazolyl, 2-imidazolyl, 4-imidazolyl, 5-imidazolyl, 3-pyrazolyl, 4- pyrazolyl, 5-pyrazolyl, 1, 2, 3-oxadiazolJ4-yl, 1,2,3- oxadiazol-5-yl, 1, 2, 4-oxadiazol-5-yl, 1, 2, 4-oxadiazol-3-yl, 1, 3, 4-oxadiazol-2-yl, furazanyl, 1, 2 , 3-thiadiazol-4-yl, 1,2, 3-thiadiazol-5-yl, 1, 2, 4-thiadiazol-3-yl, 1,2,4- thiadiazol-5-yl, 1, 3, 4-thiadiazol-2-yl, IH-I, 2, 3-triazol-4- yl, 1H-1,2, 3-triazol-5-yl, IH-I, 2, 4-triazol-3-yl, IH- tetrazol-5-yl and the like, and
β-membered aromatic monocyclic heterocyclic groups such as 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyrimidinyl, 4- pyrimidinyl, 5-pyrimidinyl, 3-pyridazinyl, 4-pyridazinyl, 2-pyrazinyl, 1, 2, 4-triazin-3-yl, 1, 2, 4-triazin-5-yl, 1,2,4- triazin-6-yl, 1, 3, 5-triazin-2-yl and the like, and
preferable examples of the "substituent" of the "one or more substituents" in the "heterocyclic group optionally substituted with one or more substituents" include a halogen atom (fluorine atom, chlorine atom, bromine atom, iodine atom) , nitro, cyano, lower alkyl optionally
substituted with a halogen atom (e.g. methyl, chlromethyl, difluoromethy, trichloromethyl, trifluoromethyl, ethyl, 2- bromoethyl, 2, 2, 2-trifluoroethyl, pentafluoroethyl, propyl, 3, 3, 3-trifluoropropyl, isopropyl, butyl, isobutyl, sec- butyl, tert-butyl, 4 , 4 , 4-trifluorobutyl, pentyl, isopentyl, neopentyl, 5, 5, 5-trifluoropentyl, hexyl, 6,6,6- trifluorohexyl etc.), lower alkoxy (e.g. methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, pentyloxy, hexyloxy etc.) and the like.
Examples of aspects of the compound (I) include:
"Aspect 1"
A compound in which, in the formula (I),
X and Y are an oxygen atom,
R1 is a hydrogen atom,
a lower alkyl group optionally substituted. with one or more substituents,
a lower alkenyl group optionally substituted with one or more substituents,
a lower alkynyl group optionally substituted with one or more substituents,
an aryl lower alkyl group optionally substituted with one or more substituents,
a lower alkoxy lower alkyl group optionally substituted with one or more substituents,
an aryloxy lower alkyl group optionally substituted with one or more substituents,
a lower alkylthio lower alkyl group optionally substituted with one or more substituents,
a lower alkylsulfinyl lower alkyl group optionally
substituted with one or more substituents,
a lower alkylsulfonyl lower alkyl group optionally
substituted with one or more substituents, a mono or di (lower alkyl) amino lower alkyl group optionally substituted with one or more substituents, or
a lower alkanoyl group optionally substituted with one or more substituents,
R2 is a methylene group, an ethylene group, or a trimethylene group,
A is a group represented by OR3
(wherein R3 is a C1-C3 alkyl group optionally substituted with one or more substituents,
a lower alkanoyl group optionally substituted with one or more substituents, or
an aryl lower alkyl group optionally substituted with one or more substituents) ,
a group represented by S(O)nR4
(wherein R4 is a C1-C3 alkyl group optionally substituted with one or more substituents, and
n is an integer of 0 to 2) , or
a group represented by NR5R6
(wherein R5 and R6 each are independently a C1-C3 alkyl group optionally substituted with one or more substituents, or
R5 and R6 are taken together at the ends thereof to form together with the nitrogen atom a 3- to 7-membered nitrogen containing heterocycle optionally having another nitrogen atom, an oxygen atom and a sulfur atom as a ring constituting atom) ,
R7 is a halogen atom,
a lower alkoxycarbonyl group optionally substituted with one or more halogen atoms,
a lower alkyl group optionally substituted with one or more halogen atoms;
a lower alkoxy group optionally substituted with one or more halogen atoms,
a lower alkoxy lower alkoxy group optionally substituted with one or more halogen atoms,
a lower alkylthio group optionally substituted with one or more^halogen atoms,
a lower alkenylthio group optionally substituted with one or more halogen atoms,
a lower alkynylthio group optionally substituted with one or more halogen atoms,
a lower alkylsulfinyl group optionally substituted with one or more halogen atoms,
a lower alkenylsulfinyl group optionally substituted with one or more halogen atoms,
a lower alkylsulfonyl group optionally substituted with one or more halogen atoms,
a lower alkenylsulfonyl group optionally substituted with one or more halogen atoms,
a lower alkoxy lower alkylthio group optionally substituted with one or more halogen atoms, or
a group represented by -G-E
(wherein G is an oxygen atom or a sulfur atom, and
E is an aryl group or a heterocyclic group optionally substituted with one or more substituents selected from the group consisting of (1) a halogen atom, and (2) a lower alkyl group optionally substituted with one or more halogen atoms) ,
Q is a 2, 6-difluorophenyl group, a 2-chloro-6- fluorophenyl group, a 2, 6-dichlorophenyl group, a 3- chloropyridin-2-yl group, or a 3, 5-dichloropyridin-4-yl group, and
m is an integer of 1 to 4 (provided that when m is an integer of 2 to 4, R7S may be the same or different) .
"Aspect 2"
A compound in which, in the formula (I),
X and Y are an oxygen atom,
R1 is a hydrogen atom,
a lower alkyl group optionally substituted with one or more substituents,
a lower alkenyl group optionally substituted with one or more substituents,
a lower alkynyl group optionally substituted with one or more substituents,
a lower alkoxy lower alkyl group optionally substituted with one or more substituents,
an aryloxy lower alkyl group optionally 'substituted with one or more substituents,
a lower alkylthio lower alkyl group optionally substituted with one or more substituents,
a lower alkylsulfonyl lower alkyl group optionally
substituted with one or more substituents, or
a lower alkanoyl group optionally substituted with one or more substituents,
R2 is a methylene group, an ethylene group, or a trimethylene group,
NA is a group represented by OR3
(wherein R3 is a C1-C3 alkyl group optionally substituted with one or more substituents,
a lower alkanoyl group optionally substituted with one or more substituents, or
an aryl lower alkyl group optionally substituted with one or more substituents) ,
a group represented by S(O)nR4
(wherein R4 is a C1-C3 alkyl group optionally substituted with one or more substituents, and
n is an integer of 0 to 2) , or
a group represented by NR5R6
(wherein R5 and R6 each are independently a C1-C3 alkyl group optionally substituted with one or more substituents, or
R5 and R6 are taken together at the 'ends thereof to form together with the nitrogen atom a 3- to 7-membered nitrogen-containing heterocycle optionally having another nitrogen atom, an oxygen atom and a sulfur atom as a ring constituting atom) ,
R7 is a halogen atom,
a lower alkoxycarbonyl group optionally substituted with one or more halogen atoms,
a lower alkyl group optionally substituted with one or more halogen atoms,
a low.er alkoxy group optionally substituted with one or more halogen atoms,
a lower alkoxy lower alkoxy group optionally substituted with one or more halogen atoms,
a lower alkylthio group optionally substituted with one or more halogen atoms,
a lower alkenylthio group optionally substituted with one or more halogen atoms,
a lower alkynylthio group optionally substituted with one or more halogen atoms,
a lower alkylsulfinyl group optionally substituted with one or more halogen atoms,
a lower alkenylsulfinyl group optionally substituted with one or more halogen atoms, a lower alkylsulfonyl group optionally substituted with one or more halogen atoms, '
a lower alkoxy lower alkylthio group optionally substituted with one, or more halogen atoms, or
a group represented by -G-E
(wherein G is" an oxygen atom or a sulfur atom, and
E is an aryl group or a heterocyclic group optionally substituted with one or more substituents selected from the group consisting of (1) a halogen atom, and (2) a lower alkyl group optionally substituted with one or more halogen atoms) ,
NιQ is a 2, 6-difluorophenyl group, a 2-chloro-6- fluorophenyl group, a 2 , 6-dichlorophenyl group, a 3- chloropyridin-2-yl group, or a 3, 5-dichloropyridin-4-yl group, and
m is an integer of 1 to 4 (provided that when m is an integer of 2 to 4, R7S may be the same or different) .
"Aspect 3"
A compound in which, in the formula (I),
X and Y are an oxygen atom,
R1 is a hydrogen atom, methyl, 2-propenyl, 2-propynyl, benzyl, methoxymethyl, ethoxymethyl, 2-phenoxyethyl, methylthiomethyl, 2-methylthioethyl, 2-methylsulfinylethyl, 2-methylsulfonylethyl, 2-dimethylaminoethyl, or acetyl,
R2 is a methylene group, an ethylene group, or a trimethylene group,
A is a group represented by OR3
(wherein R3 is methyl, ethyl, 2-chloroethyl, acetyl, or benzyl) , .
a group represented by S(O)nR4
(wherein R4 is methyl, and
n is a integer of 0 to 2) , or
a group represented by NR5R6
(wherein R5 and R6 are methyl, or
R5 and R6 are taken together at the ends thereof to form together with the nitrogen atom morpholino) ,
xιR7 is a fluorine atom, a chlorine atom, tert- butoxycarbonyl, trifluoromethyl, 1, 1, 2, 2-tetrafluoroethoxy, trifluoromethoxy, 1,1, 2-trifluoro-2-trifluoromethoxyethoxy, trifluromethylthio, difluoromethylthio, methylthio,
ethylthio, 1, 1, 2, 2-tetrafluoroethylthio, 2,2,2- trifluoroethylthio, 1,1,2,2, 2-pentafluoroethylthio,
1,1,2,2,3,3, 3-heptafluoro-1-propylthio, 1,1,2,3,3,3- hexafluoro-1-propylthio, 2-propynylthio, 3, 3-dichloro-2- propenylthio, 2-propynylthio, trifluoromethylsulfinyl, 1,1,2, 2-tetrafluoroethylsulfinyl, 2-propenylsulfinyl, trifluoromethylsulfonyl, 1,1,2, 2-tetrafluoroethylsulfonyl, 2-propenylsulfonyl, 1, 1, 2-trifluoro-2- trifluoromethoxyethylthio, or 3-chloro-5-trifluoromethyl-2- pyridylthio, 3-chloro-4-trifluoromethylphenoxy, or 3- chloro-5-trifluoromethyl-2-pyridyloxy,
Q is a 2, β-difluorophenyl group, a 2-chloro-6- N fluorophenyl group, a 2, 6-dichlorophenyl group, a 3- chloropyridin-2-yl group, or a 3, 5-dichloropyridin-4-yl group, and
m is an integer of 1 to 4 (provided that when m is an integer of 2 to 4, R7 ' s may be the same or different) .
"Aspect 4"
A compound in which, in the formula (I),
X and Y are an oxygen atom,
R1 is a hydrogen atom, methyl, 2-propenyl, 2-propynyl, benzyl, methoxymethyl, ethoxymethyl, 2-phenoxyethyl, methylthiomethyl, 2-methylthioethyl, 2-methylsulfonylethyl, or acetyl,
R2 is a methylene group, an ethylene group, or a trimethylene group,
A is a group represented by OR3
(wherein R3 is methyl, ethyl, 2-chloroethyl, acetyl, or benzyl) ,
a group represented by S(O)nR4
(wherein R4 is methyl, and
n is a integer of 0 to 2), or
a group represented by NR5R6
(wherein R5 and R6 are methyl, or
R5 and R6 are taken together at the ends thereof to form together with the nitrogen atom morpholino) ,
R is fluorine atom, a chlorine atom, tert- butoxycarbonyl, trifluoromethyl, 1, 1, 2, 2-tetrafluoroethoxy, trifluoromethoxy, 1, 1, 2-trifluoro-2-trifluoromethoxyethoxy, trifluromethylthio, difluoromethylthio, methylthio,
ethylthio, 1, 1, 2, 2-tetrafluoroethylthio, 2,2,2- trifluoroethylthio, 1,1,2,2, 2-pentafluoroethylthio,
1,1,2,2,3,3, 3-heptafluoro-l-propylthio, 1,1,2,3,3,3- hexafluoro-1-propylthio, 2-propenylthio, 3, 3-dichloro-2- propenylthio, 2-propynylthio, trifluoromethylsulfinyl, 1, 1,2, 2-tetrafluoroethylsulfinyl, 2-propenylsulfinyl, trifluoromethylsulfonyl, 1,1,2, 2-tetrafluoroethylsulfonyl, 1,1, 2-trifluoro-2-trifluoromethoxyethylthio, 3-chloro-5- trifluoromethyl-2-pyridylthio, 3-chloro-4- trifluoromethylphenoxy, or 3-chloro-5-trifluoromethyl-2- pyridyloxy,
Q is a 2, 6-difluorophenyl group, a 2-chloro-6- fluorophenyl group, a 2, 6-dichlorophenyl group, a 3- chloropyridin-2-yl group, or a 3, 5-dichloropyridin-4-yl group, and
m is an integer of 1 to 4 (provided that when m is an integer of 2 to 4, R7 ' s may be the same or different).
"Aspect 5"
The following compounds:
1- (2, 6-difluorobenzoyl) -3- [2-fluoro-4- (trifluoromethylthio) phenyl] -1, 3-bis (methoxymethyl) urea, 1- (2, β-difluorobenzoyl) -1, 3-bis (etHoxymethyl) -3- [2- fluoro-4- (trifluoromethylthio) phenyl] urea,
1- (2-chloro-β-fluorobenzoyl) -3- [2-fluoro-4- (trifluoromethylthio) phenyl] -1, 3-bis (methoxymethyl) urea,
1- (2, 6-dichlorobenzoyl) -3- [2-fluoro-4- (trifluoromethylthio) phenyl] -1, 3-bis (methoxymethyl) urea,
1- (2, 6-difluorobenzoyl) -3- [2-fluoro-4-
(trifluoromethylthio) phenyl] -1, 3-bis (methylthiomethyl) urea, 1- (4-chloro-2-fluorophenyl) -3- (2, 6-difluorobenzoyl) - 1, 3-bis (methoxymethyl) urea,
si- ( 4-chlorophenyl) -3- (2, 6-difluorobenzoyl) - 1, 3- bis (methoxymethyl ) urea,
1- (3, 5-dichloro-2, 4-difluorophenyl) -3- (2, 6- difluorobenzoyl) - 1, 3-bis (methoxymethyl) urea,
. 1- [4- (2-chloro-4-trifluoromethylphenoxy) -2- fluorophenyl] -3- (2, 6-difluorobenzoyl) -1, 3- bis (methoxymethyl) urea,
1- (2, 6-difluorobenzoyl) -3- [2-fluoro-4- (1, 1,2,2- tetrafluoroethylthio) phenyl] - 1, 3-bis (methoxymethyl) urea,
1- (2, 6-difluorobenzoyl) -3- (2-fluoro-4- methylthiophenyl) -1, 3-bis (methoxymethyl) urea,
1- (2-chloro-6-fluorobenzoyl) -3- (2-fluoro-4- methylthiophenyl) -1, 3-bis (methoxymethyl) urea,
1- (2, 6-difluorobenzoyl) -3- (2-fluoro-4- ethylthiophenyl) -1, 3-bis (methoxymethyl) urea,
1- (2, 6-difluorobenzoyl)-3-[2-fluord-4-(l, 1,2,2,2- pentafluoroethylthio) phenyl] -1, 3-bis (methoxymethyl) urea,
1- (2, 6-difluorobenzoyl) -3- [2-fluoro-4- (1,1,2,2,3,3,3- heptafluoro-1-propylthio) phenyl] -1, 3-bis (methoxymethyl) urea,
1- (2-chloro-β-fluorobenzoyl) -3- (2-fluoro-4- ethylthiophenyl) -1, 3-bis (methoxymethyl) urea,
1- (2, 6-difluorobenzoyl) -3- [2-fluoro-4- (1, 1,2,2- tetrafluoroethoxy) phenyl] -1, 3-bis (methoxymethyl) urea,
1- (2, 6-difluorobenzoyl) -3- (2-fluoro-4- trifluoromethylphenyl) -1, 3-bis (methoxymethyl) urea,
1- (2-chloro-6-fluorobenzoyl) -3- [2-fluoro-4- (1,1,2,2- tetrafluoroethylthio) phenyl] -1, 3-bis (methoxymethyl) urea,
1- (2, β-difluorobenzoyl) -1, 3-bis (methoxymethyl) -3- (4- trifluoromethoxyphenyl) urea,
1- (2, β-difluorobenzoyl) -3- [2-fluoro-4- (trifluoromethylthio) phenyl] -3- (methoxymethyl) -1-methylurea,
3- (2, 6-difluorobenzoyl) -1- (ethoxymethyl) -1- [2-fluoro- 4- (trifluoromethylthio) phenyl] urea,
3- (2, 6-difluorobenzoyl) -1- [2-fluoro-4-
(trifluoromethylthio) phenyl] -1- (methylthiomethyl) urea,
1- (4-chloro-2-fluorophenyl) -3- (2, 6-difluorobenzoyl) -1- (methoxymethyl) urea,
3- (2, 6-difluorobenzoyl) -1- [2-fluoro-4- (2-chloro-4- trifluoromethylphenoxy) phenyl] -1- (methoxymethyl) urea, 1- ( 4-chlorophenyl ) -3- (2, 6-difluorobenzoyl) -1- (methoxymethyl) urea,
3- (2, 6-difluorobenzoyl) -1- [2-fluoro-4- (1, 1, 2, 2, 2- pentafluoroethylthio) phenyl] -1- (methoxymethyl) urea, 1- (4-chlorophenyl) -3- (2, β-dichlorobenzoyl) -1- (ethoxymethyl) urea,
3- (2, 6-difluorobenzoyl) -1- [2-fluoro-4- (trifluoromethylthio) phenyl] -1- (methoxymethyl) urea,
3- (2, 6-dichlorobenzoyl) -1- [2-fluoro-4- (trifluoromethylthio) phenyl] -1- (methoxymethyl) urea,
3- (2-chloro-6-fluorobenzoyl) -1- [2-fluoro-4- (trifluoromethylthxo) phenyl] -1- (methoxymethyl) urea,
3- (2, 6-difluorobenzoyl) -1- [2-fluoro-4- (1, 1, 2, 2- tetrafluoroethylthio) phenyl] -1- (methoxymethyl) urea, 3- (2, 6-difluorobenzoyl) -1- (2-fluoro-4- methylthiophenyl) -1- (methoxymethyl) urea,
3- (2-chloro-6-fluorobenzoyl) -1- (2-fluoro-4- methylthiophenyl) -1- (methoxymethyl) urea,
3- (2, 6-difluorobenzoyl) -1- (2-fluoro-4- ethylthiophenyl) -1- (methoxymethyl) urea,
3- (2-chloro-6-fluorobenzoyl) -1- (2-fluoro-4- ethylthiophenyl) -1- (methoxymethyl) urea,
3- (2, 6-difluorobenzoyl )-l- [2-fluoro-4- (1, 1,2,2- tetrafluoroethoxy) phenyl] -1- (methoxymethyl) urea,
3- (2, 6-difluorobenzoyl) -1- (2-fluoro-4- trifluoromethylphenyl) -1- (methoxymethyl) urea,
3- (2-chloro-6-fluorobenzoyl) -1- [2-fluoro-4- (1,1,2,2- tetrafluoroethylthio) phenyl] -1- (methoxymethyl) urea,
3- (2, 6-difluorobenzoyl)-l-[2-fluoro-4- (1,1,2,2,3,3,3- heptafluoro-1-propylthio) phenyl] -1- (methoxymethyl) urea,
3- (2-chloro-β-fluorobenzoyl) -1- [2-fluoro-4- (1,1,2,2,3,3, 3-heptafluoro-1-propylthio) phenyl] -1- (methoxymethyl) urea,
3- (2, β-difluorobenzoyl) -1- [2-fluoro-4- (trifluoromethylsulfinyl) phenyl] -1- (methoxymethyl) urea,
3- (2, 6-difluorobenzoyl)-l-[2-fluoro-4- (1,1,2,2- tetrafluoroethylsulfonyl) phenyl] -1- (methoxymethyl) urea,
1- (2, 6-difluorobenzoyl) -3- [2-fluoro-4-
(trifluoromethylsulfinyl) phenyl] -1, 3-bis (methoxymethyl) urea, l-(2, 6-difluorobenzoyl) -3- [2-fluoro-4- (1,1,2,2- tetrafluoroethylsulfinyl) phenyl] -1, 3-bis (methoxymethyl) urea,
3- (2, 6-difluorobenzoyl) -1- [2-fluoro-4- (trifluoromethylsulfonyl) phenyl] -1- (methoxymethyl) urea,
3- (2, 6-difluorobenzoyl) -1- [2-fluoro-4- ( 1, 1, 2, 2- tetrafluoroethylsulfonyl) phenyl] -1- (methoxymethyl) urea,
1- (2, 6-difluorobenzoyl) -3- [2-fluoro-4- (trifluoromethylsulfonyl) phenyl] -1, 3-bis (methoxymethyl) urea, l-(2, 6-difluorobenzoyl) -3- [2-fluoro-4- (1, 1,2,2- tetrafluoroethylsulfonyl) phenyl] -1, 3-bis (methoxymethyl) urea, 1- (2, 6-difluorobenzoyl) -1, 3-bis (methoxymethyl) -3- (4- trifluoromethylthiophenyl) urea,
1- (2-chloro-4-trifluoromethylthiophenyl) -3- (2, 6- difluorobenzoyl) -1, 3-bis (methoxymethyl) urea,
1- [4- ( 3-chloro-5-trifluoromethyl-2-pyridylthio) -2- fluorophenyl] -3- (2, 6-difluorobenzoyl) -1, 3- bis (methoxymethl) urea,
1- [4- (3-chloro-5-trifluoromethyl-2-pyridyloxy) -3, 5- dichlorophenyl] -3- (2, 6-difluorobenzoyl) -1, 3- bis (methoxymethyl) urea,
1- (2, 6-difluorobenzoyl) -1, 3-bis (methoxymethyl) -3- [2- methyl-4- (trifluoromethylthio) phenyl] urea,
^1I- (2, 6-difluorobenzoyl) -3- [2, 3-dimethyl-4- (trifluoromethylthio) phenyl] -1, 3-bis (methoxymethyl) urea,
1- (2, 6-difluorobenzoyl) -3- [2-fluoro-4- (t- butoxycarbonyl) phenyl] -1, 3-bis (methoxymethyl) urea,
. 1- (3-chloropyridin-2-ylcarbonyl ) -3- [2-fluoro-4- (trifluoromethylthio) phenyl] -1, 3-bis (methoxymethyl) urea, 1- (3, 5-dichloropyridin-4-ylcarbonyl) -3- [2-fluoro-4- (trifluoromethylthio) phenyl] -1, 3-bis (methoxymethyl) urea, 1- (2, 6-difluorobenzoyl) -3- (4-difluoromethylthio-2- fluorophenyl) -1, 3-bis (methoxymethyl) urea,
1- (2-chloro-6-fluorobenzoyl) -3- (4-difluoromethylthio- 2-fluorophenyl) -1, 3-bis (methoxymethyl) urea,
l-(2, 6-difluorobenzoyl) -3- [2-fluoro-4- (1, 1,2,3,3,3- hexafluoro-1-propylthio) phenyl] -1, 3-bis (methoxymethyl) urea, 1- (2, 6-difluorobenzoyl) -3- [2-fluoro-4- (1,1,2,2,3,3,3- heptafluoro-1-pyopylthio) phenyl] -1, 3-bis (methoxymethyl) urea,
1- (2, 6-difluorobenzoyl) -3- [2-fluoro-4- (2,2,2- trifluorpethylthio) phenyl] -1, 3-bis (methoxymethyl) urea,
1- [2-chloro-4- (difluoromethylthio) phenyl] -3- (2, 6- difluorobenzoyl) -1, 3-bis (methoxymethyl) urea,
3- (2, 6-difluorobenzoyl) -1- [2-fluoro-4- (difluoromethylthio) phenyl] -1-methoxymethylurea,
3- (2, 6-difluorobenzoyl) -1- [2-fluoro-4- (2,2,2- trifluoroethylthio) phenyl] -1-methoxymethylurea,
3- (2, 6-difluorobenzoyl) -1- [2-fluoro-4- (1,1,2,3,3, 3- hexafluoro-1-propylthio) phenyl] -1-methoxymethylurea,
3- (2, 6-difluorobenzoyl) -1- [2-fluoro-4- (trifluoromethylthio) phenyl] -1- (2-methoxyethyl) urea,
l-acetyl-3- (2-acetoxyethyl) -1- (2, 6-difluorobenzoyl) -3- [2-fluoro-4- (trifluoromethylthio) phenyl] urea,
l-benzyloxymethyl-3- (2, 6-difluorobenzoyl) -1- [2-fluoro- 4- (trifluoromethylthio) phenyl] -3-methylurea,
1- (2-chloroethoxymethyl) -3- (2, 6-difluorobenzoyl) -1- [2- fluoro-4- (trifluoromethylthio) phenyl] -3-methylurea,
1- (2-acetoxyethyl) -3- (2, 6-difluorobenzoyl) -1- [2- fluoro-4- (trifluoromethylthio) phenyl] -3-methylurea,
1-allyl-l- (2, 6-difluorobenzoyl) -3- [2-fluoro-4- (trifluoromethylthio) phenyl] -3-methoxymethylurea,
1- (2, 6-difluorobenzoyl) -3- [2-fluoro-4- (trifluoromethylthio) phenyl] -3-methoxymethyl-l- propargylurea,
1- (2, 6-difluorobenzoyl) -3- [2-fluoro-4- (trifluoromethylthio) phenyl] -3-methoxymethyl-l- (2- phenoxyethyl) urea,
1- (2, β-difluorobenzoyl) -3- [2-fluoro-4- (trifluoromethylthio) phenyl] -3-methoxymethyl-l- (2- methylthioethyl) urea,
1- (2, β-difluorobenzoyl) -3- [2-fluoro-4- (trifluoromethylthio) phenyl] -3-methoxymethyl-l- (2- methylsulfonylethyl) urea,
^l- (2, β-difluorobenzoyl) -3- [2-fluoro-4- (trifluoromethylthio) phenyl] -3-methoxymethyl-l-propyl urea,
1-benzyl-l- (2, 6-difluorobenzoyl) -3- [2-fluoro-4- (trifluoromethylthio) phenyl] -3-methoxymethylurea,
. 1- (2, β-difluorobenzoyl) -3- [2, 5-difluoro-4- (trifluoromethylthio) phenyl] -1, 3-bis (methoxymethyl) urea,
1- (2, 6-difluorobenzoyl) -3- [2, 6-difluoro-4- ( trifluoromethylthio) phenyl] -1, 3-bis (methoxymethyl) urea, 1- (2, 6-difluorobenzoyl) -3- [2-fluoro-4- (2- propenylthio) phenyl] -1, 3-bis (methoxymethyl) urea,
1- (2, 6-difluorobenzoyl) -3- [2-fluoro-4- (2- propenylsulfinyl) phenyl] -1, 3-bis (methoxymethyl) urea,
1- (2, 6-difluorobenzoyl) -3- [2-fluoro-4- (2- propynylthio) phenyl] -1, 3-bis (methoxymethyl) urea, no
1- [4- (3, 3-dichloro-2-propenylthio) -2-fluorophenyl] -3- (2, β-difluorobenzoyl) -1, 3-bis (methoxymethyl) urea,
1- [2-chloro-4- (pentafluoroethylthio) phenyl] -3- (2,6- difluorobenzoyl) -1, 3-bis (methoxymethyl) urea,
1- (2, 6-difluorobenzoyl) -3- [2-fluoro-4- ( 1, 1,2- trifluoro-2-trifluoromethoxyethylthio) phenyl] -1, 3- bis (methoxymethyl) urea,
1- [3-chloro-4- (1, 1, 2-trifluoro-2- trifluoromethoxyethoxy) phenyl] -3- (2, 6-difluorobenzoyl ) -1, 3- bis (methoxymethyl) urea,
1-acetyl-l- (2, 6-difluorobenzoyl) -3- [2-fluoro-4- (trifluoromethylthio) phenyl] -3-methoxymethylurea,
1- (2, 6-difluorobenzoyl) -3- [2-fluoro-4- (trifluoromethylthio) phenyl] -l-methyl-3- [3- (methylsulfinyl) propyl] urea,
- 1- (2, 6-difluorobenzoyl) -3- [2-fluoro-4- (trifluoromethylthio) phenyl] -l-methyl-3- [3- (methylsulfonyl) propyl] urea,
1- (2, 6-difluorobenzoyl) -3- [2-fluoro-4- (trifluoromethylthio) phenyl] -l-methyl-3- (3- morpholinopropyl) urea, and
1- (2, 6-difluorobenzoyl) -3- ( 3-dimethylaminopropyl) -3- [2-fluoro-4- (trifluoromethylthio) phenyl] -1-methylurea .
"Aspect 6"
A benzoyl urea compound represented by the formula (I- 100 ) :
Figure imgf000112_0001
wherein
R 100 represents a halogen atom,
R 200 represents a halogen atom,
R 1-100 represents a hydrogen atom, a C1-C4 al kyl group or a
Cl -C4al koxy C1-C4 al kyl group ,
R2"100 represents a C1-C4 al koxy group ,
R 7-100 \ represents a hydrogen atom or halogen atom, and
R7"200 represents a halogen atom, a C1-C4 alkoxy group optionally substituted with one or more halogen atoms, a C1-C4 alkylthio group optionally substituted with one or more halogen atoms, a C1-C4 alkylsulfinyl group optionally- substituted with one or more halogen atoms, or a C1-C4 alkylsulfonyl group optionally substituted with one or more halogen atoms.
"Aspect 7"
A compound in which, in the formula (1-100),
R 100 is a fluorine atom or a chlorine atom,
R 200 is a fluorine atom or a chlorine atom,
R 1-100 is a hydrogen atom, a C1-C4 alkyl group or a C1-C4 alkoxy C1-C4 alkyl group, R2"100 is a C1-C4 alkoxy group,
R 7-ioo ^3 a hydrOgen atom, a fluorine atom or a chlorine atom, and
R 7-2θo ^3 a halogen atom, a C1-C4 alkoxy group optionally substituted with one or more halogen atoms, a C1-C4 alkylthio group optionally substituted with one or more halogen atoms, a C1-C4 alkylsulfinyl group optionally substituted with one or more halogen atoms/ or a C1-C4 alkylsulfonyl group optionally substituted with one or more halogen atoms.
"Aspect 8"
\A compound in which, in the formula (1-100),
R100 is a halogen atom,
R200 is a halogen atom,
βi-ioo ^3 a methoxymethyl group,
R2"100 is a methoxy group, '
R7"100 is a hydrogen atom, a fluorine atom or a chlorine atom, and
R7"200 is a halogen atom, a C1-C4 alkoxy group optionally substituted with one or more halogen atoms, a C1-C4 alkylthio group optionally substituted with one or more halogen atoms, a C1-C4 alkylsulfinyl group optionally substituted with one or more halogen atoms, or a C1-C4 alkylsulfonyl group optionally substituted with one or more halogen atoms. "Aspect 9"
A compound in which, in the formula1 (1-100),
R100 is a halogen atom,
R200 is a halogen atom,
Ri-ioo is a methoxymethyl group,
R2"100 is a methoxy group,
R7-ioo is a f]_uorj_ne atom, and
R7"200 is a halogen atom, a C1-C4 alkoxy group optionally substituted with one or more halogen atoms, a C1-C4
alkylthio group optionally substituted with one or more halogen atoms, a C1-C4 alkylsulfinyl group optionally substituted with one or more halogen atoms, or a C1-C4 alkylsulfonyl group optionally substituted with one or more halogen atoms.
"Aspect 10"
. A compound in which-, in the formula (1-100),
R100 is a fluorine atom, or a chlorine atom,
R200 is a fluorine atom or a chlorine atom,
R i-ioo is a hydrOgen atom, a C1-C4 alkyl group or a C1-C4 alkoxy C1-C4 alkyl group,
R2"100 is a C1-C4 alkoxy group,
R7"100 is a hydrogen atom, a fluorine atom or a chlorine atom, and
R 7-2oo is a C1_C4 alkylthio group optionally substituted with one or more halogen atoms. "Aspect 11 "
A compound in which, in the formula1 (1-100) ,
R100 is a fluorine atom or a chlorine atom,
R200 is a fluorine atom or a chlorine atom,
Ri-ioo is a hydrogen atom, a C1-C4 alkyl group or a C1-C4 alkoxy C1-C4 alkyl group,
R2"100 is a C1-C4 alkoxy group,
R7"100 is a hydrogen atom, a fluorine atom or a chlorine atom, and
R7-20O ^3 a trifluoromethylthio group.
"Aspect 12"
\A compound in which, in the formula (1-100),
R100 is a fluorine atom or a chlorine atom,
R200 is a fluorine atom or a chlorine atom,
Ri-ioo is a hydrogen atom, a C1-C4 alkyl group or a C1-C4 alkoxy C1-C4 alkyl group>
R2-ioo is a C1_C4 alkoxy group,
R7-ioo ^5 a f]_uorj_ne atom, and
R 7-2oo j^s a trifluoromethylthio group.
Specific examples of the compounds of the present invention are as follows.
A compound represented by the formula (I-A) :
Figure imgf000115_0001
X1, Y1, R1, R2"1, R7"1 and R7"2 in the formula represent any of combinations described in "Table 1" to "Table 19".
Hereinafter, a methyl group is referred to as Me in some cases.
Table 1
Figure imgf000117_0001
Table 2
Figure imgf000118_0001
Table 3
Figure imgf000119_0001
Figure imgf000120_0001
Table 5
Figure imgf000121_0001
Table 6
Figure imgf000122_0001
Table 7
Figure imgf000123_0001
Table 8
Figure imgf000124_0001
Figure imgf000125_0001
Table 10
Figure imgf000126_0001
Table 11
Figure imgf000127_0001
Table 12
Figure imgf000128_0001
Figure imgf000129_0001
Table 14
Figure imgf000130_0001
Table 15
Figure imgf000131_0001
Table 16
Figure imgf000132_0001
Figure imgf000133_0001
Table 18
Figure imgf000134_0001
Table 19
Figure imgf000135_0001
Then, a process for producing the compound (I) will be explained.
The compound (I) can be produced, for example, by the following Process 1 to Process 10.
Process 1
Among the compounds (I), a compound represented by the formula (1-1) :
Figure imgf000136_0001
wherein R7, Q and m are as defined above,
X is an oxygen atom, Y is an oxygen atom, and
R11 is a Tower alkoxy lower alkyl group optionally substituted with one or more substituents, a lower
alkylthio lower alkyl group optionally substituted. with one or more substituents, a lower alkylsulfinyl lower alkyl group optionally substituted with one or more substituents, a lower alkylsulfonyl lower alkyl group optionally
substituted with one or more substituents, or a mono or di (lower alkyl) amino lower alkyl group optionally
substituted with one or more substituents,
can be produced by reacting a compound represented by the formula ( II ) :
Figure imgf000136_0002
wherein R7, Q and m are as defined above, and
X is an oxygen atom, and Y is an oxygen atom,
with a compound represented by the formula (III) :
Figure imgf000136_0003
wherein R11 is as defined above, and
L1 is a halogen atom (chlorine atom, bromine atom, and iodine atom) , a methanesulfonyloxy group, a
benzenesulfonyloxy group, or a toluenesulfonyloxy group.
The reaction is usually performed in a solvent in the presence of a base.
Examples of the solvent used in the reaction include ketones such as acetone, methyl ethyl ketone and the like, aromatic hydrocarbons such as benzene, toluene, xylene and the like, aliphatic hydrocarbons such as hexane, heptane and the like, ethers such as diethyl ether, tetrahydrofuran, 1,4-dioxane, 1, 2-dimethoxyethane, 1, 2-diethoxyethane and the like, halogenated hydrocarbons such as chloroform, chlorobenzene, dichlorobenzene and the like, nitriles such as acetonitrile and the like, aprotic polar solvents such as N, N-dimethylformamide, N, N-dimethylacetamide, 1-methyl- 2-pyrrolidone, 1, 3-dimethylimidazolinone, dimethyl
sulfoxide and the like, water, and a mixture thereof.
Examples of the base used in the reaction include hydroxides of an alkali metal or an alkaline earth metal such as sodium hydroxide, potassium hydroxide, calcium hydroxide and the like, hydrides of an alkali metal or an alkaline earth metal such as sodium hydride, potassium hydride, calcium hydride and the like, carbonates of an alkali metal or an alkaline earth metal such as sodium carbonate, potassium carbonate and the like, alcoholates of an alkali metal such as sodium ethylate, sodium methylate and the like, organic lithium such as normalbutyllithium, lithium diisopropylamide and the like, and organic bases such as triethylamine, pyridine, 1,8- diazabicyclo [5, 4, 0] undec-7-ene and the like.
Each reagent may be used in an excess amount in the reaction, when the reagent is liquid under reaction conditions. However, usually, the compound represented by the formula (III) is used at a proportion of 2 to 4 moles, and the base is used at a proportion of 2 to 4 moles based on 1 mole of the compound represented by the formula (II) .
The reaction temperature is usually in a range of -78 to 150°C, and the reaction time is usually in a range of 0.1 to 100 hours.
After completion of the reaction, the compound represented by the formula (1-1) can be isolated by performing a post-treatment procedure such as by pouring the reaction mixture into water, extracting this with an organic solvent, and drying and concentrating the organic layer. The isolated compound represented by the formula (1-1) can be further purified by recrystallization, column chromatography or the like.
The compound represented by the formula (II) can be produced by the process described in J. Agr. Food Chem. , Vol.21, No. 3, p.348-354 (1973), or modification thereof. Process 2 Among the compounds (I) , a compound represented by the formula (1-2) :
Figure imgf000139_0001
wherein R2, A," R7' Q and m are as defined above, and
X is an oxygen atom, Y is an oxygen atom,
R1"1 is a formyl group, a cyano group,■
a lower alkylsulfonyl group optionally substituted with one or more substituents,
an arylsulfonyl group optionally substituted with one or more^substituents,
a lower alkylcarbonylthio group optionally substituted with one or more substituents,
a lower alkoxycarbonylthio group optionally substituted with one or more substituents,
an aryloxycarbonylthio group optionally substituted with one or more substituents,
a mono or di (lower alkyl) aminosulfonyl group optionally substituted with one or more substituents,
a mono- or di- (aryl) aminosulfonyl group optionally
substituted with one or more substituents,
a lower alkyl group optionally substituted with one or more substituents,
a lower alkenyl group optionally substituted with one or more substituents,
a lower alkynyl group optionally substituted with one or more substituents,
a lower cycloalkyl group optionally substituted with one or more substituents,
an aryl lower" alkyl group optionally substituted with one or more substituents,
a lower alkoxy lower alkyl group optionally substituted with one or more substituents,
an aryloxy lower alkyl group optionally substituted with one or more substituents,
a lower alkylthio lower alkyl group optionally substituted with one or more substituents,
a lower alkylsulfinyl lower alkyl group optionally
substituted with one or more substituents,
a lower alkylsulfonyl lower alkyl group optionally
substituted with one or more substituents,
a mono or di (lower alkyl) amino lower alkyl group optionally substituted with one or more substituents,
a lower alkanoyl group optionally substituted with one or more substituents,
a lower alkoxy carbonyl group optionally substituted with one or more substituents,
an aryloxycarbonyl group optionally substituted with one or more substituents, an aryl (lower) alkoxycarbonyl group optionally substituted with one or more substituents,
a carbamoyl group optionally substituted with one or more substituents,
a thiocarbamoyl group optionally substituted with one or more substituents,
a lower alkoxyoxalyl group optionally substituted with one or more substituents,
an aryl lower alkoxyoxalyl group optionally substituted with one or more substituents,
an aryloxyoxalyl group optionally substituted with one or
Figure imgf000141_0001
an aminooxalyl group optionally substituted with one or more substituents,
can be produced by reacting a compound represented by the formula (IV) :
Figure imgf000141_0002
wherein R1 1, R7, Q and m are as defined above, and
X is an oxygen atom, and Y is an oxygen atom,
with a compound represented by the formula (V) :
A—R2—L2 ( V )
wherein A and R2 are as defined above, and
L2 is a halogen atom (chlorine atom, bromine atom, and iodine atom) , a methanesulfonyloxy group, a
benzenesulfonyloxy group, or a toluenesulfonyloxy group.
The reaction is usually performed in a solvent in the presence of a base.
Examples of the solvent used in the reaction include ketones such as acetone, methyl ethyl ketone and the like, aromatic hydrocarbons such as benzene, toluene, xylene and the like, aliphatic hydrocarbons such as hexane, heptane and the like, ethers such as diethyl ether, tetrahydrofuran, 1,4-dioxane, 1, 2-dimethoxyethane, 1, 2-diethoxyethane and the like, halogenated hydrocarbons such as chloroform, chlorobenzene, dichlorobenzene and the like, nitriles such as acetonitrile and the like, aprotic polar solvents such as N, N-dimethylformamide, N, N-dimethylacetamide, 1-methyl- 2-pyrrolidone, 1, 3-dimethylimidazolinone, dimethyl
sulfoxide and the like, water, and a mixture of thereof.
Examples of the base used in the reaction include hydroxides of an alkali metal or an alkaline earth metal such as sodium hydroxide, potassium hydroxide, calcium hydroxide and the like, hydrides of an alkali metal or an alkaline earth metal such as sodium hydride, potassium hydride, calcium hydride and the like, carbonates of an alkali metal or an alkaline earth metal such as sodium carbonate, potassium carbonate and the like, alcoholates of an alkali metal such as sodium ethylate, sodium methylate and the like, organic lithium such as normalbutyllithium, lithium diisopropylamide and the like, and organic bases such as triethylamine, pyridine, 1,8- diazabicyclo [5, 4 , 0] undec-7-ene and the like.
Each reagent may be used in an excess amount in the reaction, when the reagent is liquid under reaction conditions. However, usually, the compound represented by the formula (V) is used at a proportion of 1 to 3 moles, and the base is used at a proportion of 1 to 3 moles based on 1 mole of the compound represented by the formula (IV) .
The reaction temperature is usually in a range of -78 to 150°C, and the reaction time is usually in a range of 0.1 to 100 hours.
After completion of the reaction, the compound represented by the formula (1-2) can be isolated by performing a post-treatment procedure such as by pouring the reaction mixture into water, extracting this with an organic solvent, and drying and concentrating the organic layer. The isolated compound represented by the formula (1-2) can be further purified by recrystallization, column chromatography or the like.
The compound represented by the formula (IV) can be produced by the process described in J. Agr. Food Chem. , Vol.21, No. 3, p.348-354 (1973), or modification thereof. Process 3 Among the compounds (I), a compound represented by the formula (1-3) :
Figure imgf000144_0001
e as defined above, and
X is an oxygen atom, and Y is an oxygen atom,
can be produced by subjecting a compound of the formula (VI) :
Figure imgf000144_0002
wherein R2, R7, A, Q and m are as defined above, and
X is an oxygen atom, Y is an oxygen atom, and
J is a protecting group such as a 2- (trimethylsilyl) ethoxy methyl group, etc.,
to a deprotecting reaction. For example, when J is a 2- (trimethylsilyl) ethoxy methyl group, the production is performed by reacting the compound represented by the formula (VI) and a fluoride salt.
The reaction is usually performed in a solvent.
Examples of the solvent used in the reaction include ketones such as acetone, methyl ethyl ketone and the like, aromatic hydrocarbons such as benzene, toluene, xylene and the like, aliphatic hydrocarbons such as hexane, heptane and the like, ethers such as diethyl ether, tetrahydrofuran, 1,4-dioxane, 1, 2-dimethoxyethane, 1, 2-diethoxyethane and the like, halogenated hydrocarbons such as chloroform, chlorobenzene, dichlorobenzene and the like, nitriles such as acetonitrile and the like, aprotic polar solvents such as N, N-dimethylformamide, N, N-dimethylacetamide, 1-methyl- 2-pyrrolidone, 1, 3-dimethylimidazolinone, dimethyl
sulfoxide and the like, water, and a mixture thereof.
Examples of the fluoride salt used in the reaction include ammonium salts such as tetranormalbutylammonium fluoride and the like, and inorganic salts such as cesium fluoride and the like.
The amount of a fluoride salt used in the reaction is usually at a proportion of 1 to 10 moles based on 1 mole of the compound represented by the formula (VI).
■ The reaction temperature is usually in a range of -78 to 15O0C, and the reaction time is usually in a range of 0.1 to 100 hours.
After completion of the reaction, a compound
represented by the formula (1-3) can be isolated by
performing a post-treatment procedure such as by pouring the reaction mixture into water, extracting this with an organic solvent, and drying and concentrating the organic layer. The isolated compound represented by the formula (1-3) can be further purified by recrystallization, column chromatography or the like.
The compound (VI) can be produced bly the process described in Process 2.
Process 4
In addition, among the compounds (I), a compound represented by the formula (1-3) can be produced by
reacting a compound represented by the formula (VII):
Figure imgf000146_0001
wherein X, Y, and Q are as defined above,
with a compound represented by a formula (VIII) :
Figure imgf000146_0002
wherein A, R2, R7 and m are as defined above.
The reaction is usually performed in a solvent.
Examples of the solvent used in the reaction include ketones such as acetone, methyl ethyl ketone and the like, aromatic hydrocarbons such as benzene, toluene, xylene and the like, aliphatic hydrocarbons such as hexane, heptane and the like, ethers such as diethyl ether, tetrahydrofuran, 1,4-dioxane, 1, 2-dimethoxyethane, 1, 2-diethoxyethane and the like, halogenated hydrocarbons such as chloroform, chlorobenzene, dichlorobenzene and the like, nitriles such as acetonitrile and the like, aprotic polar solvents such as N,N-dimethylformamide, N, N-dimethylacetamide, 1-methyl- 2-pyrrolidone, 1, 3-dimethylimidazolinone, dimethyl
sulfoxide and the like, water, and a mixture thereof.
The - compound represented by the formula (VIII) is usually used in the reaction at a proportion of 0.5 to 2 moles based oh 1 mole of the compound represented by the formula (VIII) .
The reaction temperature is usually in a range of -78 to 150°C, and the reaction time is usually in a range of 0.1 to 100 hours.
After completion of the reaction, the compound
represented by the formula (1-3) can be isolated by
performing a post-treatment procedure such as by
concentrating or filtering the reaction mixture. The isolated compound represented by the formula (1-3) can be further purified by recrystallization, column
chromatography or the like.
The compound represented by the formula (VII) can be produced by the process described in J. Agr. Food Chem. , Vol.21, No. 3, p.348-354 (1973), or modification thereof.
In addition, the compound represented by the formula (VIII) can be produced by the process described in Journal of the Chemical Society Perkin Transactions 1 (1988) P1631-1636, or modification thereof.
Process 5 Among the compounds (I), a compound represented by the formula (1-4) :
Figure imgf000148_0001
wherein Y, R2,' R7, A, Q and m are as defined above, and
R1"2 is a lower alkyl group optionally substituted with one or more substituents,
a lower alkenyl group optionally substituted with one or more substituents,
a lower alkynyl group optionally substituted with one or more' substituents,
a lower cycloalkyl group optionally substituted with one or more substituents,
an aryl lower alkyl group optionally substituted with one or more substituents,
an aryl group optionally substituted with one or more substituents,
a lower alkoxy lower alkyl group optionally substituted with one or more substituents,
an aryloxy lower alkyl group optionally substituted with one or more substituents,
a lower alkylthio lower alkyl group optionally substituted with one or more substituents,
a lower alkylsulfinyl lower alkyl group optionally substituted with one or more substituents,
a lower alkylsulfonyl lower alkyl group 'optionally
substituted with one or more substituents,
a mono or di (lower alkyl) amino lower alkyl group optionally substituted with one or more substituents,
a lower alkoxy group optionally substituted with one or more substituents,
an aryloxy group optionally substituted with one or more substituents,
an aryl lower alkoxy group optionally substituted with one or more substituents,
an amino group optionally substituted with one or more substituents, or
a heterocyclic group optionally substituted with one or more substituents,
can be produced by reacting a compound represented by the formula (IX) :
Figure imgf000149_0001
wherein Y, Q and R1 2 are as defined above,
with a compound represented by the formula (VIII).
The reaction is usually performed in a solvent in the presence of a base.
Examples of the solvent used in the reaction include ketones such as acetone, methyl ethyl ketone and the like, aromatic hydrocarbons such as benzene, toluene, xylene and the like, aliphatic hydrocarbons such as hexane, heptane and the like, ethers such as diethyl ether, tetrahydrofuran, 1,4-dioxane, 1, 2-dimethoxyethane, 1, 2-diethoxyethane and the like, halogenated hydrocarbons such as chloroform, chlorobenzene, dichlorobenzene and the like, nitriles such as acetonitrile and the like, aprotic polar solvents such as N, N-dimethylformamide, N, N-dimethylacetamide, 1-methyl- 2-pyrrolidone, 1, 3-dimethylimidazolinone, dimethyl
sulfoxide and the like, water, and a mixture thereof.
^Examples of the base used in the reaction include hydroxides of an alkali metal or an alkaline earth metal such as sodium hydroxide, potassium hydroxide, calcium hydroxide and the like, hydrides of an alkali metal or an alkaline earth metal such as sodium hydride, potassium hydride, calcium hydride and the like, carbonates of an alkali metal or an alkaline earth metal such as sodium carbonate, potassium carbonate and the like, alcoholates of an alkali metal such as sodium ethylate, sodium methylate and the like, organic lithium such as normalbutyllithium, lithium diisopropylamide and the like, and organic bases such as triethylamine, pyridine, 1,8- diazabicyclo [5.4.0] undec-7-ene and the like.
Each reagent may be used in an excess amount in the reaction, when the reagent is liquid under reaction
conditions. However, usually, the compound represented by the formula (VIII) is used at a proportion of 1 to 4 moles, and the base is used at a proportion of 1 to 4 moles based on 1 mole of the compound represented by formula (IX) .
The reaction temperature is usually in a range of -78 to 15O0C, and the reaction time is usually in a range of 0.1 to 200 hours.
After completion of the reaction, the compound
represented by the formula (1-4) can be isolated by
performing a post-treatment procedure such as by pouring the reaction mixture into water, extracting this with an organic solvent, and drying and concentrating the organic layer. The isolated compound represented by the formula (1-4) can be further purified by recrystallization, column chromatography or the like.
Process 6
Among the compounds (I), a compound represented by the formula (1-5) :
Figure imgf000151_0001
wherein R2, R7, A, Q and m are as defined above,
X is an oxygen atom, Y is an oxygen atom, and
R1"3 is a formyl group, a cyano group,
a lower alkylsulfonyl group optionally substituted with one or more substituents,
an arylsulfonyl group optionally substituted with one or more substituents,
a lower alkylcarbonylthio group optionally substituted with one or more substituents,
a lower alkoxycarbonylthio group optionally substituted with one or more substituents,
an aryloxycarbonylthio group optionally substituted with one or more substituents,
a mono or di (lower alkyl) aminosulfonyl group optionally substituted with one or more substituents,
a mono- or di (aryl) aminosulfonyl group optionally
substituted with one or more substituents,
a lower alkyl group optionally substituted with one or more substituents,
a lower alkenyl group optionally substituted with one or more substituents,
a lower alkynyl group optionally substituted with one or more substituents,
a lower cycloalkyl group optionally substituted with one or more substituents,
an aryl lower alkyl group optionally substituted with one or more substituents, a lower alkoxy lower alkyl group optionally substituted with one or more substituents,
an aryloxy lower alkyl group optionally substituted with one or more substituents,
a lower alkylthio lower alkyl group optionally substituted with one or more substituents,
a lower alkylsulfinyl lower alkyl group optionally
substituted with one or more substituents,
a lower alkylsulfonyl lower alkyl group optionally
substituted with one or more substituents,
a mono or di (lower alkyl) amino lower alkyl group optionally substituted with one or more substituents,
a lower alkanoyl group optionally substituted with one or more substituents,
a lower alkoxycarbonyl group optionally substituted with one or more substituents,
an aryloxycarbonyl group optionally substituted with one or more substituents,
an aryl lower alkoxycarbonyl group optionally substituted with one or more substituents,
a carbamoyl group optionally substituted with one or more substituents,
a thiocarbamoyl group optionally substituted with one or more substituents,
a lower alkoxyoxalyl group optionally substituted with one or more substituents,
an aryl lower alkoxyoxalyl group optionally substituted with one or more substituents,
an -arylox-yoxalyl group optionally substituted with one or more substituents, or
an aminooxalyT group optionally substituted with one or more substituents,
can be produced by reacting a compound represented by the formula (1-3) and a compound represented by the formula (X) :
R1-3 L3 (X)
wherein R1"3 is as defined above, and
L3 is a halogen atom (chlorine atom, bromine atom and iodine atom) , a methanesulfonyloxy group, a
benzenesulfonyloxy group, a toluenesulfonyloxy group, a methoxysulfonyloxy group/ or an ethoxysulfonyloxy group.
The reaction is usually performed in a solvent in the presence of a base.
Examples of the solvent used in the reaction include ketones such as acetone, methyl ethyl ketone and the like, aromatic hydrocarbons such as benzene, toluene, xylene and the like, aliphatic hydrocarbons such as hexane, heptane and the like, ethers such as diethyl ether, tetrahydrofuran, 1, 4-dioxane, 1, 2-dimethoxyethane, 1, 2-diethoxyethane and the like, halogenated hydrocarbons such as chloroform, chlorobenzene, dichlorobenzene and the like, nitriles such as acetonitrile and the like, aprotic polar solvents such as N, N-dimethylformamide, N, N-dimethylacetamide, 1-methyl- 2-pyrrolidone, 1, 3-dimethylimidazolinone, dimethyl
sulfoxide and the like, water, and a mixture thereof.
Examples of the base used in the reaction include hydroxides of an alkali metal or an alkaline earth metal such as sodium hydroxide, potassium hydroxide, calcium hydroxide and the like, hydrides of an alkali metal or an alkaline earth metal such as sodium hydride, potassium hydride, calcium hydride and the like, carbonates of an alkaTi metal or an alkaline earth metal such as sodium carbonate, potassium carbonate and the like, alcoholates of an alkali metal such as sodium ethylate, sodium methylate and the like, organic lithium such as normalbutyllithium, lithium diisopropylamide and the like, and organic bases such as triethylamine, pyridine, 1,8- diazabicyclo [5.4.0] undec-7-ene and the like.
Each reagent may be used in an excess amount in the reaction, when the reagent is liquid under reaction
conditions. However, usually, the compound represented by the formula (X) is used at a proportion of 1 to 4 moles, and the base is used at a proportion of 1 to 4 moles based on 1 mole of the compound represented by formula (1-3).
The reaction temperature is usually in a range of -78 to 15O0C, and the reaction time is usually in a range of 0.1 to 100 hours.
After completion of the reaction, the compound
represented by the formula (1-5) can be isolated by
performing a post-treatment procedure such as by pouring the reaction mixture into water, extracting this with an organic solvent, and drying and concentrating the organic layer. The isolated compound represented by the formula (1-5) can be further purified by recrystallization, column chromatography or the like.
Process 7
"Among the compounds (I), a compound represented by the formula (I-β) :
Figure imgf000156_0001
wherein R2, R7 and Q are as defined above,
R1"4 is a hydrogen atom,
a formyl group,
a cyano group,
a lower alkyl group optionally substituted with one or more substituents,
a lower alkenyl group optionally substituted with one or more substituents, a lower alkynyl group optionally substituted with one or more substituents,
a lower cycloalkyl group optionally substituted with one or more substituents,
an aryl lower alkyl group optionally substituted with one or more substituents,
an aryl group optionally substituted with one or more substituents,
a lower alkoxy lower alkyl group optionally substituted with one or more substituents,
an aryloxy lower alkyl group optionally substituted with one ό~r more substituents,
a mono or di (lower alkyl) amino lower alkyl group optionally substituted with one or more substituents,
a lower alkanoyl group optionally substituted with one or more substituents,
a lower alkoxycarbonyl group optionally substituted with one or more substituents,
an aryloxycarbonyl group optionally substituted with one or more substituents,
an aryl lower alkoxycarbonyl group optionally substituted with one or more substituents,
a carbamoyl group optionally substituted with one or more substituents,
a thiocarbamoyl group optionally substituted with one or more substituents,
a lower alkoxyoxalyl group optionally substituted with one or more substituents,
an aryl lower alkoxyoxalyl group optionally substituted with one or more substituents,
an aryloxyoxalyl group optionally substituted with one or more substituents,
an aminooxalyl group optionally substituted with one or more substituents,
a lower alkoxy group optionally substituted with one or more substituents,
an afyloxy group optionally substituted with one or more substituents,
an aryl lower alkoxy group optionally substituted with one or more substituents, or
an amino group optionally substituted with one or more substituents,
A1 is a group represented by OR3 (wherein R3 is as defined above) or NR5R6 (wherein R5 and R6 are as defined above),
one of R7 's is a group represented by -SO-Z1
(wherein Z1 is a lower alkyl group optionally substituted with one or more halogen atoms, a lower alkenyl group optionally substituted with one or more halogen atoms, a lower alkynyl group optionally substituted with one or more halogen atoms, a phenyl group, or an aromatic heterocyclic group) , and
p is an integer of 0 to 3,
can be produced by subjecting a compound (XI) :
Figure imgf000159_0001
wherein R1'4, R2, R7, Q, A1, Z1 and p are as defined above, to an oxidation reaction.
The reaction is usually performed in a solvent in the presence of an oxidizing agent.
Examples of the solvent used in the reaction include ketones such as acetone, methyl ethyl ketone and the like, aromatic hydrocarbons such as benzene, toluene, xylene and the like, aliphatic hydrocarbons such as hexane, heptane and the like, ethers such as diethyl ether, tetrahydrofuran, 1,4-dioxane, 1, 2-dimethoxyethane, 1, 2-diethoxyethane and the like, halogenated hydrocarbons such as chloroform, chlorobenzene, dichlorobenzene and the like, nitriles such as acetonitrile and the like, organic acids such as acetic acid and the like, aprotic polar solvents such as N,N- dimethylformamide, N, N-dimethylacetamide, l-methyl-2- pyrrolidone, 1, 3-dimethylimidazolinone and the like, water, and a mixture thereof. Examples of the oxidizing agent used in the reaction include meta-chloroperbenzoic acid, and peroxides such as hydrogen peroxide and the like.
The oxidizing agent is usually used at a proportion of 1 to 1.5 moles based on 1 mole of the compound represented by the formula (XI) .
The reaction temperature is usually in a range of -78 to 1500C, and the reaction time is usually in a range of 0.1 to 100 hours.
After completion of the reaction, the compound
represented by "the formula (I-β) can be isolated by
performing a post-treatment procedure such as by pouring the reaction mixture into water, extracting this with an organic solvent, and drying and concentrating the organic layer. The isolated compound represented by the formula
(1-6) can be further purified by recrystallization, column chromatography or the like.
Process 8
Among the compounds (I), a compound represented by the formula (1-7) :
Figure imgf000160_0001
wherein X, Y, R2, R7, Z1, R1"4, A1, Q and p are as defined above , and
one of R7' s is a group represented by -SO2-Z1
(wherein Z1 is a lower alkyl group optionally substituted with one -or more halogen atoms, a lower alkenyl group optionally substituted with one or more halogen atoms, a lower alkynyl group optionally substituted with one or more halogen atoms, a phenyl group, or an aromatic heterocyclic group) ,
can be produced by subjecting a compound represented by the formula (XII) :
Figure imgf000161_0001
wherein R1"4, R2, R7, Z1, A1, Q and p are as defined above, and
1 is an integer of 0 or 1,
to an oxidation reaction.
The reaction is usually performed in a solvent in the presence of an oxidizing agent.
Examples of the solvent used in the reaction include ketones such as acetone, methyl ethyl ketone and the like, aromatic hydrocarbons such as benzene, toluene, xylene and the like, aliphatic hydrocarbons such as hexane, heptane and the like, ethers such as diethyl ether, tetrahydrofuran, 1, 4-dioxane, 1, 2-dimethoxyethane, 1, 2-diethoxyethane and the like, halogenated hydrocarbons such as chloroform, chlorobenzene, dichlorobenzene and the like, nitriles such as acetonitrile and the like, organic acids such as acetic acid and the like, aprotic polar solvents such as N,N- dimethylformamide, N, N-dimethylacetamide, l-methyl-2- pyrrolidone, 1, 3-dimethylimidazolinone and the like, water, and a mixture thereof.
Examples of the oxidizing agent used in the reaction include meta-chloroperbenzoic acid, and peroxides such as hydrogen peroxide and the like.
NThe oxidizing agent is usually used at a proportion of 2 to 10 moles based on 1 mole of the compound represented by the formula (XI) .
The reaction temperature is usually in a range of -78 to 150°C, and the reaction time is usually in a range of 0.1 to 100 hours.
After completion of the reaction, the compound
represented by the formula (1-7) can be isolated by
performing a post-treatment procedure such as by pouring the reaction mixture into water, extracting this with an organic solvent, and drying and concentrating the organic layer. The isolated compound represented by the formula (1-7) can be further purified by recrystallization, column chromatography or the like. Process 9
Among the compounds (I), a compound' represented by the formula (1-8) :
Figure imgf000163_0001
wherein X, R2, R7, A, Q and m are as defined above, and
R1"5 is a lower alkyl group optionally 'substituted with one or more substituents,
a lower alkenyl group optionally substituted with one or more substituents,
a lower alkynyl group optionally substituted with one or more substituents,
a lower cycloalkyl group optionally substituted with one or more substituents,
an aryl lower alkyl group optionally substituted with one or more substituents,
an aryl group optionally substituted with one or more substituents,
a lower alkoxy lower alkyl group optionally substituted with one or more substituents,
an aryloxy lower alkyl group optionally substituted with one or more substituents,
a lower alkylthio lower alkyl group optionally substituted with one or more substituents, a lower alkylsulfinyl lower alkyl group optionally
substituted with one or more substituents,
a lower alkylsulfonyl lower alkyl group optionally
substituted with one or more substituents,
a mono or di (lower alkyl) amino lower alkyl group optionally substituted with one or more substituents,
a lower alkoxy group optionally substituted with one or more substituents,
an aryloxy group optionally substituted with one or more substituents,
an aryl lower alkoxy group optionally substituted with one or more substituents,
an amino group optionally substituted with one or more substituents, or
a heterocyclic group optionally substituted with one or more substituents,
can be produced by reacting a compound represented by the formula (XIII) :
Figure imgf000164_0001
wherein R2, R7, A, m and R1"5 are as defined above,
with a compound represented by the formula (XIV) :
Figure imgf000164_0002
( XIV) wherein X and Q are as defined above, and
L3 is a halogen atom (chlorine atom', bromine atom and iodine atom) .
The .reaction is usually performed in a solvent in the presence of a base.
Examples ~of the solvent used in the reaction include ketones such as acetone, methyl ethyl ketone and the like, aromatic hydrocarbons such as benzene, toluene, xylene and the like, aliphatic hydrocarbons such as hexane, heptane and the like, ethers such as diethyl ether, tetrahydrofuran, 1,4-dioxane, 1, 2-dimethoxyethane, 1, 2-diethoxyethane and the lake, halogenated hydrocarbons such as chloroform, chlorobenzene, dichlorobenzene and the like, nitriles such as acetonitrile and the like, aprotic polar solvents such as N, N-dimethylformamide, N, N-dimethylacetamide, 1-methyl- 2-pyrrolidone, 1, 3-dimethylimidazolinone, dimethyl
sulfoxide and the like, water, and a mixture thereof.
Examples of the base used in the reaction include hydroxides of an alkali metal or an alkaline earth metal such as sodium hydroxide, potassium hydroxide, calcium hydroxide and the like, hydrides of an alkali metal or an alkaline earth metal such as sodium hydride, potassium hydride, calcium hydride and the like, carbonates of an alkali metal or an alkaline earth metal such as sodium carbonate, potassium carbonate and the like, alcoholates of an alkali metal such as sodium ethylate, sodium methylate and the like, organic lithium such as normalbutyllithium, lithium diisopropylamide and the like, and organic bases such as triethylamine, pyridine, 1,8- diazabicyclo [5.4.0] undec-7-ene and the like.
Each reagent may be used in an excess amount in the reaction, when the reagent is liquid under reaction
conditions. However, usually, the compound represented by the formula (XIV) is used at a proportion of 1 to 4 moles, and the base is used at a proportion of 1 to 4 moles based on 1 mole of the compound represented by the formula (XIII)
'The reaction temperature is usually in a range of -78 to 150°C, and the reaction time is usually in a range of 0.1 to 200 hours.
After completion of the reaction, the compound
represented by the formula (1-8) can be isolated by
performing a post-treatment procedure such as by pouring the reaction mixture into water, extracting this with an organic solvent, and drying and concentrating the organic layer. The isolated compound represented by the formula
(1-8) can be further purified by recrystallization, column chromatography or the like.
Process 10
Among the compounds (I), a compound represented by the formula (1-9) :
Figure imgf000167_0001
wherein R2, R7 and Q are as defined above,
R1"6 is a lower alkyl group optionally substituted with one or more substituents,
a lower alkenyl group optionally substituted with one or more substituents,
a lower alkynyl group optionally substituted with one or more substituents,
a lower cycloalkyl group optionally substituted with one or more ^substituents,
an aryl lower alkyl group optionally substituted with one or more substituents,
an aryl group optionally substituted with one or more substituents,
a lower alkoxy lower alkyl group optionally substituted with one or more substituents,
an aryloxy lower alkyl group optionally substituted with one or more substituents,
a mono or di (lower alkyl) amino lower alkyl group optionally substituted with one or more substituents,
a lower alkoxy group optionally substituted with one or more substituents,
an aryloxy group optionally substituted with one or more substituents,
an aryl lower alkoxy group optionally substituted with one or more substituents,
an amino group optionally substituted with one or more substituents, or
a heterocyclic group optionally substituted with one or more substituents,
A2 is a group represented by NR5R6 (wherein R5 and R6 are as defined above) , and
m is an integer of 1 to 5,
can be produced by reacting a compound represented by the formula (XV) :
Figure imgf000168_0001
wherein R1"6, R2, R7, Q and m are as defined above, and
L4 is a halogen atom (chlorine atom, bromine atom and iodine atom) ,
with a compound represented by the formula (XVI):
H-A2
(XVI) wherein A2 is as defined above.
The reaction is usually performed in a solvent in the presence of a base.
Examples of the solvent used in the reaction include ketones such as acetone, methyl ethyl ketone and the like, aromatic hydrocarbons such as benzene, toluene, xylene and the like, aliphatic hydrocarbons such as hexane, heptane and the like, ethers such as diethyl ether, tetrahydrofuran, 1,4-dioxane, 1, 2-dimethoxyethane, 1, 2-diethoxyethane and the like, halogenated hydrocarbons such as chloroform, chlorobenzene, dichlorobenzene and the like, nitriles such as acetonitrile and the like, aprotic polar solvents such as N, N-dimethylformamide, N, N-dimethylacetamide, 1-methyl- 2-pyrrolidone, 1, 3-dimethylimidazolinone, dimethyl
sulfoxide and the like, water, and a mixture thereof.
x,Examples of the base used in the reaction include hydroxides of an alkali metal or an alkaline earth metal such as sodium hydroxide, potassium hydroxide, calcium hydroxide and the like, hydrides of an alkali metal or an alkaline earth metal such as sodium hydride, potassium hydride, calcium hydride and the like, carbonates of an alkali metal or an alkaline earth metal such as sodium carbonate, potassium carbonate and the like, alcoholates of an alkali metal such as sodium ethylate, sodium methylate and the like, organic lithium such as normalbutyllithium, lithium diisopropylamide and the like, and organic bases such as triethylamine, pyridine, 1,8- diazabicyclo [5.4.0] undec-7-ene and the like.
Each reagent may be used in an excess amount in the reaction, when the reagent is liquid under reaction
conditions. However, usually, the compound represented by the formula (XVI) is used at a proportion of 1 to 4 moles, and the base is used at a proportion of 1 to 4 moles based on 1 mole of the compound represented by the formula (XV) .
The reaction temperature is usually in a range of -78 to 150°C, and the reaction time is usually in a range of 0.1 to 200 hours.
After completion of the reaction, the compound
represented by the formula (1-9) can be isolated by
performing a post-treatment procedure such as by pouring the Reaction mixture into water, extracting this with an organic solvent, and drying and concentrating the organic layer. The isolated compound represented by the formula (1-9) can be further purified by recrystallization, column chromatography or the like.
The compound represented by the formula (XV) can be produced by the process of Process (9), Reference Process 2 or Reference Process 3, or modification thereof.
Then, processes for producing intermediate compounds used in the production of the compound (I) will be
explained.
Reference Process 1
The compound represented by the formula (IX) can be produced by reaction of a compound represented by the formula (XVII) :
Figure imgf000171_0001
wherein Q and R1"2 are as defined above, with a
trialkylchlorosilane, and a chlorocarbonylating agent or a chlorothiocarbonylating agent.
The reaction is usually performed in a solvent in the presence of a base.
Examples of the solvent used in the reaction include ketones such as acetone, methyl ethyl ketone and the like, aromatic hydrocarbons such as benzene, toluene, xylene and the like, aliphatic hydrocarbons such as hexane, heptane and the like, ethers such as diethyl ether, tetrahydrofuran, 1,4-dioxane, 1, 2-dimethoxyethane, 1, 2-diethoxyethane and the like, halogenated hydrocarbons such as chloroform, chlorobenzene, dichlorobenzene and the like, nitriles such as acetonitrile and the like, aprotic polar solvents such as N, N-dimethylformamide, N, N-dimethylacetamide, 1-methyl- 2-pyrrolidone, 1, 3-dimethylimidazolinone, dimethyl
sulfoxide and the like, water, and a mixture thereof.
Examples of the base used in the reaction include hydroxides of an alkali metal or an alkaline earth metal such as sodium hydroxide, potassium hydroxide, calcium hydroxide and the like, hydrides of an alkali metal or an alkaline earth metal such as sodium hydride, potassium hydride, calcium hydride and the like, carbonates of an ^ alkali metal or an alkaline earth metal such as sodium carbonate, potassium carbonate and the like, alcoholates of an alkali metal such as sodium ethylate, sodium methylate and the like, organic lithium such as normalbutyllithium, lithium diisopropylamide and the like, and organic bases such as triethylamine, pyridine, 1,8- diazabicyclo [5.4.0] undec-7-ene and the like.
Examples of the trialkylchlorosilane compound used in the reaction include trimethylchlorosilane, and
triethylchlorosilane .
Examples of the chlorocarbonizing agent used in the reaction include phosgene, trichloromethyl chloroformate, and bis (trichloromethyl) carbonate .
Examples of the chlorothiocarbonizing agent used in the reaction include thiophosgene .
Usually, the trialkylchlorosilane is used at a
proportion of 1 to 4 moles, the chlorocarbonizing agent or the chlorothiocarbonizing agent is used at a proportion of 1 to 4 moles, and the base is used at a proportion of 1 to 4 moles based on 1 mole of the compound represented by the formula (XVII) .
The reaction temperature is usually in a range of -78 to 15O0C, and the reaction time is usually in a range of 0.1 to 200 hours.
After completion of the reaction, the compound ^ represented by the formula (IX) can be isolated by
performing a post-treating procedure such as by
concentrating a reaction mixture as it is. The isolated compound represented by the formula (IX) can be used in the next step without purification.
Reference Process 2
The compound represented by the formula (XIII) :
Figure imgf000173_0001
wherein R2, R7, A, m and R1"5 are as defined above,
can be produced by reacting a compound represented by the formula (XVIII) :
Figure imgf000173_0002
wherein R2, R7, A and m are as defined above,
with a compound represented by the formula (XIX) :
H2N-R1"5
(XDC) wherein R1"5 is as defined above.
The reaction is usually performed in a solvent in the presence of a base. Examples of the solvent used in the reaction include ketones such as acetone, methyl ethyl ketone and the like,v aromatic hydrocarbons such as benzene, toluene, xylene and the like,- aliphatic hydrocarbons such as hexane, heptane and the like, ethers such as diethyl ether, tetrahydrofuran, 1,4-dioxane, ϊ, 2-dimethoxyethane, 1, 2-diethoxyethane and the like, halogenated hydrocarbons such as chloroform, chlorobenzene, dichlorobenzene and the like, nitriles such as acetonitrile and the like, aprotic polar solvents such as N, N-dimethylformamide, N, N-dimethylacetamide, 1-methyl- 2-pyrrolidone, 1, 3-dimethylimidazolinone, dimethyl
sulfoxide and the like, water, and a mixture thereof.
Examples of the base used in the reaction include hydroxides of an alkali metal or an alkaline earth metal such as sodium hydroxide, potassium hydroxide, calcium hydroxide and the like, hydrides of an alkali metal or an alkaline earth metal such as sodium hydride, potassium hydride, calcium hydride and the like, carbonates of an alkali metal or an alkaline earth metal such as sodium carbonate, potassium carbonate and the like, alcoholates of an alkali metal such as sodium ethylate, sodium methylate and the like, organic lithium such as normalbutyllithium, lithium diisopropylamide and the like, and organic bases such as triethylamine, pyridine, 1,8- diazabicyclo [5.4.0] undec-7-ene and the like. Usually, the compound represented by the formula (XIX) is used at a proportion of 1 to 6 moles, and the base is used at a proportion of 1 mole to an excessive amount based on 1 mole of the compound represented by the formula
(XVIII) .
The reaction temperature is usually in a range of -78 to 150°C, and the reaction time is usually in a range of 0.1 to 200 hours.
After completion of the reaction, the compound (XIII) can be isolated by performing a post-treatment procedure such as by pouring the reaction mixture into water,
extracting this with an organic solvent, and drying and concentrating the organic layer. The isolated compound (XIII) can be further purified by recrystallization, column chromatography or the like. The isolated compound (XIII) can be used in the next step without purification.
Reference Process 3
The compound represented by the formula (XVIII) :
Figure imgf000175_0001
wherein R2, R7, A and m are as defined above,
can be produced by reacting the compound represented by the formula (VIII) :
Figure imgf000176_0001
wherein A, R2, R7 and m are as defined above,
with a chlorocarbonizing agent.
The reaction is usually performed in a solvent in the presence of a base.
Examples of the solvent used in the reaction include ketones such as acetone, methyl ethyl ketone and the like, aromatic hydrocarbons such as benzene, toluene, xylene and the like, aliphatic hydrocarbons such as hexane, heptane and the like, ethers such as diethyl ether, tetrahydrofuran, 1,4-dioxane, 1, 2-dimethoxyethane, 1, 2-diethoxyethane and the like, halogenated hydrocarbons such as chloroform, chlorobenzene, dichlorobenzene and the like, nitriles such as acetonitrile and the like, aprotic polar solvents such as N,N-dimethylformamide, N, N-dimethylacetamide, 1-methyl- 2-pyrrolidone, 1, 3-dimethylimidazolinone, dimethyl
sulfoxide and the like, water, and a mixture thereof.
Examples of the base used in the reaction include hydroxides of an alkali metal or an alkaline earth metal such as sodium hydroxide, potassium hydroxide, calcium hydroxide and the like, hydrides of an alkali metal or an alkaline earth metal such as sodium hydride, potassium hydride, calcium hydride and the like, carbonates of an alkali metal or an alkaline earth metal such as sodium carbonate, potassium carbonate and the like, alcoholates of an alkali metal such as sodium ethylate, sodium methylate and the like, organic lithium such as normalbutyllithium, lithium diisopropylamide and the like, and organic bases such as triethylamine, pyridine, 1,8- diazabicyclo [5.4.0] undec-7-ene and the like.
Examples of the chlorocarbonizing agent used in the reaction include phosgene, trichloromethyl chloroformate, and bis (trichloromethyl) carbonate .
Usually, the chlorocarbonizing agent is used at a proportion of 1 to 4 moles, and the base is used at a proportion of 1 to 4 moles based on 1 mole of the compound represented by the formula (VIII) .
The reaction temperature is usually in a range of -78 to 180°C, and the reaction time is usually in a range of 0.1 to 200 hours.
After completion of the reaction, the compound
represented by the formula (XVIII) can be isolated by performing a post-treatment procedure such as by
concentrating the reaction mixture as it is. The isolated compound represented by the formula (XVIII) can be used in the next step without purification.
Reference Process 4
The compound represented by the formula (XV) :
Figure imgf000178_0001
wherein R1"6, R2, R7, Q, L4 and m are as defined above, can be produced by reacting a compound represented by the formula (XX) : "
Figure imgf000178_0002
wherein R1" 6 , R2 , R7 , L4 and m are as de f ined above ,
with a compound represented by the formula ( XXI ) :
Figure imgf000178_0003
wherein Q is as defined above, and
L3 is a halogen atom (chlorine atom, bromine atom and iodine atom) .
The reaction is usually performed in a solvent in the presence of a base.
Examples of the solvent used in the reaction include ketones such as acetone, methyl ethyl ketone and the like, aromatic hydrocarbons such as benzene, toluene, xylene and the like, aliphatic hydrocarbons such as hexane, heptane and the like, ethers such as diethyl ether, tetrahydrofuran, 1,4-dioxane, 1, 2-dimethoxyethane, 1, 2-diethoxyethane and the like, halogenated hydrocarbons such as chloroform, chlorobenzene, dichlorobenzene and the like, nitriles such as acetonitrile and the like, aprotic polar solvents such ^ as N,N-dimethylformamide, N, N-dimethylacetamide, 1-methyl- 2-pyrrolidone, 1, 3-dimethylimidazolinone, dimethyl
sulfoxide and the like, water, and a mixture thereof.
Examples of the base used in the reaction include hydroxides of an alkali metal or an alkaline earth metal such as sodium hydroxide, potassium hydroxide, calcium hydroxide and the like, hydrides of an alkali metal or an alkaline earth metal such as sodium hydride, potassium hydride, calcium hydride and the like, carbonates of an alkalU metal or an alkaline earth metal such as sodium carbonate, potassium carbonate and the like, alcoholates of an alkali metal such as sodium ethylate, sodium methylate and the like, organic lithium such as normalbutyllithium, lithium diisopropylamide and the like, and organic bases such as diisopropyl ethylamine, triethylamine, pyridine, 1, 8-diazabicyclo [5.4.0] undec-7-ene and the like.
Each reagent may be used at an excess amount in the reaction, when the reagent is liquid under reaction
conditions. However, usually, the compound represented by the formula (XXI) is used at a proportion of 1 to 4 moles, and the base is used at a proportion of 1 to 4 moles based on 1 mole of the compound represented by the formula (XX) .
The reaction temperature is usually in a range of -78 to 1500C, and the reaction time is usually in a range of 0.1 to 200 hours.
After completion of the reaction, the compound represented by the formula (XV) can be isolated by performing a post-treatment procedure such as by pouring the reaction mixture into water, extracting this with an organic solvent, and drying and concentrating the organic layer. The isolated compound represented by the formula (XV) can be further purified by recrystallization, column chromatography or the like.
Reference Process 5
xιThe compound represented by the formula (XX) :
Figure imgf000180_0001
wherein R2, R7, L4, m and R1"6 are as defined above, can be produced by reacting a compound represented by the formula (XXII) :
Figure imgf000180_0002
wherein R2, R7, L4 and m are as defined above,
with a compound represented by the formula (XXIII):
H2N-R1"6
(XXIII) wherein R1"6 is as defined above.
The reaction is usually performed in a solvent in the presence of a base.
Examples of the solvent used in the reaction include ketones such as acetone, methyl ethyl ketone and the like, aromatic hydrocarbons such as benzene, toluene, xylene and the like, aliphatic hydrocarbons such as hexane, heptane and the like, ethers such as diethyl ether, tetrahydrofuran, 1,4-dioxane, 1, 2-dimethoxyethane, 1, 2-diethoxyethane and the like, halogenated hydrocarbons such as chloroform, chlorobenzene, dichlorobenzene and the like, nitriles such as acvetonitrile and the like, aprotic polar solvents such as N, N-dimethylformamide, N, N-dimethylacetamide, 1-methyl- 2-pyrrolidone, 1, 3-dimethylimidazolinone, dimethyl
sulfoxide and the like, water, and a mixture thereof.
Examples of the base used in the reaction include hydroxides of an alkali metal or an alkaline earth metal such as sodium hydroxide, potassium hydroxide, calcium hydroxide and the like, hydrides of an alkali metal or an alkaline earth metal such as sodium hydride, potassium hydride, calcium hydride and the like, carbonates of an alkali metal or an alkaline earth metal such as sodium carbonate, potassium carbonate and the like, alcoholates of an alkali metal such as sodium ethylate, sodium methylate and the like, organic lithium such as normalbutyllithium, lithium diisopropylamide and the like, and organic bases such as triethylamine, pyridine, 1,8- diazabicyclo [5.4.0] undec-7-ene and the like.
Usually, the compound represented by the formula (XXIII) is used at a proportion of 1 to 6 moles, and the base is used at a proportion of 1 to 6 moles based on 1 mole of the compound represented by the formula (XXII).
The reaction temperature is usually in a range of -78 to 15O0C, and the reaction time is usually in a range of 0.1 to 200 hours.
After completion of the reaction, the compound represented by the formula (XX) can be isolated by
performing a post-treatment procedure such as by pouring the reaction mixture into water, extracting this with an organic solvent, and drying and concentrating the organic layer. The isolated compound represented by the formula (XX) can be further purified by recrystallization, column chromatography or the like. The isolated compound
represented by the formula (XX) can be also used in the next step without purification.
Reference Process 6
The compound represented by the formula (XXII) :
Figure imgf000182_0001
wherein R2, R7, L4 and m are as defined above,
can be produced by reacting a compound represented by the formula (XXIV) :
Figure imgf000183_0001
wherein L4, R2, R7 and m are as defined above,
with a chlorocarbonizing agent.
The reaction is usually performed in a solvent in the presence of a base.
Examples of the solvent used in the reaction include ketones such as acetone, methyl ethyl ketone and the like, aromatic hydrocarbons such as benzene, toluene, xylene and the like, aliphatic hydrocarbons such as hexane, heptane and the like, ethers such as diethyl ether, tetrahydrofuran, 1,4-dioxane, 1, 2-dimethoxyethane, 1, 2-diethoxyethane and the like, halogenated hydrocarbons such as chloroform, chlorobenzene, dichlorobenzene and the like, nitriles such as acetonitrile and the like, aprotic polar solvents such as N, N-dimethylformamide, N, N-dimethylacetamide, 1-methyl- 2-pyrrolidone, 1, 3-dimethylimidazolinone, dimethyl
sulfoxide and the like, water, and a mixture thereof.
Examples of the base used in the reaction include hydroxides of an alkali metal or an alkaline earth metal such as sodium hydroxide, potassium hydroxide, calcium hydroxide and the like, hydrides of an alkali metal or an alkaline earth metal such as sodium hydride, potassium hydride, calcium hydride and the like, carbonates of an alkali metal or an alkaline earth metal such as sodium carbonate, potassium carbonate and the like, alcoholates of an alkali metal such as sodium ethylate, sodium methylate and the like, organic lithium such as normalbutyllithium, lithium diisopropylamide and the like, and organic bases such as triethylamine, pyridine, 1,8- diazabicyclo [5.4.0] undec-7-ene and the like.
Examples of the chlorocarbonizing agent used in the reaction include phosgene, trichloromethyl chloroformate, and bis (trichloromethyl) carbonate.
Usually, the chlorocarbonizing agent is used at a proportion of 1 to 4 moles, and the base is used at a proportion of 1 to 4 moles based on 1 mole of the compound represented by the formula (XXIV) .
The reaction temperature is usually in a range of -78 to 180°C, and the reaction time is usually in a range of 0.1 to 200 hours.
After completion of the reaction, the compound
represented by the formula (XXII) can be isolated by performing a post-treatment procedure such as by
concentrating the reaction mixture as it is. The isolated compound represented by the formula (XXII) can be used in the next step without purification.
The compound represented by the formula (XXIV) can be produced by the process described, for example, in Journal of Pesticide Science 23(3) (1998) P250-254, or modification thereof.
The compounds produced by the above Processes or the like may be further subjected to known per se methods such as alkylation, alkenylation, alkynylation, acylation, amination, sulfidization, sulfinylation, sulfonation, oxidation, reduction, halogenation, nitration and the like to convert substituents thereof into other substituents .
The compounds obtained by Processes 1 to 10 and
Reference Processes 1 to 6 can be isolated and purified by methods such as recrystallization, column chromatography, high performance liquid chromatography, medium pressure preparative high performance liquid chromatography, desalting resin column chromatography, reprecipitation and the like.
In the compound (I), an acidic group such as a
hydroxyoxalyl group or the like as its substituent in the molecule thereof can form an agrochemically acceptable base salt with an inorganic base or an organic base. A basic group such as a dialkylamino group as its substituent in the molecule thereof can form an agrochemically acceptable acid addition salt with an inorganic acid, or an organic acid .
A preferable salt of the compound (I) is an
agrochemically acceptable acid addition salt formed by a basic group such as a dialkylamino group or the like as its substituent in the molecule thereof with an inorganic acid, an organic acid or the like.
Examples of the inorganic acid addition salt include salts with hydrochloric acid, hydrobromic acid, hydriodic acid, sulfuric acid, nitric acid, phosphoric acid and perchloric acid, examples of the organic acid addition salt include salts with formic acid, acetic acid, propionic acid, oxalixc acid, succinic acid, benzoic acid, para- toluenesulfonic acid, methanesulfonic acid and
trifluoroacetic acid, and examples of the inorganic base salt include salts with an alkali metal (sodium, potassium etc.), an alkali earth metal (calcium etc.) and ammonia. Examples of the organic base salt include salts with
dimethylamine, triethylamine, N, N-dimethylaniline,
piperazine, pyrrolidine, piperidine, pyridine, 2- phenylethylamine, benzylamine, ethanolamine, diethanolamine and 1, 8-diazabicyclo [5,4,0] undecene.
A salt of the compound (I) can be obtained by mixing the compound (I) and an acid or a base.
When R1 of the compound (I) is a hydrogen atom, an agrochemically acceptable salt can be formed with an anion produced by dissociation of this hydrogen atom and a metal cation. Examples of such salt include salts with an alkali metal (sodium, potassium etc.), or an alkaline earth metal (calcium etc.). Alternatively, when R1 of the compound (I) is a hydrogen atom, an agrochemically acceptable addition salt can be formed with the compound (I) and an inorganic base or an organic base. Examples of such salt include addition salts with an inorganic base such as ammonia and the like, and addition salts with an organic base such as dimethylamine, triethylamine, N, N-dimethylaniline,
piperazine, pyrrolidine, piperidine, pyridine, 2- phenylethylamine, benzylamine, ethanolamine, diethanolamine, and 1, 8-diazabicyclo [5, 4 , 0] undecene .
The pesticide for controlling and preventing harmful organisms of the present invention may be the compound (I) or its salt itself, but is usually prepared, if necessary, by adding a surfactant or other auxiliary agent for
preparation, as an emulsion, a solution, a microemulsion, a flowable formulation, an oil solution, a wettable powder, a water solble power, a sol formulation, a powder, a granule, a fine granule, a seed coating agent, an
immersion coating formulation, a smoking agent, an
aerosol, a tablet, a microcapsule, a spray formulation, an EW agent, an ointment, a poison bait, a capsule, a pellet, a film coating formulation, a painting formulation, an injectable, a shampoo preparation or the like, which contains the compound (I) or' a salt thereof and inert carriers such as a solid carrier, a liquid carrier and a gaseous carrier.
Examples of the liquid carrier used for preparation include water," alcohols (for example, methyl alcohol, ethyl alcohol, n-propyl alcohol, isopropyl alcohol, ethylene glycol and the like), ketones (for example/ acetone, methyl ethyl ketone, methyl isobutyl ketone, cyclohexanone and the like), ethers (for example, tetrahydrofuran, ethylene glycol monomethyl ether, diethylene glycol monomethyl ether, propylene glycol monomethyl ether and the like) , aliphatic hydrocarbons (for example, kerosine, fuel oil, machine oil and the like), aromatic hydrocarbons (for example, toluene, xylene, solvent naphtha, methyl naphthalene and the like) , halogenated hydrocarbons (for example, dichloromethane, chloroform, carbon tetrachloride and the like) , acid amides (for example, N, N-dimehylformamide, N, N-dimethylacetoamide, N-methylpyrrolidone and the like), esters (for example, ethyl acetate, butyl acetate, fatty glycerin ester, γ- butylolactone and the like), and nitriles (for example, acetonitrile, propyonitrile and the like) .
Examples of the solid carrier include vegetable powder (for example, soybean powder, tobacco powder, wheat powder, woodmeal and the like) , mineral powder (for example, clays such as kaolin, bentonite, acid clay and the like, talcs such as talc powder, agalmatolite powder and the like, silicas such as diatomaceous earth, mica powder and the like) , alumina, sulfur powder, activated carbon, calcium carbonate, ammonium sulfate, sodium hydrogen carbonate, lactose and urea.
In addition, examples of the ointment base include polyethylene glycol; pectin; polyhydric alcohol ester of higher fatty acid such as monostearic acid glycerin ester and the like; cellulose derivatives such as
methylcellulose and the like; sodium alginate; bentonite; higher alcohol; polyhydric alcohol such as glycerin and the like; vaseline; white vaseline; liquid paraffin;
lard; various vegetable oils; lanolin; dehydrated
lanolin; hardened oil; resins and a mixture of these and a surfactant .
Examples of the surfactant include nonionic and anionic surfactants such as soaps, polyoxyethylene alkyl aryl ethers [e.g. Neugen (trade name), E• A142 (trade name); manufactured by Dai-ichi Kogyo Seiyaku Co., Ltd.,
Nonal (trade name); manufactured by Toho Chemical
Industries Co., Ltd.], alkyl sulfate salts [e.g. Emar 10 (trade name) , Emar 40 (trade name) ; manufactured by Kao
Corporation], alkylbenzene sulfonic acid salts [e.g.
Neogen (trade name), Neogen T (trade name); manufactured by Dai-ichi Kogyo Seiyaku Co., Ltd., Neoperex;
manufactured by Kao Corporation] , polyethylene glycol ethers [e.g., Nonipol 85 (trade name), Nonipol 100 (trade name) , Nonipol 160 (trade name) ; manufactured by Sanyo Chemical Industries, Ltd.], polyhydric alcohol esters [e.g. Tween 20 (trade name), Tween 80 (trade name);
manufactured by Kao Corporation] , alkylsulfosuccinic acid salts [e.g. Sanmolin OT20 (trade name); manufactured by Sanyo Chemical Industries, Ltd.], alkylnaphthalene
sulfonic acid salts [e.g. Newcalgen EX70 (trade name);
manufactured by Takemoto Oil & Fat Co., Ltd.], alkenyl sulfonic acid salts [e.g. Solpol 5115 (trade name);
manufactured by Toho Chemical Industries Co., Ltd.] and the like.
The ratio of the compound (I) or a salt thereof contained in the preparation of the pesticide of the present invention is usually 0.1 to 80% by weight, preferably 1 to 20% by weight relative to the total amount of pesticide of the present invention. Specifically, when the compound is used as an emulsion, a solution, a wettable powder or the like, usually about 1 to 80% by weight, preferably about 1 to 20% by weight is suitable. When used as an oil solution or a powder, usually about 0.1 to 50% by weight, preferably about 0.1 to 20% by weight is suitable. When used in a granule, usually about 5 to 50% by weight, preferably about 1 to 20% by weight is suitable.
The pesticide of the present invention can be used in admixture with other insecticides, acaricides, nematocides, fungicides, herbicides, plant growth regulators, synergists, attractants, repellents, safeners, pigments, fertilizers and the like.
Representative examples of the fungicides, plant growth regulators and herbicides that can be used by mixing with the pesticide of the present invention, and the
pesticide and the like such as insecticides, acaricides and rfematocides are shown below.
Active ingredients of the insecticide include, for example,
(1) Organic phosphorous compounds
Acephate, Aluminium phosphide, butathiofos, cadusafos, chlorethoxyfos, chlorfenvinphos, chlorpyrifos,
chlorpyrifos-methyl, cyanophos (CYAP) , diazinon, DCIP
(dichlorodiisopropyl ether) , dichlofenthion (ECP) ,
dichlorvos (DDVP) , dimethoate, dimethylvinphos, disulfoton,
EPN, ethion, ethoprophos, etrimfos, fenthion (MPP) ,
fenitrothion (MEP) , fosthiazate, formothion, Hydrogen phosphide, isofenphos, isoxathion, malathion, mesulfenfos, methidathion (DMTP), monocrotophos, naled (BRP),
oxydeprofos (ESP), parathion, phosalone, phosmet (PMP), pirimiphos-methyl, pyridafenthion, quinalphos, phenthoate (PAP), profenofos, propaphos, prothiofos*, pyraclorfos, salithion, sulprofos, tebupirimfos, temephos,
tetrachlorvinphos, terbufos, thiometon, trichlorphon (DEP), vamidothion and the like;
(2) Carbamate "compounds
Alanycarb, bendiocarb, benfuracarb, BPMC, carbaryl, carbofuran, carbosulfan, cloethocarb, ethiofencarb,
fenobucarb, fenothiocarb, fenoxycarb, furathiocarb,
isoprocarb (MIPC) , metolcarb, methomyl, methiocarb, NAC, oxamyl, pirimicarb, propoxur (PHC) , XMC, thiodicarb, xylyTcarb and the like;
(3) Synthetic pyrethroid compounds
Acrinathrin, allethrin, benfluthrin, beta-cyfluthrin, bifenthrin, cycloprothrin, cyfluthrin, cyhalothrin,
cypermethrin, deltamethrin, esfenvalerate, ethofenprox, fenpropathrin, fenvalerate, flucythrinate, flufenoprox, flumethrin, fluvalinate, halfenprox, imiprothrin,
permethrin, prallethrin, pyrethrins, resmethrin, sigma- cypermethrin, silafluofen, tefluthrin, tralomethrin, transfluthrin, 2, 3, 5, 6-tetrafluoro-4- (methoxymethyl) benzyl (EZ) - (IRS, 3RS; IRS, 3SR) -2, 2-dimethyl-3-prop-l- enylcyclopropanecarboxylate, 2,3,5, β-tetrafluoro-4- methylbenzyl (EZ) - ( IRS, 3RS; IRS, 3SR) -2, 2-dimethyl-3-prop-l- enylcyclopropanecarboxylate, 2, 3, 5, β-tetrafluoro-4- (methoxymethyl) benzyl (IRS, 3RS; IRS, 3SR) -2, 2-dimethyl-3- (2- methyl-1-propenyl) cyclopropanecarboxylate and the like;
(4) Nereistoxin compounds
Cartap, bensultap, thiocyclam, monosultap, bisultap and the like;
(5) Neonicotirioid compounds
Imidacloprid, nitenpyram, acetamiprid, thiamethoxam, thiacloprid, dinotefuran, clothianidin and 'the like;
(6) Benzoylurea compounds
Chlorfluazuron, bistrifluron, diafenthiuron,
diflubenzuron, fluazuron, flucycloxuron, flufenoxuron, hexaf\Lumuron, lufenuron, novaluron, noviflumuron,
teflubenzuron, triflumuron and the like;
(7) Phenylpyrazole compounds
Acetoprole, ethiprole, fipronil, vaniliprole,
pyriprole, pyrafluprole and the like;
(8) Bt toxins
Live spores and produced crystal toxin derived from bacillus thuringiensis, and a mixture thereof;
(9) Hydrazine compounds
Chromafenozide, halofenozide, methoxyfenozide, tebufenozide and the like;
(10) Organic chlorine compounds
Aldrin, dieldrin, dienochlor, endosulfan, methoxychlor and the like; (11) Natural insecticides
Machine oil, nicotine-sulfate and the like;
(12) other insecticides
Avermectin-B, bromopropylate, buprofezin,
chlorphenapyr, cyromazine, D-D (1, 3-Dichloropropene) , emamectin-benzoate, fenazaquin, flupyrazofos, hydroprene, indoxacarb, metoxadiazone, milbemycin-A, pymetrozine, pyridalyl, pyriproxyfen, spinosad, sulfluramid, tolfenpyrad, triazamate, flubendiamide, SI-0009, cyflumetofen, Arsenic acid, benclothiaz, Calcium cyanamide, Calcium polysulfide, chlordane, DDT, DSP, flufenerim, flonicamid, flurimfen, formeitanate, metarn-ammonium, metam-sodium, Methyl bromide, nidinotefuran, Potassium oleate, protrifenbute,
spiromesifen, Sulfur, metaflumizone, spirotetramat,
pyrifluquinazon, Chlorantraniliprole,
a compound represented by formula (A)
Figure imgf000194_0001
wherein, R1 represents a methyl group, a chlorine atom, a bromine atom or a fluorine atom, R2 represents a fluorine atom, a chlorine atom, a bromine atom, C1-4 haloalkyl group or Ci-4 haloalkoxy group, R3 represents a fluorine atom, a chlorine atom or a bromine atom, R4 represents a hydrogen atom; C1-4 alkyl group optionally substituted with a methoxy group, one or more of halogen atom(s), a cyano group, a methylthio group, a methylsulfinyl group or a
methylsulfonyl group; C3-4 alkenyl; C3-4 alkynyl; or C3-5 cycloalkyl, R5 represents a hydrogen atom or a methyl group, R6 represents a hydrogen atom, a fluorine atom or a
chlorine atom, R7 represents a hydrogen atom, a fluorine atom or a chlorine atom;
and the like.
Active ingredients of the acaricides include, for example, acequinocyl, amitraz, benzoximate, bifenazate, bromopropylate, chinomethionat , chlorobenzilate, CPCBS
(chlorfenson) , clofentezine, cyflumetofen, kelthane
(dicofol), etoxazole, fenbutatin oxide, fenothiocarb, fenpyroximate, fluacrypyrim, fluproxyfen, hexythiazox, propargite (BPPS) , polynactins, pyridaben, Pyrimidifen, tebufenpyrad, tetradifon, spirodiclofen, amidoflumet and the like.
Active ingredients of the nematocides include, for example, DCIP, fosthiazate, levamisol, methyisothiocyanate, morantel tartarate and the like.
Active ingredients of the fungicides include, for example, acibenzolar-S-methyl, amobam, ampropylfos,
anilazine, azoxystrobin, benalaxyl, benodanil, benomyl, benthiavalicarb, benthiazole, bethoxazin, bitertanol, blasticidin-S, Bordeaux' mixture, boscalid, bromuconazole, buthiobate, Calcium hypochlorite, Calcium polysulfide, captan, carbendazol, carboxin, carpropamid, chlobenthiazone, chloroneb, chloropicrin, chlorothalonil (TPN) ,
chlorthiophos, Cinnamaldehyde, cloz.ylacon, CNA (2,6-
Dichloro-4-nitroaniline) , Copper hydroxide, Copper sulfate, cyazofamid, cyfluphenamid, cymoxanil, cyproconazole,
cyprodinil, cyprofuram, dazomet, debacarb, 'dichlofluanid, D-D ( 1, 3-Dichloropropene) , diclocymet, diclomezine,
diethofencarb, difenoconazole, diflumetorim, dimefluazole, dimethirimol, dimethomorph, diniconazole-M, dinocap,
edifenphos, epoxiconazole, nickel dimethyldithiocarbamate, etaconazole, ethaboxam, ethirimol, etridiazole, famoxadone, fenamidone, fenarimol, fenbuconazole, Fendazosulam,
fenhexamid, fenoxanil, fenpiclonil, fenpropidin,
fenpropimorph, fentiazon,' fentin hydroxide, ferimzone, fluazinam, fludioxonil, flumetover, flumorph, fluoroimide, fluotrimazole, fluoxastrobin, . fluquinconazole, flusilazole, flusulfamide, flutolanil, flutriafol, fosetyl-Al, fthalide, fuberidazole, furalaxyl, furametpyr, furcarbanil,
furconazole-cis, hexaconazole, hymexazol, IBP, imazalil, imibenconazole, iminoctadine-albesilate, iminoctadine- triacetate, iodocarb, ipconazole, iprodione, iprovalicarb, isoprothiolane, kasugamycin, kresoxim-methyl, mancozeb, maneb, mepanipyrim, mepronil, metalaxyl, metalaxyl-M, metam-sodium, methasulfocarb, Methyl bromide, metconazole, methfuroxam, metominostrobin, metrafenone, metsulfovax, mildiomycin, milneb, myclobutanil, myclozolin, nabam, orysastrobin, ofurace, oxadixyl, oxolinic acid,
oxpoconazole, oxycarboxin, oxytetracycline, pefurazoate, penconazole, pencycuron, picoxystrobin, polycarbamate, polyoxin, Potassium hydrogen carbonate, probenazole,
prochloraz, procymidone, propamocarb-hydrochloride,
propiconaole, propineb, proquinazid, prothiocarb,
prothioconazole, pyracarbolid, pyraclostrobin, pyrazophos, pyributicarb, pyrifenox, pyrimethanil, pyroquilon,
quinoxyfen, quintozene (PCNB) , silthiopham, simeconazole, sipconazole, Sodium bibarbonate, sodium hypochlorite, spiroxamine, ((E)-2[2-(2, 5-dimethylphenoxymethyl) phenyl] -2- methoxyimino-N-methylacetamide) , streptomycin, Sulfur, tebuconazole, tecloftalam, tetraconazole, thiabendazole, thiadinil, thiram (TMTD) , thifluzamide, thiophanate-methyl, tolclofos-methyl, TPN, triadimefon, triadimenol, triazoxide, triclamide, tricyclazole, tridemorph, triflumizole,
trifloxystrobin, triforine, triticonazole, validamycin, vinclozolin, viniconazole, zineb, ziram and zoxamide.
Active ingredients of the herbicides and plant growth regulators include, for example, Abscisic acid, acetochlor, acifluorfen-sodium, alachlor, alloxydim, ametryn,
amicarbazone, amidosulfuron, aminoethoxyvinylglycine, aminopyralid, AC94, 377, amiprofos-methyl, ancymidol, asulam, atrazine, aviglycine, azimsulfuron, beflubutamid, benfluralin, benfuresate, bensulfuron-methyl, bensulide (SAP) , bentazone, benthiocarb, benzamizole, benzfendizone, benzobicyclon, benzofenap, benzyl adenine,
benzylaminopufine, bialaphos, bifenox, Brassinolide, bromacil, bromobutide, butachlor, butafenacil, butamifos, butylate, cafenstrole, Calcium carbonate, Calcium peroxide, carbaryl, chlomethoxynil, chloridazon, chlorimuron-ethyl, chlorphthalim, chlorpropham, chlorsulfuron, chlorthal- dimethyl, chlorthiamid (DCBN), choline chloride, cinidon- ethyT, cinmethylin, cinosulfuron, clethodim, clomeprop, cloxyfonac-sodium, chlormequat chloride, 4-CPA (4- chlorophenoxyacetic acid) , cliprop, clofencet, cumyluron, cyanazine, cyclanilide, cyclosulfamron, cyhalofop-butyl,
2, 4-Dichlorophenoxyacetic acid salts, dichlorprop (2,4-DP), daimuron, dalapon (DPA) , dimethenamid-P, daminozide, dazomet, n-Decyl alcohol, dicamba-sodium (MDBA),
dichlobenil (DBN), diflufenican, dikegulac, dimepiperate, dimethametryn, dimethenamid, diquat, dithiopyr, diuron, endothal, epocholeone, esprocarb, ethephon, ethidimuron, ethoxysulfuron, ethychlozate, etobenzanid, fenarimol, fenoxaprop-ethyl, fentrazamide, flazasulfuron, florasulam, fluazifop-butyl, fluazolate, flucarbazone, flufenacet, flufenpyr, flumetralin) , flumioxazin, flupropanate-sodium, flupyrsulfuron-methyl-sodium, flurprimidol, fluthiacet- methyl, foramsulfuron, forchlorfenuron, formesafen,
gibberellin, glufosinate, glyphosate, halosulfuron-methyl, hexazinone, imazamox, imazapic, imazapyr, imazaquin,
imazosulfuron, inabenfide, Indole acetic acid (IAA), Indole butyric acid, iodosulfuron, ioxynil-octanoate, isouron, isoxachlortole, isoxadifen, karbutilate, lactofen, lenacil, linuron, LGC-42153, Maleic hydrazide, mecoprop (MCPP) , 2- Methyl-4-chlorophenoxyacetic acid salts, MCPA-thioethyl, 2- Methyl-4-chlorophenoxybutanoic acid ethyl ester, mefenacet, mefluidide, mepiquat, mesosulfuron, mesotrione, methyl daimuron, metamifop, metolachlor, metribuzin, metsulfuron- methyl, molinate, naphthylacetic acid, 1- naphthaleneacetamide, naproanilide, napropamide, n-decyl alcohol, nicosulfuron, n-phenylphthalamic acid, orbencarb, oxadiazon, oxaziclomefone, oxine-sulfate, paclobutrazol, paraquat, Pelargonic acid, pendimethalin, penoxsulam, pentoxazone, pethoxamide, phenmedipham, picloram,
picolinafen, piperonyl butoxide, piperophos, pretilachlor, primisulfuron-methyl, procarbazone, prodiamine, profluazol, profoxydim, prohexadione-calcium, prohydrojasmon, prometryn, propanil, propoxycarbazone, propyzamide, pyraclonil,
pyraflufen-ethyl, pyrazolate, pyrazosulfuron-ethyl,
pyrazoxyfen, pyribenzoxim, pyributicarb, pyridafol,
pyridate, pyriftalid, pyriminobac-methyl, pyrithiobac, quiclorac, quinoclamine, quizalofop-ethyl, rimsulfuron, sethoxydim, siduron, simazine, simetryn, Sodium chlorate, ^ sulfosulfuron, swep (MCC) , tebuthiuron, tepraloxydim, terbacil, terbucarb (MBPMC) , thenylchlor, thiazafluron, thidiazuron, thifensulfuron-methyl, triaziflam, tribufos, triclopyr, tridiphane, trifloxysulfuron, trifluralin, trinexapac-ethyl, tritosulfuron, uniconazole-P and vemolate (PPTC) .
The pesticide of the present invention can also be used further in admixture with a synergist such as
piperonyl butoxide, sesamex, N- (2-ethylhexyl) -8 , 9, 10- trinό,rborn-5-en-2, 3-dicarboxyimide (MGK 264), WARF- antiresistant and diethylmaleate, and furthermore, may be used in admixture with a safener such as benoxacor,
cloquintocet-mexyl, cyometrinil, daimuron, dichlormid, fenchlorazole-ethyl, fenclorim, flurazole, fluxofenim, furilazole, mefenpyr-diethyl, MG191, naphthalic anhydride and oxabetrinil.
Examples of the pest against which the compound (I) or a salt thereof has an activity include arthropods such as insect pests, acarine pests and the like, and nematode pests. Specific examples are listed below:
Hemiptera: Delphacidae such as Laodelphax striatellus, Nilaparvata lugens, Sogatella furcifera and the like; Deltocephalidae such as Nephotettix cincticeps, Nephotettix virescens and the like; Aphididae such as Aphis gossypii, Myzus persicae, Brevicoryne brassicae, Macrosiphum euphorbiae, Aulacorthum solani, Rhopalosiphum padi, Toxoptera citricidus and the like; Pentatomidae such as Nezara antennata, Riptortus clavetus, Leptocorisa chinensis, Eysarcoris parvus, Halyomorpha mista and the like; Aleyrodidae such as Trialeurodes vaporariorum, Bemisia argentifolii and the like; Coccidae such as Aonidiella aurantii, Comstockaspis perniciosa, Unaspis citri, Ceroplastes rubens, Icerya purchasi and the like; Tingidae, Psyllidae, and the like.
NLepidoptera : Pyralidae such as Chilo suppressalis, Tryporyza incertulas, Cnaphalocrocis medinalis, Notarcha derogata, Plodia interpunctella, Ostrinia furnacalis,
Hellula undalis, Pediasia teterrellus and the like;
Noctuidae such as Spodoptera litura, Spodoptera exigua, Pseudaletia separata, Mamestra brassicae, Agrotis ipsilon, Plusia nigrisigna, Thoricoplusia spp. , Heliothis spp., Helicoverpa spp., and the like; Pieridae such as Pieris rapae and the like; Tortricidae such as Adoxophyes spp., Grapholita molesta, Leguminivora glycinivorella,
Matsumuraeses azukivora, Adoxophyes orana fasciata,
Adoxophyes sp., Homona magnanima, Archips fuscocupreanus, Cydia pomonella and the like; Gracillariidae such as
Caloptilia theivora, Phyllonorycter ringoneella and the like; Carposinidae such as Carposina niponensis and the like; Lyonetiidae such as Lyonetia spp. and the like;
Lymantriidae such as Lymantria spp., Euproctis spp., and the like; Yponomeutidae such as Plutella xylostella and the like; Gelechiidae such as Pectinophora gossypiella,
Phthorimaea operculella and the like; Arctiidae such as Hyphantria cunea and the like; Tineidae such as Tinea translucens, Tineola bisselliella and the like.
Thysanoptera : Thripidae such as Frankliniella
occidentalis, Thrips parmi, Scirtothrips dorsalis, Thrips tabaci, Frankliniella intonsa and the like.
'iDiptera: Musca domestica, Culex popiens pallens,
Tabanus trigonus, Hylemya antiqua, Hylemya platura,
Anopheles sinensis, Agromyza oryzae, Hydrellia griseola, Chlorops oryzae, Dacus cucurbitae, Ceratitis capitata,
Liriomyza trifolii and the like.
Coleoptera: Epilachna vigintioctopunctata, Aulacophora femoralis, Phyllotreta striolata, Oulema oryzae,
Echinocnemus squameus, Lissorhoptrus oryzophilus,
Anthonomus grandis, Callosobruchus chinensis, Sphenophorus venatus, Popillia japonica, Anomala cuprea, Diabrotica spp., Leptinotarsa decemlineata, Agriotes spp., Lasioderma
serricorne, Anthrenus verbasci, Tribolium castaneum, Lyctus brunneus, Anoplophora malasiaca, Tomicus piniperda and the like. Orthoptera: Locusta migratoria, Gryllotalpa africana,
Oxya yezoensis, Oxya japonica and the like.
Hymenoptera: Athalia rosae, Acromyrmex spp.,
Solenopsis spp. and the like.
Nematode: Aphelenchoides besseyi, Nothotylenchus acris and the like.
Blattodea: Blattella germanica, Periplaneta fuliginosa,
Periplaneta americana, Periplaneta brunnea,- Blatta
orientalis and the like.
Acarina: Tetranychidae such as Tetranychus urticae,
Panonychus citri, Oligonychus spp., and the like;
Eriophyidae such as Aculops pelekassi and the like;
Tarsonemidae such as Polyphagotarsonemus latus and the like; Tenuipalpidae; Tuckerellidae; Ixodidae such as
Haemaphysalis longicornis, Haemaphysalis flava, Dermacentor taiwanicus, Ixodes ovatus, Ixodes persulcatus, Boophilus microplus, Rhipicephalus sanguineus and the like; Acaridae such as Tyrophagus putrescentiae and the like;
Epidermoptidae such as Dermatophagoides farinae,
Dermatophagoides ptrenyssnus and the like; Cheyletidae such as Cheyletus eruditus, Cheyletus malaccensis, Cheyletus moorei and the like; and Dermanyssidae and the like.
The method for controlling pests of the present invention is carried out by applying the compound (I) or a salt thereof to pests directly, or habitats of pests. In the method for controlling pests of the present invention, the compound (I) or a salt thereof can be used as it is, but usually, a preparation of the compound (I) or a salt thereof, or an aqueous dilution of the preparation is used.
Examples of the habitat of pests in the present invention include paddy fields, dry rice fields, fields, tee plantations, orchards, uncultivated fields, houses, seedling growing trays, nursery boxes, seedling growing medias, seedling growing mats, water culture mediums for hydroponic farm, and the like.
xAs a method for application, for example, a spray treatment, a soil treatment, a seed treatment and a
hydroponic solution treatment are exemplified.
The spray treatment in the present invention is a method of treatment for expressing a controlling effect against pests by treating plant surface or pest itself with an active ingredient (the compound (I) or a salt thereof), specifically for example, foliage application, spraying to tree trunk and the like. The soil treatment is a method of treatment for protecting crops from damages by pests, by treating soils, growing medias, irrigation solutions or the like with an active ingredient in order to penetrate and translocate from the root portion and the like into the plant interior of a crop to be protected from damages such as feeding and the like by pests, and specifically, for example, a planting hole treatment (planting hole spraying, soil-incorporation after planting hole treatment), a plant foot treatment (plant foot spraying, plant foot soil- incorporation, plant foot irrigation, plant foot
treatment at latter half of raising seeding period) , planting furrow treatment (planting furrow spraying, planting furrow soil-incorporation) , planting row
treatment (planting row spraying, planting row soil- incorporation, planting row spraying at growing period) , planting row treatment at sowing (planting row spraying at sowing, planting row soil-incorporation at sowing) , overall treatment (overall spraying, overall soil- incorporation) , other spray treatment (foliar granule spraying at growing period, spraying under tree crown or around main stem, soil surface spraying, soil surface incorporation, sowing hole spraying, spraying on the
ribbing ground, inter-plant spraying) , other irrigation treatment (irrigation into soil, irrigation during raising seeding, injection treatment of pesticide solution,
irrigation on plant foot, pesticide solution drip
irrigation, chemigation) , nursery box treatment (nursery box spraying, nursery box irrigation) , nursery tray
treatment (nursery tray spraying, nursery tray irrigation) , nursery bed treatment (nursery bed spraying, nursery bed irrigation, nursery bed spraying in paddy field, immersion of nursery plant) , seed bed soil-incorporation treatment (seed bed soil-incorporation, seed bed soil-incorporation before sowing) , other treatment (growing media
incorporation, plowing, surface soil-incorporation, soil incorporation "into rain dropping, planting spot treatment, flower cluster granule spraying, paste fertilizer mixing) , and the like are exemplified. The seed treatment is a method of treatment for expressing a controlling effect against pests by treating seeds, seed tubers, bulbs or the like of a crop to be protected from damages such as feeding and the like by pests directly, or neighborhood thereof, with an active ingredient, and specifically, for example, blowing treatment, painting treatment, immersion treatment, impregnation treatment, application treatment, film coating and a pellet coating treatment are exemplified. The hydroponic solution treatment is a method of treatment for protecting crops from damages by pests, by treating hydroponic solution or the like with an active ingredient in order to penetrate and translocate from the root portion and the like into the plant interior of a crop to be protected from damages such as feeding and the like by pests, and specifically, for example, hydroponic solution incorporation, hydroponic solution mixing, and the like are exemplified. The amount of application of the compound (I) or a salt thereof in the method for controlling pests in the present invention can be changed depending on the
application time, application site, application method and the like, but in general, it is at a rate of about 0.3 to 3000 g, preferably at a rate of about 50 to 3000 g as an amount of the active ingredient (the compound (I)) per hectare. In addition, when the pesticide of the present invention is a wettable powder or the like, it may be diluted with water to use so that the final concentration o.f active ingredient comes to the range of about 0.1 to 1,00O1 ppm, preferably about 10 to 500 ppm.
Hereinafter, the present invention will be further illustrated by the following Production Examples, Examples, Preparation Examples, Test Examples and the like, however, the present invention is not limited to these examples.
The elution in the column chromatography for
Production Examples, Examples and Reference Production Examples was carried out under the observation by TLC (Thin Layer Chromatography) . In the TLC observation, kieselgel 60F254 manufactured by Merck & Co., Inc. was used as TLC plate; the solvent used as an elution solvent in column chromatography was used as developing solvent; and a UV detector was used for detection. Kieselgel 60 (70 to 230 meshes) manufactured by Merck & Co., Inc. was used as silica gel for column chromatography. As a medium pressure preparative high performance liquid chromatography, Ultra pack manufactured by Yamazen, Co., Ltd. (filler: silica gel) has been used. When a mixed solvent was used as developing solvent, the numeric value in parentheses shows a mixing ratio" of solvents by volume. NMR spectra were proton NMR, and were determined with JEOL AL-400 (400MHz) spectrometer and Bruker AVANCE 400 (400MHz) spectrometer using tetramethylsilane as internal standard. All delta values were shown in ppm. The measurement temperature is 25°C unless otherwise mentioned, and the measurement temperature has been indicated for the rest.
Furthermore, the abbreviations used in the following Production Examples and Examples have the following
meanings:
Me: methyl group, Et: ethyl group, Ph: phenyl group, Pr-n (or n-Pr) : n-propyl, Pr-i (or i-Pr or 1Pr) : isopropyl, Pr-cyclo (or cyclo-Pr) : cyclopropyl, Bu-n (or n-Bu) : n- butyl, Bu-i (or i-Bu) : isobutyl, Bu-s (or s-Bu) : sec-butyl, Bu-t (or t-Bu) : tert-butyl, s: singlet, br: broad, brs; broad singlet, d: doublet, t: triplet, q: quartet, qu :
quintet (quintet line), sep: septet (septet line), m:
multiplet, dd: double doublet, dt : double triplet, J:
coupling constant, Hz: hertz, %: % by weight. In addition, room temperature means about 15 to 25°C. First, Production Examples and Examples of the
compound (I) will be shown.
Example 1
To a, solution of 1.00 g of 1- (2, 6-difluorobenzoyl) -3- [2-fluoro-4- (trifluoromethylthio) phenyl] urea in 9 ml of 1- methyl-2-pyrrolidone was added 0.15 g of sodium hydride (content; 60% by weight) at 3°C under ice-cooling, and the mixture was stirred for 30 minutes. A solution of 0.57 ml of chloromethyl methyl ether in 1 ml of l-methyl-2- pyrrolidone, and 0.15 g of sodium hydride (content; 60%) were sequentially added to the mixture at 40C, and the resulting mixture was stirred at 5°C for 2 hours. To the reaction mixture was added a mixture of 10 ml of an aqueous saturated ammonium chloride solution and 5 ml of water at 2 to 25°C under ice-cooling, followed by extraction with 10 ml of ethyl acetate three times. The organic layer was washed with 10 ml of an aqueous saturated sodium chloride solution three times, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The resulting residue was purified by silica gel column
chromatography (ethyl acetate : chloroform: hexane = 1:1:4), and further purified by medium pressure preparative high performance liquid chromatography (ethyl
acetate: chloroform: hexane = 15:15:70) to obtain 0.51 g of 1, 3-bis (methoxymethyl) -1- (2, 6-difluorobenzoyl) -3- [2-fluoro- 4- (trifluoromethylthio) phenyl] urea (hereinafter, referred to as present compound (I)) .
Present compound (1)
Figure imgf000210_0001
1H-NMR (CDCl3 )δ[ppm] : 3.37 (3H, s) , 3.54 (3H, s) , 4.81 (2H, s) , 5.11-5.14 (2H, br) , β.83-6.85 (2H, m) , 7.26-7.48 (4H, m)
Examples 2 to 20
•According to the same manner as that of Example 1, the following compounds were produced.
1, 3-Bis (ethoxymethyl) -1- (2, 6-difluorobenzoyl) -3- [2- fluoro-4- (trifluoromethylthio) phenyl] urea (hereinafter, referred to as present compound (2))
Present compound (2)
Figure imgf000210_0002
1H-NMR (CDCl3 )δ[ppm] : 1.10(3H, t), 1.24(3H, t), 3.59(2H, br), 3.79(2H,br), 4.84(2H, br) , 5.17(2H, br) , 6.83(2H, br) , 7.30-7.34 (IH, m) , 7.42-7.48 (3H, m)
1, 3-Bis (methoxymethyl) -1- (2-chloro-6-fluorobenzoyl ) -3- [2-fluoro-4- (trifluoromethylthio) phenyl] urea (hereinafter, referred to as present compound (3) )
Present compound (3)
Figure imgf000211_0001
1H-NMR (CDCl3 )δ[ppm] : 3.34 (3H, brs), 3.56 (3H, brs) , 4.60- 5.30 (4H, brm) , 6.80-7.00 (IH, br) , 7.10-7.30 (2H, brm) , 7.44-7.52 (3H, m)
1, 3-Bis (methoxymethyl) -1- (2, 6-dichlorobenzoyl) -3- [2- fluoro-4- (trifluoromethylthio) phenyl] urea (hereinafter, referred to as present compound (4))
Present compound (4)
1H-NMR (CDCl3 )δ[ppm] : 3.31(3H, s), 3.57(3H, s), 4.73(2H, br) , 5.0-5.2(2H, br) , 7.24-7.27 (3H, br) , 7.45-7.48 (2H, m) , 7.60-7.64 (IH, m)
1, 3-Bis (methylthiomethyl) -1- (2, 6-difluorobenzoyl) -3- [2-fluoro-4- (trifluoromethylthio) phenyl] urea (hereinafter, referred to as present compound (5))
Present compound (5)
1H-NMR (CDCl3 )δ[ppm] : 2.15-2.,20 (3H, brs), 2.23 (3H, s) , 4.50-5.10 (4H, brm) , 6.85-6.99 (2H, m) , 7.33-7.52 (4H, m) 1, 3-Bis (methoxymethyl) -1- (2, 6-dif luorobenzoyl) -3- (4- chloro-2-fluorophenyl) urea (hereinafter, referred to as present compound (6) )
Present compound (6)
Figure imgf000212_0002
1H-NMR (CDCl3 ) δ [ppm] : 3.37(3H, s) , 3.51(3H, s) , 4.8 (2H, br) , 5.1(2H, br) , 6.85-6.89 (2H, m) , 7.12-7.20(2H, m) , 7.31-
7.38 (2H, m)
1, 3-Bis (methoxymethyl) -1- (2, 6-difluorobenzoyl) -3- (4- chlorophenyl) urea (hereinafter, referred to as present compound (7 ) )
Present compound (7)
Figure imgf000212_0003
1H-NMR (CDCl3 )δ[ppm] : 3.35(3H, s), 3.45(3H, s), 4.8(2H, br) , 5.1(2H, br) , 6.88-6.92 (2H, m) , 7.21-7.23V(2H, m) , 7.33- 7.37 (3H, m) .
1, 3-Bis (methoxymethyl) -1- (2, 6-difluorobenzoyl) -3- (3, 5- dichloro-2, 4-difluorophenyl) urea (hereinafter, referred to as present compound (8))
Present compound (8)
Figure imgf000213_0001
1H-NMR (CDCl3 )δ[ppm] : 3.35(3H, s), 3.53(3H, s), 4.8(2H, br) , 5.1(2H, br) , 6.89-6.92 (2H, br) , 7.35-7.41 (2H, m)
1, 3-Bis (methoxymethyl) -1- (2, 6-difluorobenzoyl) -3- [4- (2-chloro-4-trifluoromethylphenoxy) -2-fluorophenyl] urea (hereinafter, referred to as present compound (9))
Present compound (9)
Figure imgf000213_0002
1H-NMR (CDCl3 )δ[ppm] : 3.39(3H, s) , 3.53(3H, s) , 4.8 (2H, br) , 5.0(2H, br) , 6.75-6.79 (2H, m) , 6.8 (2H, m) , 7.08-7.10 (1H, m) , 7.35-7.38 (2H, m) , 7.48-7.50 ( IH, m) , 7.76(1H, m)
1, 3-Bis (methoxymethyl) -1- (2, 6-dif luorobenzoyl) -3- [2- fluoro-4-(l,l,2, 2-tetrafluoroethylthio) phenyl] urea
(hereinafter, referred to as present compound (10) )
Present compound (10)
Figure imgf000214_0001
1H-NMR (CDCl3 )δ[ppm] : 3.37(3H, s), 3.54(3H, s) , 4.82(2H, br), 5.0-5.3(2H, br) , 5.65-5.92 ( IH, m) , 6.8-6.9(2H, m) , 7.31-7.35 (IH, m) , 7.43-7.48 ( 3H, m)
1, 3-Bis (methoxymethyl) -1- (2, 6-difluorobenzoyl) -3- (2- fluoro-4-methylthiophenyl) urea (hereinafter, referred to as present compound (H))
Present compound (11)
Figure imgf000214_0002
1H-NMR (CDCl3 )δ[ppm] : 2.48 (3H, s) , 3.38 (3H, s) , 3.49 (3H, s) , 4.83 (2H, s) , 5.06 (2H, s) , 6.82-6.91 (2H, m) , 6.96- 7.04 (2H, m) , 7.19-7.39 (2H, m)
1, 3-Bis (methoxymethyl) -1- (2-chloro-6-fluorobenzoyl) -3- (2-fluoro-4-methylthiophenyl) urea (hereinafter, referred to as present compound (12))
Present compound (12)
Figure imgf000215_0001
1H-NMR (DMSO-de, measuring temperature : 8O0C) δ [ppm] : 2.50 (3H, s), 3.22 (3H, s), 3.34 (3H, s), 4.73 (2H, s), 5.01 (2H, s), 7.09-7.14 (IH, m) , 7.17-7.36 (4H, m) , 7.44-7.53 (IH, m)
1, 3-Bis (methoxymethyl) -1- (2, β-difluorobenzoyl) -3- (2- fluoro-4-ethylthiophenyl) urea (hereinafter, referred to as present compound (13))
Present compound (13)
Figure imgf000215_0002
1H-NMR (CDCl3 )δ [ppm] : 1.33 (3H, t, J = 7.4 Hz), 2.95 (2H, q, J = 7.4 Hz), 3.38 (3H, s) , 3.50 (3H, br s), 4.83 (2H, s), 5.06 (2H, br s), 6.79-6.92 (2H, m) , 7.01-7.10 (2H, m) ,
7.19-7.39 (2H, m)
1, 3-Bis (methoxymethyl) -1- (2, 6-difluorobenzoyl) -3- [2- fluoro-4- (1,1,2,2, 2-pentafluoroethyIthio) phenyl] urea
(hereinafter, referred to as present compound (14))
Present compound (14)
Figure imgf000216_0001
1H-NMR (CDCl3 )δ[ppm] : 3.37 (3H, s) , 3.54 (3H, br s) , 4.82 (2H, s) , 5.13 '(2H, br s) , 6.76-6.91 (2H, m) , 7.28-7.38 (IH, m) , 7.40-7.51 (3H, m)
1, 3-Bis (methoxymethyl) -1- (2, 6-difluorobenzoyl) -3- [2- fluoro-4- (1,1,2,2,3,3, 3-heptafluoropropylthio) phenyl] urea (hereinafter, referred to as present compound (15))
Present compound (15)
Figure imgf000216_0002
1H-NMR (CDCl3 )δ[ppm] : 3.37 (3H, s) , 3.54 (3H, br s) , 4.82 (2H, s) , 5.13 (2H, br s) , 6.74-6.90 (2H, m) , 7.28-7.38 (IH, m) , 7.41-7.52 (3H, m)
1, 3-Bis (methoxymethyl) -1- (2-chloro-6-fluorobenzoyl) -3- (2-fluoro-4-ethylthiophenyl) urea (hereinafter, referred to as present compound (16) )
Present compound (16)
Figure imgf000217_0001
1H-NMR (DMSOd6, measuring temperature : 80°C) δ [ppm] : 1.27 (3H, t, J = 7.3 Hz) , 3.01 (2H, q, J = 7.3 Hz) , 3.23 (3H, s) ,
3.36 (3H, s) , 4.73 (2H, br s) , 5.03 (2H, s) , 7.12-7.17 (IH, m) , 7.19-7.25 (2H, m) , 7.27-7.34 (2H, m) , 7.43-7.51 (IH, m) 1, 3-Bis (methoxymethyl) -1- (2, 6-difluorobenzoyl) -3- [2- fluoro-4- (1,1,2, 2-tetrafluoroethoxy) phenyl] urea
(hereinafter, referred to as present compound (17))
Present compound (17)
Figure imgf000217_0002
1H-NMR (DMSO-d6, measuring temperature : 8O0C) δ [ppm] : 3.23 (3H, s), 3.36 (3H, s), 4.79 (2H, s), 5.04 (2H, s), 6.71 (IH, tt, J = 51.9, 3.1 Hz), 7.05-7.13 (2H, m) , 7.14-7.20 (IH, m) , 7.26-7.32 (IH, m) , 7.41-7.48 (IH, m) , 7.49-7.58 (IH, m)
1, 3-Bis (methoxymethyl) -1- (2, 6-difluorobenzoyl) -3- (2- fluoro-4-trifluoromethylphenyl) urea (hereinafter, referred to as present compound (18))
Present compound (18)
Figure imgf000218_0001
1H-NMR (CDCl3 )δ[ppm] : 3.38 (3H, s) , 3.53(3H, s) , 4.83(2H, br) , 5.14 (2H, br) , 6.83-6.87 (2H, m) , 7.30-7.37 ( IH, m) ,
7.41-7.43(2H, m) , 7.53(1H, m)
1, 3-Bis (methoxymethyl) -1- (2-chloro-6-fluorobenzoyl) -3- [2-fluoro-4- (1,1,2, 2-tetrafluoroethylthio) phenyl] urea
(hereinafter, referred to as present compound (19))
Present compound (19)
Figure imgf000218_0002
1H-NMR (DMSO-de, measuring temperature : 8O0C) δ [ppm] : 3.23
(3H, s) , 3.37 (3H, s) , 4.77 (2H, br s) , 5.09 (2H, s) , 6.65 (IH, tt, J = 52.5, 3.7 Hz) , 7.21 (IH, t, J = 8.8 Hz) , 7.32 (IH, d, J = 8.2 Hz) , 7.45-7.52 (IH, m) , 7.52-7.59 (2H, m) , 7.60-7.65 (IH, m)
1, 3-Bis (methoxymethyl) -1- (2, 6-difluorobenzoyl) -3- (4- trifluoromethoxyphenyl) urea (hereinafter, referred to as present compound (20))
Present compound (20)
Figure imgf000219_0001
1H-NMR (CDCl3 )δ[ppm] : 3.33(3H, s) , 3.48(3H, s), 4.85(2H, br) , 5.09(2H, t>r) , 6.86-6.90 (2H, m) , 7.20-7.36 (5H, m)
Example 21
A solution of 1.00 g of 1- (2, 6-difluorobenzoyl) -3- [2- fluoro-4- (trifluoromethylthio) phenyl] -1-methylurea and 0.45 ml of chloromethyl methyl ether in 10 ml of l-methyl-2- pyrrolidone was ice-cooled, 0.12 g of sodium hydride
(content; 60% by weight) was added to the solution at 3°C, and the mixture was stirred at 5°C for 1 hour. To the reaction mixture was added a mixture of 10 ml of an aqueous saturated ammonium chloride solution and 5 ml of water at 2 to 25°C, followed by extraction with 10 ml of ethyl acetate three times. The organic layer was washed with 10 ml of an aqueous saturated sodium chloride solution three times, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The resulting residue was purified by medium pressure preparative high performance liquid chromatography (ethyl acetate : chloroform: hexane = 15:15:70) to obtain 0.73 g of 1- (2, 6-difluorobenzoyl) -3- [2-fluoro-4- (trifluoromethylthio) phenyl] -3- (methoxymethyl) -1-methylurea (hereinafter, referred to as present compound (21)). Present compound (21)
Figure imgf000220_0001
1H-NMR (CDCl3 )δ[ppm] : 3.10 (3H, s), 3.52 (3H, brs), 5.12 (2H, br), 6.86-6.88 (2H, m) , 7.30-7.49 (4H, m)
Production Example 1
A solution 1.00 g of 1- (2, 6-difluorobenzoyl) -3- [2- fluoro-4- (trifluoromethylthio) phenyl] urea in 10 ml of 1- methyl-2-pyrrolidone was ice-cooled, 0.11 g of sodium hydri'de (content; 60% by weight) was added to the solution at 3°C, and the mixture was stirred for 30 minutes. A solution of 0.50 ml of 2- (trimethylsilyl) ethoxymethyl chloride in 1 ml of l-methyl-2-pyrrolidone was added dropwise to the mixture at 4°C, and the resulting mixture was stirred at 5°C for 30 minutes. To the reaction mixture was added a mixture of 10 ml of an aqueous saturated ammonium chloride solution and 5 ml of water at 2 to 25°C, followed by extraction with 10 ml of ethyl acetate three times. The organic layer was washed with 10 ml of an aqueous saturated sodium chloride solution three times, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (ethyl acetate : hexane = 1:5) to obtain 1.26 g of 1- (2, β-difluorobenzoyl) -3- [2- fluoro-4- (trifluoromethylthio) phenyl] -1- [2- (trimethylsilyl) ethoxymethyl] urea.
Figure imgf000221_0001
1 H-NMR ( CDC l3 ) δ [ ppm] : 0 . 03 ( 9H , s ) , 0 . 8 9 - 0 . 93 ( 2H , m) ,
3.57-3.61 (2H, m) , 5.28 (2H, s) , 7.00-7.05 (2H, m) , 7.43- 7.49 (3H, m) , 8.35-8.39 (IH, m)
Production Example 2
-A solution of 1.02 g of 1- (2, 6-difluorobenzoyl) -3- [2- fluoro-4- (trifluoromethylthio) phenyl] -1- [2-
(trimethylsilyl) ethoxymethyl] urea in 10 ml of l-methyl-2- pyrrolidone was ice-cooled, 80 mg of sodium hydride
(content; 60% by weight) 'was added to the solution at 3°C, the mixture was stirred for 30 minutes, 0.19 ml of
chloromethyl ethyl ether was added dropwise to the mixture at 4°C, and the resulting mixture was stirred at 5°C for 3 hours. To the reaction mixture was added a mixture of 10 ml of an aqueous saturated ammonium chloride solution and 5 ml of water at 2 to 25°C, followed by extraction with 10 ml of ethyl acetate three times. The organic layer was washed with 10 ml of an aqueous saturated sodium chloride solution three times, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (ethyl v acetate : hexane = 1:5), and was further purified by medium pressure preparative high performance liquid chromatography (ethyl acetate: hexane = 15:85) to obtain 0.41 g of l-(2,6- difluorobenzoyl) -3-ethoxymethyl-3- [2-fluoro-4- ( trifluoromethythio) phenyl] -1- [2- (trimethylsilyl) ethoxymethyl] urea .
Figure imgf000222_0001
1H-NMR (CDCl3 )δ[ppm] : 0.03 (9H, s) , 0.80-0.90 (2H, m) ,
1.20-1.40 (3H, m) , 3.50-3.75 (2H, br) , 3.75-3.95 (2H, br) , 4.80-5.00 (2H, br) , 5.00-5.40 (2H, br) , 6.80-7.00 (2H, br) , 7.30-7.60 (4H, m)
Example 22
To a solution of 0.41 g of 1- (2 , 6-difluorobenzoyl) -3- ethoxymethyl-3- [2-fluoro-4- (trifluoromethylthio) phenyl] -1- [2- (trimethylsilyl) ethoxymethyl] urea in 10 ml of
tetrahydrofuran was added 2.2 ml of
tetranormalbutylammonium fluoride (1.0 M-tetrahydrofuran solution) , and the mixture was heated under reflux for 6 hours. The reaction mixture was cooled to room temperature, and added to 10 ml of water, followed by extraction with 10 ml of ethyl acetate. The organic layer was washed with 10 ml of an aqueous saturated sodium chloride solution two times, dried over anhydrous magnesium sulfate, and
concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (ethyl acetate : chloroform: hexane = 1:1:4) to obtain 0.14 g of 1- (2, 6-difluorobenzoyl) -3- (ethoxymethyl) -3- [2-fluoro-4- (trifluoromethylthio) phenyl] urea (hereinafter, referred to as present compound (22)).
Present compound (22)
Figure imgf000223_0001
1H-NMR (CDCl3 )δ[ppm] : 1.18-1.23 (3H, m) , 3.61-3.68 (2H, m) ,
4.90-5.20 (2H, brs), 6.88-6.95 (3H, m) , 7.34-7.40 (2H, m) ,
7.48-7.51 (2H, m)
Examples 23 to 28
According to the same manner as that of Example 22, the following compounds were produced.
1- (2, 6-Difluorobenzoyl) -3- [2-fluoro-4-
(trifluoromethylthio) phenyl] -3- (methylthiomethyl) urea
(hereinafter, referred to as present compound (23) )
Present compound (23)
Figure imgf000224_0001
1H-NMR (DMSO-d6 )δ[ppm] : 2.04 (3H, s), 4.88 (2H, s) , 7.10- 7.14 (2H, m) , 7.47-7.54 (IH, m) , 7.60-7.78 (2H, m) , 7.78- 7.81 (IH, m) , 10.95 (IH, brs)
1- (2, 6-Difluorobenzoyl) -3- ( 4-chloro-2-fluorophenyl) -3- (methoxymethyl) urea (hereinafter, referred to as present compound (24 ))
Present compound (24)
Figure imgf000224_0002
1H-NMR (DMSO-d6 )δ[ppm] : 3.28 (3H, s) , 4.97 (2H, br) , 7.13-
7.18 (2H, m) , 7.35-7.38 ( IH, m) , 7.43-7.60 (3H, m) , 1O.83(1H, br)
1- (2, 6-Difluorobenzoyl) -3- [2-fluoro-4- (2-chloro-4- trifluoromethylphenoxy) phenyl] -3- (methoxymethyl) urea
(hereinafter, referred to as present compound (25))
Present compound (25)
Figure imgf000225_0001
1H-NMR (DMSO-d6 )δ[ppm] : 3.30 (3H, s), 4.96 (2H, brs) , 6.98- 7.01 (IH, m) , 7.13-7.29 (4H, m) , 7.43-7.54 (2H, m) , 7.75- 7.78 (IH, m) , 8.06-8.07 (IH, m) , 10.75 (IH, br)
1- (2, 6-Difluorobenzoyl) -3- (4-chlorophenyl) -3- (methoxymethyl) urea (hereinafter, referred to as present compound (26) )
Present compound (26)
Figure imgf000225_0002
1H-NMR (CDCl3 )δ[ppm] : 3.38(3H, s), 4.95(2H, s), 6.89-
6.94(2H, m) , 7.23-7.25 (2H, m) , 7.35-7.37 ( IH, m) , 7.42-
7.44 (2H, m) , 7.70 (IH, br)
1- (2, 6-Difluorobenzoyl) -3- [2-fluoro-4- (1,1,2,2,2- pentafluoroethylthio) phenyl] -3- (methoxymethyl) urea
(hereinafter, referred to as present compound (27))
Present compound (27)
Figure imgf000226_0001
1H-NMR (DMSO-d6, measuring temperature : 80°C) δ [ppm] : 3.31 (3H, s), 5.01 (2H, s), 7.03-7.10 (2H, m) , 7.43-7.52 (IH, m) , 7.54-7.61 (2H, m) , 7.64-7.69 (IH, m) , 10.64 (IH, br s)
1- (2, 6-Dichlorobenzoyl) -3- (ethoxymethyl) -3- (4- chlorophenyl) urea (hereinafter, referred to as present compound (28 ))
Present compound (28)
Figure imgf000226_0002
1H-NMR (CDCl3 )δ [ppm] : 1.17 (3H, t, J=7.0 Hz) , 3.58 (2H, q,
J=7.0 Hz), 4.98(2H, s), 7.24-7.30 (5H, m) , 7.43-7.45 (2H, m) , 7.60-7.80 (IH, br)
Production Example 3
To a mixture of 20.0 g of 2-fluoro-4- (trifluoromethylthio) aniline, 91.0 g of a 28% sodium
methylate methanol solution and 50 ml of methanol was added a suspension of 4.0 g of paraformaldehyde (content; 90% by weight) in 100 ml of methanol was added, and the mixture was stirred at room temperature for 6 hours. The reaction mixture was poured into 300 ml of ice water, the resulting mixture was filtered, and the resulting white solid was dried under reduced pressure to obtain 21.1 g of 2-fluoro- N-methoxymethyl-4- ( trifluoromethylthio) aniline .
Figure imgf000227_0001
1H-NMR (CDCl3 )δ[ppm] : 3.33 (3H, s), 4.69-4.71 (2H, m) , 5.10-5.25 (IH, br), 6.94-6.96 (IH, m) , 7.26-7.32 (2H, m) Example 29
To a solution of 10.0 g of 2-fluoro-N-methoxymethyl-4- (trifluoromethylthio) aniline in 50 ml of diethyl ether was added dropwise a solution of 7.17 g of 2 , 6-difluorobenzoyl isocyanate in 7 ml of diethyl ether at about -39°C over about 3 minutes, and the temperature was raised to 1°C over 2 hours. The reaction mixture was filtered while washed with 26 ml of hexane, and the resulting white powder was dried under reduced pressure to obtain 13.7 g of l-(2,6- difluorobenzoyl) -3- [2-fluoro-4-
(trifluoromethylthio) phenyl] -3- (methoxymethyl) urea
(hereinafter, referred to as present compound (29) ) .
Present compound (29)
Figure imgf000228_0001
1H-NMR (DMSO-d6 )δ[ppm] : 3.30 (3H, s), 5.02 (2H, s), 7.11- 7.15 (2H, m) , 7.51-7.64 (3H, m) , 7.75-7.78 (IH, m) , 10.97 (IH, brs)
Examples 30 to 41
According to the same manner as that of Example 29, the following compounds were produced.
1- (2, β-Dichlorobenzoyl) -3- [2-fluoro-4- (trif-luoromethylthio) phenyl] -3- (methoxymethyl) urea
(hereinafter, referred to as present compound (30))
Present compound (30)
Figure imgf000228_0002
1H-NMR (DMSO-d6 )δ[ppm] : 3.28(3H, s), 5.02(2H, s), 7.34- 7.42(3H, m) , 7.57-7.59 (2H, m) , 7.71-7.74 ( IH, m) , 1O.98(1H, br)
1- (2-Chloro-β-fluorobenzoyl) -3- [2-fluoro-4- (trifluoromethylthio) phenyl] -3- (methoxymethyl) urea
(hereinafter, referred to as present compound (31) )
Present compound (31)
Figure imgf000229_0001
1H-NMR (DMSO-d6 )δ[ppm] : 3.29(3H, s), 5.02(2H, s), 7.20- 7.24(1H, m) , 7.28-7.30 (IH, m) , 7.40-7.41 ( IH, m) , 7.58- 7.60(2H, m) , 7.73-7.75 ( IH, m) , 11.02(1H, br)
1- (2, 6-Difluorobenzoyl) -3- [2-fluoro-4- (1,1,2,2- tetrafluoroethylthio) phenyl] -3- (methoxymethyl) urea
(hereinafter, referred to as present compound (32) ) Present compound (32)
Figure imgf000229_0002
1H-NMR (DMSO-d6 )δ[ppm] : 3.31 (3H, s) , 5.02 (2H, s) , 6.58-
6.85 (IH, m) , 7.10-7.15 (2H, m) , 7.47-7.58 (3H, m) , 7.67
(IH, m) , 10.91 (IH, brs)
1- (2, 6-Difluorobenzoyl) -3- (2-fluoro-4- methylthiophenyl) -3- (methoxymethyl) urea (hereinafter, referred to as present compound (33) )
Present compound (33)
Figure imgf000230_0001
1H-NMR (CDCl3 )δ[ppm] : 2.51 (3H, s), 3.42 (3H, s), 4.83 (IH, br s), 5.14 (IH, br s), 6.89-6.99 (2H, m) , 7.04-7.14 (2H, m) , 7.18-7.29 (IH, m) , 7.34-7.45 (IH, m) , 7.58 (IH, br s)
1- (2-Chloro-6-fluorobenzoyl) -3- (2-fluoro-4- methylthiophenyl) -3- (methoxymethyl) urea (hereinafter, referred to as present compound (34))
Present compound (34)
Figure imgf000230_0002
1H-NMR (DMSO-d6, measuring temperature : 800C) δ [ppm] : 2.50 (3H, s), 3.29 (3H, s) , 4.93 (2H, s), 7.10-7.14 (IH, m) , 7.16-7.23 (2H, m) , 7.26-7.33 (2H, m) , 7.38-7.46 (IH, m) , 10.38 (IH, s)
1- (2, 6-Difluorobenzoyl) -3- (2-fluoro-4- ethylthiophenyl) -3- (methoxymethyl) urea (hereinafter, referred to as present compound (35))
Present compound (35)
Figure imgf000231_0001
1H-NMR (DMSO-de, measuring temperature : 8O0C) δ [ppm] : 1.27 (3H, t, J = 7.2 Hz), 3.02 (2H, q, J = 7.2 Hz), 3.29 (3H, s), 4.93 (2H, s), 7.04-7.11 (2H, m) , 7.13-7.17 (IH, m) , 7.19- 7.24 (IH, m) , 7.27-7.32 (IH, m) , 7.43-7.52 (IH, m) , 10.38 (IH, s)
1- (2-Chloro-6-fluorobenzoyl) -3- (2-fluoro-4- ethylthiophenyl) -3- (methoxymethyl) urea (hereinafter,
referred to as present compound (36) )
Present compound (36)
Figure imgf000231_0002
1H-NMR (DMSO-de, measuring temperature : 800C) δ [ppm] : 1.28 (3H, t, J = 7.4 Hz), 3.01 (2H, q, J = 7.4 Hz), 3.30 (3H, s) , 4.94 (2H, s), 7.12-7.23 (3H, m) , 7.26-7.34 (2H, m) , 7.37- 7.45 (IH, m) , 10.39 (IH, s)
1- (2, 6-Difluorobenzoyl) -3- [2-fluoro-4- (1,1,2,2- tetarfluoroethoxy) phenyl] -3- (methoxymethyl) urea
(hereinafter, referred to as present compound (37))
Present compound (37)
Figure imgf000232_0001
1H-NMR (DMSO-d6 )6[ppm] : 3.27 (3H, s) , 4.98 (2H, s) , 6.71- 6.97 (IH, m) , 7.12-7.16 (2H, m) , 7.22-7.24 (IH, m) , 7.37- 7.40 (IH, m) , 7.50-7.54 (2H, m) , 10.90 (IH, brs)
1- (2, 6-Difluorobenzoyl) -3- (2-fluoro-4- trifluoromethylphenyl) -3- (methoxymethyl) urea (hereinafter, referred to as present compound (38))
Present compound (38)
Figure imgf000232_0002
1H-NMR (DMSO-d6 )δ[ppm] : 3.26 (3H, s) , 5.03 (2H, s) , 7.11-
7.15 (2H, m) , 7.47-7.46 (IH, m) , 7.51-7.52 (2H, m) , 7.81-
7.84 (IH, m) , 10.96 (IH, brs)
1- (2-Chloro-6-fluorobenzoyl) -3- [2-fluoro-4- (1,1,2,2- tetrafluoroethylthio) phenyl] -3- (methoxymethyl) urea
(hereinafter, referred to as present compound (39))
Present compound (39)
Figure imgf000233_0001
1H-NMR (DMSO-d6, measuring temperature : 80°C) δ [ppm] : 3.34 (3H, s), 5.03 (2H, s), 6.63 (IH, tt, J = 52.5, 3.8 Hz), 7.22 (IH, t, J = 8.7 Hz), 7.31 (IH, d, J = 8.0 Hz), 7.41- 7.48 (IH, m) , 7.54-7.64 (3H, m) , 10.67 (IH,' br s)
l-(2, 6-Difluorobenzoyl) -3- [2-fluoro-4- (1,1,2,2,3,3,3- heptafluoropropylthio) phenyl] -3- (methoxymethyl) urea
(hereinafter, referred to as present compound (40))
Present compound (40)
Figure imgf000233_0002
1H-NMR (DMSO-d6, measuring temperature : 80°C) δ [ppm] : 3.32 (3H, s), 5.03 (2H, s) , 7.03-7.12 (2H, m) , 7.45-7.54 (IH, m) , 7.56-7.62 (2H, m) , 7.65-7.71 (IH, m) , 10.66 (IH, br s)
1- (2-Chloro-6-fluorobenzoyl) -3- [2-fluoro-4- (1,1,2,2,3,3, 3-heptafluoropropylthio) phenyl] -3- (methoxymethyl) urea (hereinafter, referred to as present compound (41) )
Present compound (41)
Figure imgf000234_0001
1H-NMR (DMSO-de, measuring temperature : 8O0C) δ [ppm] : 3.31 (3H, s), 5.01-(2H, s), 7.16-7.22 (IH, m) , 7.27-7.31 (IH, m) , 7.40-7.47 (IH, m) , 7.57-7.60 (2H, m) , 7.65-7.70 (IH, m) , 10.68 (IH, br s)
Example 42
To a solution of 1.0 g of 1- (2, 6-difluorobenzoyl) -3- [2-fluoro-4- (trifluoromethylthio) phenyl] -3-
(methoxymethyl) urea in 10 ml of chloroform was added 0.61 g of meta-chloroperbenzoic acid (content; 65% by weight) under ice-cooling, and the mixture was stirred for 1 hour, and the mixture was allowed to stand at room temperature for 24 hours. To the reaction mixture was added 10 ml of chloroform, followed by washing with 20 ml of an aqueous saturated sodium bicarbonate solution three times. The organic layer was dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The resulting residue was purified by medium pressure preparative high performance liquid chromatography (ethyl acetate : hexane = 33:67) to obtain 0.49 g of 1- (2 , 6-difluorobenzoyl) -3- [2- fluoro-4- (trifluoromethylsulfinyl) phenyl] -3- (methoxymethyl) urea (hereinafter, referred to as present compound (42) ) .
Present compound (42]
Figure imgf000235_0001
1H-NMR (CDCl3 )δ[ppm] : 3.47(3H, s), 5.0β(2H, br) , 6.92- 6.96(2H, m) , 7.38-7.42 (IH, m) , 7.60-7.62 (2H, m) , 7.68- 7.7O(1H, m) , 8.20-8.40 (IH, br)
Examples 43 to 45
According to the same manner as that of Example 42, the following compounds were produced.
l-(2, 6-Difluorobenzoyl)-3-[2-fluoro-4-(l, 1,2,2- tetrafluoroethylsulfinyl) phenyl] -3- (methoxymethyl) urea (hereinafter, referred to as present compound (43))
Present compound (43)
Figure imgf000235_0002
1H-NMR (DMSO-d6, measuring temperature : 800C) δ [ppm] : 3.35 (3H, s), 5.07 (2H, s), 6.80 (IH, tdd, J = 51.2, 6.3, 4.1 Hz), 7.04-7.12 (2H, m) , 7.44-7.54 (IH, m) , 7.70-7.80 (3H, m) , 10.69 (IH, br s)
1, 3-Bis (methoxymethyl) -1- (2, 6-difluorobenzoyl) -3- [2- fluoro-4- (trifluoromethylsulfinyl) phenyl] urea (hereinafter, referred to as present compound (44))
Present compound (44)
Figure imgf000236_0001
1H-NMR (CDCl3 )δ[ppm] : 3.37(3H, s), 3.57(3H, s) , 4.82(2H, br) , 5.17(br, 2H), 6.83(2H, m) , 7.31-7.34 (IH, m),7.53(lH, m) , 7.67 (2H, m)
1, 3-Bis (methoxymethyl) -1- (2, 6-difluorobenzoyl) -3- [2- fluoro-4-(l,l,2, 2-tetrafluoroethylsulfinyl) phenyl] urea
(hereinafter, referred to as present compound (45) )
Present compound (45)
Figure imgf000236_0002
1H-NMR (DMSO-d6, measuring temperature : 8O0C) δ [ppm] : 3.24 (3H, s), 3.36 (3H, s), 4.81 (2H, s), 5.10 (2H, s), 6.85 (IH, tdd, J = 51.2, 6.4, 4.0 Hz), 7.04-7.13 (2H, m) , 7.49-7.59 (IH, m) , 7.66-7.73 (2H, m) , 7.77 (IH, d, J = 9.4 Hz)
Example 46
A solution of 1.0 g of 1- (2, 6-difluorobenzoyl) -3- [2- fluoro-4- ( trifluoromethylthio) phenyl] -3- (methoxymethyl) urea in 15 ml of chloroform was ice-cooled, 1.51 g of meta- chloroperbenzoic acid (content; 65% by weight) was added to the solution, and the mixture was stirred for 1 hour and allowed to stand at room temperature for 48 hours. To the reaction mixture was added 15 ml of chloroform, and the resulting mixture was washed with 30 ml of an aqueous saturated sodium bicarbonate solution three times. The organic layer was dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The resulting residue was purified by medium pressure preparative high performance liquid chromatography (ethyl acetate : hexane = 33:67^) to obtain 0.61 g of 1- (2, 6-difluorobenzoyl) -3- [2- fluoro-4- (trifluoromethylsulfonyl) phenyl] -3- (methoxymethyl) urea (hereinafter, referred to as present compound (46) ) .
Present compound (46)
Figure imgf000237_0001
1H-NMR (CDCl3 )δ[ppm] : 3.47(3H, s) , 5.08(2H, br) , 6.92- 6.96(2H, m) , 7.38-7.42 ( IH, m) , 7.64-7.68 ( IH, m) , 7.83- 7.89(2H, m) , 8.65(1H, br)
Examples 47 to 49
According to the same manner as that of Example 46, the following compounds were produced.
1- (2, β-Difluorobenzoyl) -3- [2-fluoro-4- ( 1, 1,2,2- tetrafluoroethylsulfonyl) phenyl] -3- (methoxymethyl) urea (hereinafter, referred to as present compound (47))
Present compound (47)
Figure imgf000238_0001
1H-NMR (DMSO-d6, measuring temperature : 80°C) δ [ppm] : 3.33 (3H, s), 5.09 (2H, s), 7.03 (IH, tt, J = 50.5, 5.3 Hz), 7.05-7.13 (2H, m) , 7.45-7.54 (IH, m) , 7.84-7.89 (IH, m) , 7.92-7.99 (2H, m) , 10.85 (IH, br s)
1, 3-Bis (methoxymethyl) -1- (2, 6-difluorobenzoyl) -3- [2- fluoro-4- ( trifluoromethylsulfonyl) phenyl] urea (hereinafter, referred to as present compound (48))
Present compound (48)
Figure imgf000238_0002
1H-NMR (CDCl3 )δ [ppm] : 3.38 (3H, s) , 3.57 (3H, s) , 4.82 (2H, br) , 5.20(2H, br) , 6.84 (2H, m) , 7.31-7.37 ( IH, m) , 7.75- 7.77 (1H, m) , 7.82-7.84 (2H, m)
1, 3-Bis (methoxymethyl) -1- (2, 6-dif luorobenzoyl) -3- [2- fluoro-4- (1,1,2, 2-tetrafluoroethylsulfonyl) phenyl] urea (hereinafter, referred to as present compound (49))
Present compound (49)
Figure imgf000239_0001
1H-NMR (DMSO-d6, measuring temperature : 8O0C) δ [ppm] : 3.24 (3H, s), 3.38 (3H, s), 4.82 (2H, s) , 5.14 (2H, s), 6.90- 7.22 (3H, m) , 7.50-7.59 (IH, m) , 7.79-7.86 (IH, m) , 7.91- 7.96 (IH, m) , 7.97-8.02 (IH, m)
Production Example 4
A mixture of 3.00 g of 2, 6-difluorobenzamide, 3.6 ml of a 36% aqueous formalin solution and 0.10 g of potassium carbonate was stirred at room temperature for 13 hours. The reaction mixture was added to 10 ml of water, the resulting mixture was stirred for 30 minutes, and filtered, and the resulting solid was washed with 40 ml of water.
The resulting solid was dried over diphosphorus pentaoxide under reduced pressure to obtain 2.05 g of 2, 5-difluoro-N- hydroxymethylbenzamide .
Figure imgf000239_0002
1H-NMR (DMSO-d6 )δ[ppm] : 4.63-4.66 (2H, m) , 5.87-5.91 (IH, m) , 7.13-7.17 (2H, m) , 7.48-7.52 (IH, m) , 9.25 (IH, brm) Production Example 5
To a solution of 10.0 g of 2, 6-difluoro-N- hydroxymethylbenzamide in 100 ml of methanol was added 10 ml of 35% hydrochloric acid, and the mixture was stirred at room temperature for 6 hours. The reaction mixture was concentrated under reduced pressure, and the resulting residue was dissolved in 200 ml of chloroform, and washed with 100 ml of water. The organic layer was dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain 10.71 g of 2 , 6-difluoro-N- methoxymethylbenzamide .
Figure imgf000240_0001
1H-NMR (CDCl3 )δ[ppm] : 3.44 (3H, s) , 4.90 (2H, d, J=8.0 Hz) , 6.51 (IH, br) , 6.94-7.00 (2H, m) , 7.36-7.44 (IH, m)
Example 1-(1)
To a solution of 1.00 g of 2, 6-difluoro-N- methoxymethylbenzamide and 0.64 ml of chlorotrimethylsilane in 10 ml of chloroform were dissolved was added dropwise a solution of 0.70 ml of triethylamine in 5.0 ml of
chloroform thereto at room temperature, and the mixture was stirred at 40°C for 40 minutes. Then, a solution of 1.50 g of bis (trichloromethyl) carbonate in 10 ml of chloroform was added dropwise thereto, and the mixture was stirred at room temperature for 30 minutes. The reaction mixture was concentrated under reduced pressure, and the resulting residue was dissolved in 10 ml of chloroform. The solution was added dropwise a solution of 0.63 g of 2-fluoro-N- methoxyτnethyl-4- (trifluoromethylthio) aniline and 1.4 ml of triethylamine in 10 ml of chloroform under ice-cooling, and the mixture was stirred at 50°C for 1 hour, and allowed to stand at room temperature for 6 days. The reaction mixture was washed with 20 ml of water. The organic layer was dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (ethyl acetate : hexane = 1:5), and was further purified by medium pressure
preparative high performance liquid chromatography (ethyl acetate: chloroform: hexane =-15:15:70) to obtain 0.18 g of present compound (1).
Example l-(2)
To a solution of 1.00 g of 3- (2, 6-difluorobenzoyl) -1- [2-fluoro-4- (trifluoromethylthio) phenyl] -1-
(methoxymethyl) urea in 10 ml of l-methyl-2-pyrrolidone was added 0.10 g of sodium hydroxide (content; 96% by weight) was added at 3°C under ice-cooling. The resulting mixture was stirred at the same temperature for 30 minutes, the mixture was added dropwise to a solution of 0.20 g of chloromethyl methyl ether in 1 ml of l-methyl-2-pyrrolidone at 2°C, and the mixture was stirred for 3 hours under ice- cooling. To the reaction mixture was added a mixture of 10 ml of an aqueous saturated ammonium chloride solution and 5 ml of water was added at 2 to 25°C, followed by extraction with 10 ml of ^ethyl acetate three times. The organic layer was washed with 10 ml of an aqueous saturated sodium chloride solution three times, dried over anhydrous
magnesium sulfate, and concentrated under reduced pressure. The resulting residue was purified by medium pressure preparative high performance liquid chromatography (ethyl aceta'te : hexane = 17:83) to obtain 0.21 g of present
compound ( 1 ) .
Example 50
To a solution of 1.01 g of 1- (2, 6-difluorobenzoyl) -3- (4-trifluoromethylthiophenyl) urea in 10.0 ml of l-methyl-2- pyrrolidone was added 0.67 ml of chloromethyl methyl ether under ice-cooling, and 266 mg of sodium hydride (content; 55% by weight in oil) was subsequently added at 3°C to 5°C. The resulting mixture was stirred for 4 hours under ice- cooling. To the reaction mixture was added a mixture of 10 ml of an aqueous saturated ammonium chloride solution and 5 ml of water under ice-cooling, followed by extraction with 10 ml of ethyl acetate three times. The organic layers were combined, washed with an aqueous saturated sodium chloride solution three times, dried over anhydrous
magnesium sulfate, and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (ethyl acetate : chloroform: hexane = 1:1:4), and was further purified by medium pressure preparative high performance liquid chromatography (ethyl
acetate : hexane = 30:70) to obtain 0.13 g of 1,3- bis (methoxymethyl) -1- (2, 6-difluorobenzoyl) -3- (4- trifluoromethylthio) phenylurea (hereinafter, referred to as present compound (50)).
Present compound (50)
Figure imgf000243_0001
1H-NMR(CDCl3)O(PPm): 3.35 (3H, brs) , 3.48 (3H, brs) ,
4.88 (2H,brs) , 5.11 (2H, brs) , 6.85-6.89 (2H,m) , 7.32- 7.40(3H,m) 7.64-7.66 (2H, m)
Example 51
To a solution of 1.01 g of 1- (2, 6-difluorobenzoyl) -3- [2-chloro-4- (tπfluoromethylthio) phenyl] urea in 10.0 ml of l-methyl-2-pyrrolidone was added 0.61 ml of chloromethyl methyl ether under ice-cooling and, then, 243 mg of sodium hydride (content; 55% by weight in oil) was added at 3°C to 5°C. The resulting mixture was stirred for 4 hours under ice-cooling. To the reaction mixture was added a mixture of 10 ml of an aqueous saturated ammonium chloride solution and 5 ml of water under ice-cooling, followed by extraction with 10 ml of ethyl acetate three times. The organic layers were combined, washed with an aqueous saturated sodium chloride solution three times, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (ethyl acetate : chloroform: hexane = 1:1:4), and was further purified by medium pressure preparative high performance liquid chromatography (ethyl
acetate : hexane = 15:85) to obtain 0.53 g of 1,3- bis (methoxymethyl) -1- (2, 6-difluorobenzoyl) -3- (2-chloro-4- trifluoromethylthio) phenylurea (hereinafter, referred to as present compound (51) ).
Present compound (51)
Figure imgf000244_0001
1 H-NMR (DMSO-d6, measuring temperature : 800C) δ (ppm) :
3.05 (3H,brs) , 3.23 ( 3H, brs) , 4.79 (2H, brs) , 5.06 (2H, brs) , 7.04-7.09(2H,m) , 7.50-7.52 (2H,m) 7.69-7.71 ( IH, m) ,
7.90(lH,m)
Example 52
To a solution of 1.01 g of 3- [4- (3-chloro-5- trifluoromethyl-2-pyridylthio) -2-fluorophenyl] -1- (2, 6- difluorobenzoyl) urea in 10.0 ml of l-methyl-2-pyrrolidone was added 0.5 ml of chloromethyl methyl 'ether under ice- cooling and, then, 198 mg of sodium hydride (content; 55% by weight in oil) was added at 2°C to 8°C. The resulting mixture was stirred for 4 hours under ice-cooling. To the reaction mixture was added a mixture of 10 ml of an aqueous saturated ammonium chloride solution and 5 ml of water under ice-cooling, followed by extraction with 10 ml of ethyl acetate three times. The organic layers were
combined, washed with an aqueous saturated sodium chloride solution three times, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The resulting residue was purified by silica gel column
chromatography (ethyl acetate : chloroform: hexane = 1:1:4) to obtain 0.78 g of 1, 3-bis (methoxymethyl) -3- [4- (3-chloro-5- trifluoromethyl-2-pyridylthio) -2-fluorophenyl] -1- (2, 6- difluorobenzoyl) urea (hereinafter, referred to as present compound (52) ).
Present compound (52)
Figure imgf000245_0001
1H-NMR(CDCl3)O(PPm) : 3.39 (3H, brs) , 3.55 ( 3H, brs) ,
4.86 (2H,brs) , 5.15 (2H, brs) , 6.86 (2H,m) , 7.33-7.45 (4H,m)
7.79-7.80 (IH, m) , 8.31(lH,m) Example 53
To a solution of 1.01 g of 3- [3, 5-dichloro-4- (3- chloro-5-trifluoromethyl-2-pyridyloxy) phenyl] -1- (2, 6- difluorobenzoyl) urea in 10.0 ml of l-methyl-2-pyrrolidone was added 0.46 ml of chloromethyl methyl ether under ice- cooling and, then, 185 mg of sodium hydride (content; 55% by weight in oil) was added at 2°C to 8°C. The resulting mixture was stirred for 3 hours under ice-cooling. To the reaction mixture was added a mixture of 10 ml of an aqueous saturated ammonium chloride solution and 5 ml of water under ice-cooling, followed by extraction with 10 ml of ethyli acetate three times. The organic layers were
combined, washed with an aqueous saturated sodium chloride solution three times, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The resulting residue was purified by silica gel column
chromatography (ethyl acetate : chloroform: hexane = 1:1:4), and was further purified by medium pressure preparative high performance liquid chromatography (ethyl
acetate: hexane = 15:85) to obtain 0.17 g of 1,3- bis (methoxymethyl) -3- [3, 5-dichloro-4- (3-chloro-5- trifluoromethyl-2-pyridyloxy) phenyl] -1- (2,6- difluorobenzoyl) urea (hereinafter, referred to as present compound (53) ).
Present compound (53)
Figure imgf000247_0001
1 H-NMR ( CDCl3 ) S (PPm) : 3 . 37 ( 3H, brs ) , 3 . 50 ( 3H, brs ) ,
5.00(2H,brs) , 5.11 (2H, brs) , 6.93-6.97 (2H,m) , 7.37- 7.44(3H,m) 8.0*4(lH,s), 8.19(lH,s)
Example 54
To a solution of 1.01 g of 1- (2, 6-difluorobenzoyl) -3- [2-methyl-4- ( trifluoromethylthio) phenyl] urea in 10.0 ml of l-methyl-2-pyrrolidone was added 0.64 ml of chloromethyl methyl ether under ice-cooling and, then, 256 mg of sodium hydriNde (content; 55% by weight in oil) was added at 2°C to 11°C. The resulting mixture was stirred for 4 hours under ice-cooling. To the reaction mixture was added a mixture of 10 ml of an aqueous saturated ammonium chloride solution and 5 ml of water, followed by extraction with 10 ml of ethyl acetate three times. The organic layers were
combined, washed with an aqueous saturated sodium chloride solution three times, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The resulting residue was purified by silica gel column
chromatography (ethyl acetate : chloroform: hexane = 1:1:4), and was further purified by medium pressure preparative high performance liquid chromatography (ethyl
acetate: hexane = 18:85) to obtain 0.07 g of 1,3- bis (methoxymethyl) -1- (2, 6-difluorobenzoyl) -3- [2-methyl-4- (trifluoromethylthio) phenyl] urea (hereinafter, referred to as present compound 54) ).
Present compound (54)
Figure imgf000248_0001
1H-NMR(CDCl3)O(PPm): 2.28 (3H, brs) , 3.33 ( 3H, brs) ,
3.47 (3H,brs) , 4.76 (2H, brs) , 5.37 (2H, brs) , 6.87(2H,m),
7.32(2H7ITi), 7.48(lH,s), 7.56(lH,m)
Example 55
"To a solution of 1.01 g of 1- (2, 6-difluorobenzoyl) -3- [2, 3-dimethyl-4- (trifluoromethylthio) phenyl] urea in 10.0 ml of l-methyl-2-pyrrolidone was added 0.62 ml of chloromethyl methyl ether under ice-cooling and, then, 247 mg of sodium hydride (content; 55% by 'weight in oil) was added at 1°C to 4°C. The resulting mixture was stirred for 4 hours under ice-cooling. To the reaction mixture was added a mixture of 10 ml of an aqueous saturated ammonium chloride solution and 5 ml of water under ice-cooling, followed by extraction with 10 ml of ethyl acetate three times. The organic layers were combined, washed with an aqueous saturated sodium chloride solution three times, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (ethyl acetate : chloroform: hexane = 1:1:4), and was further purified by medium pressure preparative high performance liquid chromatography (ethyl
acetate: hexane = 15:85) to obtain 0.66 g of 1,3- bis (methoxymethyl) -1- (2, 6-difluorobenzoyl) -3- [2, 5-dimethyl-
4- (trifluoromethylthio) phenyl] urea (hereinafter, referred to as present compound (55)).
Present compound (55)
Figure imgf000249_0001
1H-NMR(CDCl3)O(PPm): 2.21 (3H, brs) , 2.53 (3H, brs) ,
3.32 (3H,brs) , 3.46 (3H, brs) , 4.74 (2H, brs) , 5.38 (2H, brs) , 6.86(2H,m), 7.17(lH,m), 7.33(lH,m), 7.56(lH,m)
Example 56
■ To a solution of 1.01 g of 1- (2, 6-difluorobenzoyl) -3- [2-fluoro-4- (t-butoxycarbonyl) phenyl] urea in 10.0 ml of 1- methyl-2-pyrrolidone was added 0.64 ml of chloromethyl methyl ether under ice-cooling and, then, 254 mg of sodium hydride (content; 55% by weight in oil) was added at 2°C to 11°C. The resulting mixture was stirred for 3 hours under ice-cooling. To the reaction mixture was added a mixture of 10 ml of an aqueous saturated ammonium chloride solution and 5 ml of water under ice-cooling, followed by extraction with 10 ml of ethyl acetate three times. The organic layers were combined, washed with an aqueous saturated sodium chloride solution three times, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure, The resulting residue was purified by silica gel column chromatography (ethyl acetate : chloroform: hexane = 1:1:4), and was further purified by medium pressure preparative high performance liquid chromatography (ethyl
acetate : hexane = 15:85) to obtain 0.70 g of a white solid. This was recrystallized to obtain 0.46 g of 1,3- bis (methoxymethyl) -1- (2, β-difluorobenzoyl) -3- [2-fluoro-4- (t-butoxycarbonyl) phenyl] urea (hereinafter, referred to as present compound 56) ) .
Present compound 56
Figure imgf000250_0001
1H-NMR(CDCl3)O(PPm): 1.59(9H,s), 3.39(3H,s), 3.49(3H,s), 4.86(2H,brs) , 5.12 (2H, brs) , 6.83-6.88 (2H,m) , 7.31- 7.39(2H,m), 7.73-7.78 (2H,m)
Example 57
To a solution of 1.01 g of 1- (3-chloropyridin-2- ylcarbonyl) -3- [2-fluoro-4- (trifluoromethylthio) phenyl] urea in 10.0 ml of l-methyl-2-pyrrolidone was added 0.64 ml of chloromethyl methyl ether under ice-cooling and, then, 254 mg of sodium hydride (content; 55% by weight in oil) was added at 2°C to 5°C. The resulting mixture was stirred for 3 hours under ice-cooling. To the reaction mixture was added a mixture of 10 ml of an aqueous saturated ammonium chloride solution and 5 ml of water under ice-cooling, followed by extraction with 10 ml of ethyl acetate three times. The organic layers were combined, washed with an aqueous saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (acetonitrile : chloroform= 1:20), and was further purified by medium pressure preparative high performance liquid chromatography (ethyl acetate : hexane = 20:80) to obtain 0.73 g of 1, 3-bis (methoxymethyl) -1- (3- chloropyridin-2-ylcarbonyl) -3- [2-fluoro-4- ( trifluoromethylthio) phenyl] urea (hereinafter, referred to as present compound (57)).
Present compound (57)
Figure imgf000251_0001
1H-NMR(CDCl3 )δ(ppm) : 3.39(6H,s), 4.93 (2H, brs) , 5.08 (2H, brs) , 7.30-7.33(1H7ITi) , 7.44-7.49 (2H,m) , 7.76-7.79 (2H,m) , 8.39- 8.40 (IH, m)
Example 58
To a solution of 1.01 g of 1- (3, 5-dichloropyridin-4- ylcarbonyl) -3- [2-fluoro-4- (trifluoromethylthio) phenyl] urea in 10.0 ml of l-methyl-2-pyrrolidone was1 added 0.59 ml of chloromethyl methyl ether under ice-cooling and, then, 234 mg of sodium hydride (content; 55% by weight in oil) was added at 20C to 6°C. The resulting mixture was stirred for 3 hours under ice-cooling. To the reaction mixture was added a mixture of 10 ml of an aqueous saturated ammonium chloride solution and 5 ml of water, followed by extraction with 10 ml of ethyl acetate three times. The organic layers were combined, washed with an aqueous saturated sodium chloride solution three times, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (ethyl acetate : chloroform: hexane = 1:1:4), and was further purified by medium pressure preparative high performance liquid chromatography (ethyl
acetate : hexane = 15:85) to obtain 0.12 g of 1,3- bis (methoxymethyl) -1- (3, 5-dichloropyridin-4-ylcarbonyl) -3- [2-fluoro-4- (trifluoromethylthio) phenyl] urea (hereinafter, referred to as present compound (58)).
Present compound (58)
Figure imgf000252_0001
1 H-NMR (DMSO-de, measuring temperature : 800C) δ (ppm) : 3.24 (3H,brs) , 3.38 (3H, brs) , 4.67 (2H, brs) , 5.11 (2H, brs) , 7.62 (2H,m) , 7.72(lH,m), 8.64(2H,s)
Example 59
To a solution of 1.01 g of 1- (2, 6-difluorobenzoyl) -3- (4-difluoromethylthio-2-fluorophenyl) urea in 10.0 ml of 1- methyl-2-pyrrolidone was added 0.67 ml of chloromethyl methyl ether under ice-cooling and, then, 266 mg of sodium hydride (content; 55% by weight in oil) was added at 2°C to 8°C. The resulting mixture was stirred for 3 hours under ice-cooling. To the reaction mixture was added a mixture of 10 ml of an aqueous saturated ammonium chloride solution and 5i ml of water under ice-cooling, followed by extraction with 10 ml of ethyl acetate three times. The organic layers were combined, washed with an aqueous saturated sodium chloride solution three times, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (ethyl acetate: chloroform: hexane = 1:1:4), and was further purified by medium pressure preparative high performance liquid chromatography (ethyl
acetate: hexane = 15:85) to obtain 0.39 g of 1,3- bis (methoxymethyl) -1- (2, 6-difluorobenzoyl) -3- (4- difluoromethylthio-2-fluorophenyl) urea (hereinafter, referred to as present compound (59) ) .
Present compound (59)
Figure imgf000254_0001
1H-NMR(CDCl3 )δ(ppm) : 3.38 ( 3H, brs ) , 3.53 (3H, brs) ,
4.82 (2H,brs) , 5.11 (2H, brs) , 6.69-6.97 (IH, m) , 6.85(2H,m), 7.30-7.41(4H,m)
Example 60
To a solution of 1.01 g of 1- (2-chloro-6- fluorobenzoyl) -3- (4-difluoromethylthio-2-fluorophenyl) urea in 10.0 ml of l-methyl-2-pyrrolidone was added 0.64 ml of chloromethyl methyl ether under ice-cooling and, then, 255 mg of-, sodium hydride (content; 55% by weight in oil) was added at 1°C to 5°C. The resulting mixture was stirred for 3 hours under ice-cooling. To the reaction mixture was added a mixture of 10 ml of an aqueous saturated ammonium chloride solution and 5 ml of water under ice-cooling, followed by extraction with 10 ml of ethyl acetate three times. The organic layers were combined, washed with an aqueous saturated sodium chloride solution three times, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (ethyl
acetate : chloroform: hexane = 1:1:4), and was further
purified by medium pressure preparative high performance liquid chromatography (ethyl acetate : hexane = 15:85) to obtain 0.38 g of 1, 3-bis (methoxymethyl) -1- (2-chloro-6- fluorobenzoyl) -3- (4-difluoromethylthio-2-fluorophenyl) urea (hereinafter, referred to as present compound (60)).
Present compound (60)
Figure imgf000255_0001
1 H-NMR (DMSO-d5, measuring temperature : 80°C) δ (ppm) :
3.03(3H,brs) , 3.22 (3H, brs) , 4.74 (2H, brs) , 5.06 (2H, brs) , 7.22(lH,m), 7.33(lH,m), 7.44-7.55 (4H,m) , 7.37-7.65 (IH, m) Example 61
To a solution of 0.38 g of 1- (2 , 6-difluorobenzoyl) -3- [2-fluoro-4- (1,1,2,3,3, 3-hexafluoropropylthio) phenyl] urea in 4.0 ml of l-methyl-2-pyrrolidone were added 0.20 ml of chloromethyl methyl ether and 80 mg of sodium hydride
(content; 55% by weight in oil) at 2°C under ice-cooling. The resulting mixture was stirred for 4 hours under ice- cooling. To the reaction mixture was added a mixture of 4 ml of an aqueous saturated ammonium chloride solution and 2 ml of water under ice-cooling, followed by extraction with 4 ml of ethyl acetate three times. The organic layers were combined, washed with an aqueous saturated sodium chloride solution three times, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (ethyl acetate : chloroform: hexane = 1:1:4) to obtain 0.28 g of 1, 3-bis (methoxymethyl) -1- (2, 6- difluorobenzoyl) -3- [2-fluoro-4- (1,1,2,3,3,3- hexafluoropropylthio) phenyl] urea (hereinafter, referred to as present compound (61)).
Present compound (61)
Figure imgf000256_0001
1H-NMR(CDCl3)O(PPm): 3.37(3H,s), 3.55 (3H, brs) , 4.7- 4.9(3H,m), 5.14 (2H, brs) , 6.83 (2H,m) , 7.32-7.36 ( IH, m) , 7.42- 7.49(S3H,m)
Example 62
To a solution of 777 mg of 1- (2-chloro-6- fluorobenzoyl) -3- [2-fluoro-4- (1,1,2,2,3,3,3- heptafluoropropylthio) phenyl] urea in 7 ml of 1,3- dimethylimidazolinone was added 367 mg of chloromethyl methyl ether under ice-cooling and, then, 166 mg of sodium hydride (content; 55% by weight in oil) was added thereto. The resulting mixture was stirred at 5°C for 2 hours. To the reaction mixture were added 10 ml of an aqueous
saturated ammonium chloride solution and 10 ml of ethyl acetate, the mixture was stirred for 30 minutes, followed by addition of 50 ml of ethyl acetate, and the mixiture was separeated into layers. The organic layer was washed sequentially with water and an aqueous saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The resulting residue was purified by medium pressure preparative high performance liquid chromatography (ethyl acetate : hexane = 20:80) to obtain 300 mg of 1, 3-bis (methoxymethyl) -1- (2- chloro-6-fluorobenzoyl)-3- [2-fluoro-4- (1,1,2,2,3,3,3- heptafluoropropylthio) phenyl] urea (hereinafter, referred to as present compound (62) ).
Present compound (62)
Figure imgf000257_0001
1H-NMR (DMSO-d6, measuring temperature : 80°C) δ (ppm) : 3.21 (3H,-s), 3.36 (3H, s), 4.'76' (2H, s), 5.09 (2H,' s), 7.19 (IH, t, J = 8.8 Hz), 7.32 (IH, d, J = 8.2 Hz), 7.45-7.52 (IH, m) , 7.55-7.-63 (2H, m) , 7.68-7.74 (IH, m)
Example 63
To a solution of 600 mg of 1- (2, 6-difluorobenzoyl) -3- [2-fluoro-4- (2, 2, 2-trifluoroethylthio) phenyl] urea in 15 ml of 1, 3-dimethyl-2-imidazolidinone was added 355 mg of chloromethyl methyl ether under ice-cooling, and, then, 147 mg of sodium hydride (content; 55% by weight in oil) was added thereto. The resulting mixture was stirred at 40C for 2 hours. To the reaction mixture were added 10 ml of an aqueous saturated ammonium chloride solution and 10 ml of ethyl acetate, and the mixture was stirred for 30 minutes. To the resulting mixture was added 50 ml of ethyl acetate, and the mixture was separated into layers. The organic layer was washed sequentially with water and an aqueous saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The resulting residue was purified by medium pressure preparative high performance liquid chromatography (ethyl acetate : hexane = 25:75) to obtain 551 ml of 1,3- bis (methoxymethyl) -1- (2, 6-difluorobenzoyl) -3- [2-fluoro-4- (2,2, 2-trifluoroethylthio) phenyl] urea (hereinafter,
referred to as present compound (63)).
Present compound 63
Figure imgf000258_0001
1H-NMR (DMSO-d, measuring temperature: 80°C)δ(ppm) : 3.24 (3H, s) , 3.33 (3H, s) , 4.01 (2H, q, J = 10.2 Hz) , 4.79 (2H, s) , 5.01 (2H, s) , 7.04-7.14 (2H, m) , 7.25-7.38 (2H, m) , 7.43-7.60 (2H, m)
Example 64
To a solution of 800 mg of 3- [2-chloro-4- (difluoromethylthio) phenyl] -1- (2, β-difluorobenzoyl) urea in 15 ml of 1, 3-dimethyl-2-imidazolidinone was added 1.1 g of chloromethyl methyl ether and, then, 300 mg of sodium hydride (.content; 60% by weight in oil) was added. The resulting mixture was stirred at room temperature for 1 hour. To the reaction mixture was added 80 ml of ethyl acetate, and the resulting mixture was washed sequentially with water and an aqueous saturated sodium• chloride
solution, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The resulting residue was purified by medium pressure preparative high
performance liquid chromatography (ethyl acetate : hexane = 15:85) to obtain 520 mg of 1, 3-bis (methoxymethyl) -3- [2- chloro-4- (difluoromethylthio) phenyl] -1- (2, 6- difluorobenzoyl) urea (hereinafter, referred to as present compound ( 64 ) ) .
Present compound (64)
Figure imgf000259_0001
1H-NMR (DMSO-d6, measuring temperature: 80°C)δ(ppm): 3.24 (3H, s), 3.37 (3H, s), 4.81 (2H, s), 5.04 (2H, s) , 7.08 (2H, t, J = 8.5 Hz), 7.43 (IH, d, J = 8.5 Hz), 7.47-7.58 (2H, m) , 7.50 (IH, t, J = 56.0 Hz), 7.76 (IH, d, J = 1.9 Hz)
Example 65 A solution of 0.32 g of 2, β-difluorobenzoyl isocyanate in 0.4 ml of diethyl ether was added to a solution of 0.41 g of N-methoxyinethyl-4- (difluoromethylthio) -2-fluoroaniline in 1.6 ml of diethyl ether under ice-cooling, and the mixture was stirred at room temperature for 2 hours. The reaction mixture was concentrated under reduced pressure, and the resulting residue was purified by medium pressure preparative high performance liquid chromatography to obtain 0.40 g of 1- (2, 6-difluorobenzoyl) -3- [2-fluoro-4- (difluoromethylthio) phenyl] -3- (methoxymethyl) urea
(hereinafter, referred to as present compound 65) ) .
Present compound (65)
Figure imgf000260_0001
1 H-NMR (DMSO-d6, measuring temperature : 80°C) δ (ppm) :
3.31(3H,s), 4.99(2H,s), 7.06-7.15 (2H,m) , 7.37-7.65 ( IH, m) ,
7.42-7.53(4H,m) , 10.56 ( IH, brs)
Example 66
To a solution of 1.12 g of 2-fluoro-4- (2 , 2, 2- trifluoroethylthio) aniline in 10 ml of methanol were added 324 mg of paraformaldehyde and 4.80 g of sodium methoxide
(28% by weight methanol solution) , and the mixture was stirred at room temperature for 7 hours. To the reaction mixture was added 50 ml of water, and the mixture was extracted with tert-butyl methyl ether three times. The organic layer was washed with an aqueous1 saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain 1.39 g of 2-fluoro-N-methoxymethyl-4- (2,2,2- trifluoroethylthio) aniline . This aniline compound was dissolved in 10 ml of tert-butyl methyl ether, and to the solution was slowly added a solution of 910 mg of 2,6r difluorobenzoyl isocyanate in 3.0 ml of tert-butyl methyl ether, and the resulting mixture was stirred at room temperature for 30 minutes. This reaction mixture was concentrated under reduced pressure. The resulting residue was purified by medium pressure preparative high
performance liquid chromatography (ethyl acetate : hexane = 25:75) to obtain 1.10 g of 1- (2, 6-difluorobenzoyl) -3- [2- fluoro-4- (2, 2, 2-trifluoroethylthio) phenyl] -3- (methoxymethyl) urea (hereinafter, referred to as present compound (66) ) .
Present comparative 66
Figure imgf000261_0001
1H-NMR ( DMSO-d6 , measuring temperature : 80°C ) δ (ppm) : 3 . 30 ( 3H, s ) , 4 . 02 ( 2H, q, J = 10 . 2 Hz ) , 4 . 96 ( 2H, s ) , 7 . 07 ( 2H, t, J = 8.1 Hz), 7.30-7.40 (2H, m) , 7.42-7.54 (2H, m) , 10.45 (IH, br s)
Example 67
To a solution of 1.8 g of 2-fluoro-4- (1, 1, 2, 3, 3, 3- hexafluoropropylthio) aniline in 10 ml of methanol were added 400 mg of paraformaldehyde and 5.92 g of sodium methoxide (28% by weight methanol solution) , and the mixture was stirred at room temperature for 6 hours. To this reaction mixture was added 50 ml of water, followed by extraction with tert-butyl methyl ether three times. The organic layer was washed with an aqueous saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain 1.98 g of 2-fluoro-N-methoxymethyl-4- (1,1,2,3,3,3- hexafluoropropylthio) aniline . To a solution of 300 mg of 2-fluoro-N-methoxymethyl-4- (1,1,2,3,3,3- hexafluoropropylthio) aniline in 5 ml of tert-butyl methyl ether was slowly added a solution of 163 mg of 2,6- difluorobenzoyl isocyanate in 1.0 ml of tert-butyl methyl ether, and the mixture was stirred at room temperature for 30 minutes. This reaction mixture was concentrated under reduced pressure. The resulting residue was purified by medium pressure preparative high performance liquid
chromatography (ethyl acetate : hexane = 25:75) to obtain 290 mg of 1- (2, 6-difluorobenzoyl) -3- [2-fluoro-4- ( 1, 1, 2, 3, 3, 3- hexafluoropyopylthio) phenyl] -3- (methoxymethyl) urea
(hereinafter, referred to as present compound (67)).
Present compound (67)
Figure imgf000263_0001
1H-NMR (DMSO-d6, measuring temperature : 80°C) δ (ppm) : 3.32
(3H, s), 5.02 (2H, s), 6.01-6.24 (IH, m) , 7.07 (2H, t, J = 8.1 Hz), 7.43-7.63 (4H, m) , 10.60 (IH, br s)
Production Example 6
>v,To a solution of 580 mg of 2-fluoro-4- (trifluoromethylthio) acetoanilide in 5 ml of 1, 3-dimethyl- 2-imidazolidinone was added 382 mg of bromoethyl methyl ether, then, 120 mg of sodium hydride (content; 55% by weight in oil) was added/ and the mixture was stirred at room temperature for 1 hour. To the reaction mixture was added 50 ml of ethyl acetate, and washed sequentially with water and an aqueous saturated sodium chloride solution. The organic layer was dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain 632 mg of 2-fluoro-N- (2-methoxyethyl) -4- (trifluoromethylthio) acetoanilide.
2-Fluoro-N- (2-methoxyethyl) -4- (trifluoromethylthio) - acetoanilide
Figure imgf000264_0001
1H-NMR (CDCl3 )δ(ppm) : 1.88 (3H, s), 3.27 (3H, s), 3.39-3.52 (IH, m) , 3.56-3.76 (2H, m) , 3.95-4.09 (IH, m) , 7.38-7.44 (IH, m) , 7.46-7.53 (2H, m)
Production Example 7
To a solution of 632 mg of 2-fluoro-N- (2- methoxyethyl) -4- (trifluoromethylthio) acetoanilide in 15 ml of methanol was added 5 ml of 35% hydrochloric acid, and the mixture was heated under reflux for 6 hours. The reaction mixture was allowed to cool to room temperature, a 2N aqueous sodium hydroxide solution was added thereto to adjust to pH 10, followed by extraction with tert-butyl methyl ether three times. The organic layer was dried over anhydrous magnesium sulfate1, and concentrated under reduced pressure. The resulting residue was purified by medium pressure preparative high performance liquid chromatography (ethyl acetate : hexane = 10:90) to obtain 492 mg of 2- fluoro-N- (2-methoxyethyl) -4- (trifluoromethylthio) aniline.
2-Fluoro-N- (2-methoxyethyl) -4- (trifluoromethylthio) aniline
Figure imgf000264_0002
1H-NMR ( CDCl3 ) δ ( ppm) : 3 . 35 ( 2H , q , J = 5 . 3 Hz ) , 3 . 40 ( 3H , s), 3.63 (2H, t, J = 5.3 Hz), 4.56 (IH, br) , 6.67 (IH, t, J = 8.7 Hz) , 7.21-7.33 (2H, m)
Example 68
A solution of 330 mg of 2, 6-difluorobenzoyl isocyanate in 1.0 ml of ethyl acetate was added to a solution of 485 mg of 2-fluoro-N- (2-methoxyethyl) -4-
(trifluoromethylthio) aniline at room temperature, and the mixture was stirred at room temperature for 2 hours. The reaction mixture was washed sequentially with water and an aqueous saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The resulting residue was purified by medium pressure preparative high performance liquid chromatography (ethyl acetate : hexane = 34:66) to obtain 560 mg of l-(2,6- difluorobenzoyl) -3- [2-fluoro-4-
(trifluoromethylthio) phenyl'] -3- (3-methoxyethyl) urea
(hereinafter, referred to as present compound (68)).
Present compound (68)
Figure imgf000265_0001
1H-NMR (DMSO-d6, measuring temperature : 8O0C) δ (ppm) : 3.16
(3H, s) , 3.47 (2H, t, J = 5.6 Hz) , 3.80 (2H, t, J = 5.6 Hz) , 7.01-7.11 (2H, m) , 7.42-7.51 (IH, m) , 7.51-7.59 (2H, m) , 7.60-7.68 (IH, m) , 10.49 (IH, br s)
Production Example 8
To a solution of 5.0 g of 2-fluoro-4-
(trifluoromethylthio) acetoanilide in 30 ml of 1, 3-dimethyl- 2-imidazolidinone was added 5.0 g of 2- (2- bromoethoxy) tetrahydro-2H-pyran, then, 980 mg of sodium hydride (content; 55% by weight in oil) was added, and the resulting mixture was stirred at 70°C for 3 hours. To the reaction mixture was added 100 ml of water, followed by extraction with ethyl acetate two times. The organic layer was washed sequentially with water and an aqueous saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The resulting residue was purified by silica gel chromatography (ethyl acetate : hexane = 1:2) to obtain 6.09 g of 2-fluoro- N- [2- (2-tetrahydro-2H-pyranyloxy) ethyl] -4- (trifluoromethylthio) acetoanilide.
2-Fluoro-N- [2- (2-tetrahydro-2H-pyranyloxy) ethyl] -A- (trifluoromethylthio) acetoannlide
Figure imgf000266_0001
1H-NMR (CDCl3 )δ(ppm) : 1.27-1.76 (6H, m) , 1.89 (3H, s), 3.39-4.19 (6H, m) , 4.43-4.60 (IH, m) , 7.38-7.54 (3H, m) Production Example 9
To a solution of 820 mg of 2-fluoro-N- [2- (2- tetrahydro-2H-pyranyloxy) ethyl] -A-
(trifluoromethythio) acetoanilide in 10 ml of methanol was added 5 ml of 35% hydrochloric acid, and the resulting mixture was heated under reflux for 1 hour. The reaction mixture was allowed to cool to room temperature, 30 ml of a 2N aqueous sodium hydroxide solution was added to adjust to pH 10, followed by extraction with tert-butyl methyl ether three times. The organic layer was dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain 535 mg of N- (2-hydroxyethyl) -2-fluoro-4- (trifluoromethylthio) aniline.
N- (2-hydroxyethyl) -2-fluoro-4- (trifluoromethylthio) aniline
Figure imgf000267_0001
1H-NMR (CDCl3 )δ(ppm) : 1.64 (IH, t, J = 4.8 Hz), 3.38 (2H, q, J = 4.8 Hz), 3.89 (2H, q, J = 4.8 Hz), 4.47-4.67 (IH, br m) , 6.70 (IH, t, J = 8.7 Hz), 7.21-7.36 (2H, m)
Production Example 10
A solution of 373 mg of 2, 6-difluorobenzoyl isocyanate in 1.0 ml of ethyl acetate was added to a solution of 520 mg of N- (2-hydroxyethyl) -2-fluoro-4- (trifluoromethylthio) aniline at room temperature in 7 ml of ethyl acetate, and the resulting mixture was stirred for 1 hour. The reaction mixture was concentrated under reduced pressure. The resulting residue was purified by medium pressure preparative high performance liquid chromatography (ethyl acetate : hexane = 34:66) to obtain 460 mg of l-(2,6- difluorobenzoyl) -3- [2-fluoro-4-
(trifluoromethylthio) phenyl] -3- (2-hydroxyethyl ) uera .
1- (2, 6-Difluorobenzoyl) -3- [2-fluoro-4- (trifluoromethylthio) phenyl] -3- (2-hydroxyethyl) uera
Figure imgf000268_0001
1H-NMR (CDCl3 )δ(ppm) : 1.64 (IH, br s) , 3.66-4.06 (4H, m) , 6.92 (2H, t, J = 8.6 Hz) , 7.32-7.59 (5H, m)
Example 69
-To a solution of 284 mg of 1- (2, 6-difluorobenzoyl) -3- [2-fluoro-4- (trifluoromethylthio) phenyl] -3- (2- hydroxyethyl) urea in 5 ml of ethyl acetate was added 98 mg of triethylamine, then, 56 mg of acetyl chloride was added thereto, and the resulting mixture was stirred at room temperature for 2 hours. This reaction mixture was
filtered through Celite, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by medium pressure preparative high performance liquid chromatography (ethyl acetate: hexane = 25:75) to obtain 50 mg of l-acetyl-3- (2-acetoxyethyl) -1- (2, β-difluorobenzoyl) - 3- [2-fluoro-4- (trifluoromethylthio) phenyl] urea (hereinafter, referred to as present compound (69)).
Present compound (69)
Figure imgf000269_0001
1H-NMR (CDCl3 )δ(ppm) : 1.97 (3H, s) , 2.37 (3H, s), 3.96-4.53 (4H, m) , 6.69-6.87 (2H, m) , 7.25-7.36 (IH, m) , 7.37-7.49 (2H, m) , 7.51-7.59 (IH, m)
Example 70
To a solution of 300 mg of 1- (2, 6-difluorobenzoyl) -3- [2-fluoro-4- (trifluoromethylthio) phenyl] -1-methylurea in 4 ml of 1, 3-dimethyl-2-imidazolidinone was added 115 mg of benzyl chloromethyl ether at O0C and, then, 35 mg of sodium hydride (content; 55% by weight in oil) was added thereto. The resulting mixture was stirred at room temperature for 1 hour. To the reaction mixture was added 10 ml of an
aqueous saturated ammonium chloride solution, the mixture was stirred for 30 minutes, 50 ml of ethyl acetate was added thereto, and the mixture was separated into layers. The organic layer was washed sequentially with water and an aqueous saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The resulting residue was purified by medium pressure preparative high performance liquid chromatography (ethyl acetate : hexane = 15:85) to obtain 206 mg of 3- benzyloxymethyl-1- (2, 6-difluorobenzoyl) -3- [2-fluoro-4- (trifluoromethylthio) phenyl] -1-methylurea (hereinafter, referred to as present compound (70) ) .
Present compound (70)
Figure imgf000270_0001
1H-NMR (CDCl3 )δ(ppm) : 3.11 (3H, s) , 4.76 (2H, br s), 5.23 (2H, br s), 6.78-6.93 (2H, m) , 7.21-7.54 (9H, m)
Example 71
. To a solution of 1.5 g of 1- (2, 6-difluorobenzoyl) -3- [2-fluoro-4- (trifluoromethylthio) phenyl] -1-methylurea in 7 ml of 1, 3-dimethyl-2-imidazolidinone was added 758 mg of 2- chloroethyl chloromethyl ether at 0°C, and then, 189 mg of sodium hydride (content; 55% by weight ion oil) was added thereto. The resulting mixture was stirred at room
temperature for 1 hour. To the reaction mixture were added 10 ml of an aqueous saturated ammonium chloride solution and 20 ml of ethyl acetate, and the mixture was stirred for 30 minutes. This mixture was filtered through Celite. The filtrate was washed sequentially with water and an aqueous saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The resulting residue was purified by medium pressure preparative high performance liquid chromatography (ethyl acetate :hexane = 25:75) to obtain 882 mg of 3- (2- chloroethoxymethyl) -1- (2, 6-difliorobenzoyl )-3-[2-fluoro-4- (trifluoromethylthio) phenyl] -1-methylurea (hereinafter, referred to as present compound (71) ) .
Present compound (71)
Figure imgf000271_0001
1H-NMR (DMSO-d6, measuring temperature : 8O0C) δ (ppm) : 3.05 (3H, s) , 3.68 (2H, t, J = 5.4 Hz) , 3.84 (2H, t, J = 5.4 Hz) , 5.18 (2H, s) , 7.03-7.14 (2H, m) , 7.46-7.61 (3H, m) , 7.66- 7.74 (IH, m) .
Production Example 11
To 5.09 g of 2-fluoro-N- (2-hydroxyethyl) -A- (trifluoromethylthio) aniline was added 30 ml of 3,4- dihydro-2H-pyran, and 500 mg of pyridinium p- toluenesulfonate monohydrate was added thereto under ice- cooling. The resulting mixture was stirred at room temperature for 1 hour. To the reaction mixture was added 100 ml of tert-butyl methyl ether, and the resulting mixture was washed sequentially with water and an aqueous saturated sodium chloride solution. The organic layer was dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain 6.77 g of 2-fluoro-N- [2- (2-tetrahydro-2H-pyranyloxy) ethyl] -A-
( trifluormethylthio) aniline . This aniline compound was dissolved in 40 ml of ethyl acetate, to the solution was slowly added a solution of 4.65 g of 2, 6-difluorobenzoyl isocyanate in 10 ml of ethyl acetate, and the mixture was stirred for 30 minutes. This reaction mixture was
concentrated under reduced pressure. The resulting residue was purified by medium pressure preparative high
performance liquid chromatography (ethyl acetate : hexane = 34:66) to obtain 4.16 g of 1- (2, 6-difluorobenzoyl) -3- [2- fluoro-4- (trifluoromethylthio) phenyl] -3- [2- (2-tetrahydro- 2H-pyranyloxy) ethyl] urea .
1- (2, 6-Difluorobenzoyl) -3- [2-fluoro-4- (triflioromethylthio) phenyl] -3- [2- (2-tetrahydro-2H- pyranyloxy) ethyl] urea
Figure imgf000272_0001
1H-NMR (CDCl3 )δ(ppm) : 1.42-1.91 (6H, br m) , 3.48-3.65 (2H, br m) , 3.76-4.06 (4H, br m) , 4.59-4.76 (1IH, br m) , 6.91 (2H, t, J = 8.3 Hz), 7.29-7.54 (5H, m)
Production Example 12
To a solution of 4.0 g of 1- (2, 6-difluorobenzoyl) -3-
[2-fluoro-4- (trifluoromethythio) phenyl] -3- [2- (2-tetrahydro- 2H-pyranyloxy) ethyl] urea in 45 ml of 1, 3-dimethyl-2- imidazolidinone was added 2.17 g of methyl iodide, and then, 330 mg of sodium hydride (content; 55% by weight in oil) was added thereto under ice-cooling. The resulting mixture was stirred at room temperature for 1 hour. To the
reaction mixture were added 30 ml of an aqueous saturated ammonium chloride solution and 30 ml of ethyl acetate, the mixture was stirred for 30 minutes, 150 ml of ethyl acetate was added thereto, and the mixture was separated into layers. The organic layer was washed sequentially with water and an aqueous saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The resulting residue was purified by medium pressure preparative high performance liquid chromatography (ethyl acetate : hexane =25:75) to obtain 367 g of 1- (2, 6-difluorobenzoyl) -3- [2-fluoro-4- (trifluoromethylthio) phenyl] -3- [2- [2-tetrahydro-2H- pyranyloxy] ethyl] -1-methylurea.
1- (2, 6-Difluorobenzoyl) -3- [2-fluoro-4- (trifluoromethylthio) phenyl] -3- [2- [2-tetrahydro-2H- pyranyloxy] ethyl] -1-methylurea
Figure imgf000274_0001
1H-NMR (DMSO-Cl6, measuring temperature : 80°C) δ (ppm) 1.30- 1.58 (6H, m) , 3.00 (3H, s), 3.31-3.40 (IH, m) , 3.49-3.65
(2H, m) , 3.72-3.97 (3H, m) , 4.41-4.47 (IH, m) , 7.08 (2H, t, J = 8.3 Hz), 7.42 (IH, t, J = 8.2 Hz), 7.48-7.58 (2H, m) , 7.66 (IH, dd, J = 10.1, 1.9 Hz)
Production Example 13
To a solution of 3.67 g of 1- (2, 6-difluorobenzoyl) -3- [2-fluoro-4- (trifluoromethylthio) phenyl] -3- [2- (2- tetrahydro-2H-pyranyloxy) ethyl] -1-methylurea in 40 ml of methanol was added 30 ml of 2N hydrochloric acid, and the resulting mixture was stirred at room temperature for 30 minutes. To this reaction mixture was added an aqueous saturated sodium bicarbonate solution to neutralize it, followed by extraction with ethyl acetate three times. The organic layer was washed with an aqueous saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The resulting residue was purified by medium pressure preparative high performance liquid chromatography (ethyl acetate : hexane = 34:66), and was further purified by high performance liquid chromatography to obtain 800 mg of 1- (2 , 6-difluorobenzoyl )λ-
3- [2-fluoro-4- (trifluoromethylthio) phenyl] -3- (2- hydroxyethyl) -1-methylurea .
1- (2, 6-Difluorobenzoyl) -3- [2-fluoro-4-
(trifluoromethylthio) phenyl] -3- (2-hydroxyethyl) -1- methylurea.
Figure imgf000275_0001
suring temperature : 800C) δ (ppm) : 3.01 (3H, Ns), 3.53 (2H, q, J = 5.7 Hz), 3.72 (2H, t, J = 5.7 Hz), 4.52 (IH, t, J = 5.7 Hz), 7.07 (2H, t, J = 8.4 Hz), 7.43 (IH, t, J = 8.4 Hz), 7.48-7.57 (2H, m) , 7.65 (IH, dd, J = 10.0, 2.0 Hz)
Example 72
To a solution of 400 mg of 1- (2, 6-difluorobenzoyl) -3- [2-fluoro-4- (trifluoromethylthio) phenyl] -3- (2- hydroxyethyl) -1-methylurea in 5 ml of ethyl acetate was added 107 mg of triethylamine, and then, 69 mg of acetyl chloride was added thereto. The resulting mixture was stirred at room temperature for 30 minutes. To this
reaction mixture was added 20 ml of tert-butyl methyl ether and 10 ml of hexane, and the mixture was filtered through Celite. The filtrate was concentrated under reduced pressure. The resulting residue was purified by medium pressure preparative high performance liquid chromatography (ethyl acetate : hexane =34:66) to obtain 180 mg of 3- (2- acetoxyethyl) -1- (2, 6-difluorobenzoyl) -3- [2-fluoro-4- (trifluoromethylthio) phenyl] -1-methylurea (hereinafter, referred to as present compound (72)).
Present compound (72)
Figure imgf000276_0001
1H-NMR (CDCl3 )δ(ppm) : 1.84 (3H, s) , 3.06 (3H, s) , 3.87-4.11 (2H, br m) , 4.24-4.41 (2H, br m) , 6.78-6.98 (2H, br m) ,
7.21-7.70 (4H, m)
Production Example 14
-To a solution of 1.00 g of 2-fluoro-N-methoxymethyl-4-
(trifluoromethylthio) aniline in 10 ml of toluene was added 0.55 ml of triethylamine . To the mixture was added
dropwise a solution of 1.20 g of
bis (trichloromethyl) carbonate in 5 ml of toluene at 1°C to
8°C. The resulting mixture was stirred for 1 hour. The reaction mixture was concentrated under reduced pressure, 20 ml of an aqueous saturated sodium bicarbonate solution and 20 ml of chloroform were added, and the mixture was separeted into layers. The organic layer was dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The resulting residue was dissolved in 20 ml of acetonitrile, and 2.00 ml of a 33% methylamine-ethanol solution was added thereto. The resulting mixture was stirred at room temperature for 20 minutes. The reaction mixture was concentrated under reduced pressure. To the residue were added 20 ml of water and 20 ml of chloroform, and the mixture was separated into layers.' The organic layer was dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain the residue, which was purified by silica gel chromatography (ethyl acetate : hexane =1:1) to obtain 0.38 g of 1- [2-fluoro-4- ( trifluoromethylthio) phenyl] -l-methoxymethyl-2-methylurea . 1- [2-Fluoro-4- (trifluoromethylthio) phenyl] -1-methoxymethyl- 2-methylurea
Figure imgf000277_0001
1H-NMR(CDCl3)S(PPm): 2.82 (3H,m) , 3.42(3H,s), 4.76(lH,br), 4.99(2H,s), 7.36-7.40 (IH, m) , 7.48-7.50 (2H,m)
Example 21- (1)
To a solution of 0.38 g of 1- [2-fluoro-4-
(trifluoromethylthio) phenyl] -l-methoxymethyl-3-methylurea in 3.0 ml of pyridine was added 0.17 ml of 2,6- difluorobenzoyl chloride. The resulting mixture was stirred at room temperature for 5 days. ' The reaction mixture was added to 10 ml of water, and 10 ml of ethyl acetate, ,and the mixture was separated into layers. The organic layer was washed sequentially with 10 ml of 7% hydrochloric acid, 10 ml of water and 10 ml of an aqueous saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The resulting residue was subjected to silica gel
chromatography purification (ethyl acetate : chloroform:
hexane = 1:1:4) to obtain 0.18 g of l-(2,6- difluorobenzoyl) -3- [2-fluoro-4-
(trifluoromethylthio) phenyl] -3- (methoxymethyl) -1-methylurea (present compound (21) ) .
Preparation Example 15
To a solution of 3.0 g of 2-fluoro-N-methoxymethyl-4- (trifluoromethylthio) aniline in 30 ml of toluene was added 1.8 ml of triethylamine, and then, 1.57 g of
bis (trichloromethyl) carbonate was added thereto. This reaction mixture was stirred at 50°C for 3 hours, and the temperature was returned to room temperature. To this reaction mixture was added 2.8 ml of triethylamine, then, 1.8 g of allylamine was added, and the mixture was stirred at room temperature for 16 hours. To this reaction mixture was added 80 ml of ethyl acetate, and the mixture was washed sequentially with water, an aqueous saturated sodium bicarbonate solution, and aqueous saturated sodium chloride solution. The organic layer was dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The resulting residue was purified by medium pressure preparative high performance liquid chromatography
(hexane : ethyl acetate = 75:25) to obtain 1.74 g of 3-allyl- 1- [2-fluoro-4- (trifluoromethylthio) phenyl] -1- methoxymethylurea .
3-Allyl-l- [2-fluoro-4- (trifluoromethylthio) phenyl] -1- methoxymethylurea
Figure imgf000279_0001
1H-NMR (CDCl3) δ (ppm) : 3.43 (3H, s) , 3.88 (2H, tt, J = 5.6, 1.6 Hz), 4.83-4.92 (IH, br m) , 5.01 (2H, s) , 5.07-5.18 (2H, m) , 5.79-5.90 (IH, m) , 7.39 (IH, t, J = 8.0 Hz), 7.47-7.53 (2H, m)
Example 73
To a solution of 1.55 g of 3-allyl-l- [2-fluoro-4- (trifluoromethylthio) phenyl] -1-methoxymethylurea and 2.0 ml of diisopropylethylamine in 20 ml of toluene was added 1.61 g of 2, 6-difluorobenzoyl chloride, and the resulting mixture was stirred for 3 hours under heat refluxing. This reaction mixture was cooled to room temperature, 80 ml of tert-butyl methyl ether was added, and this was washed sequentially with water, an aqueous saturated sodium
bicarbonate solution, and an aqueous saturated sodium chloride solution. The organic layer was dried over
anhydrous magnesium sulfate, and concentrated under reduced pressure. The resulting residue was purified by medium pressure preparative high performance liquid chromatography (hexane:ethyl acetate = 90:10) to obtain 1.38 g of 1-allyl- 1- (2, 6-difluorobenzoyl) -3- [2-fluoro-4- ( trifluoromethylthio) phenyl] -3-methoxymethylurea
(hereinafter, referred to as present compound (73)).
Present compound (73)
Figure imgf000280_0001
1H-NMR (DMSO-d6, measuring temperature: 80°C) δ (ppm) : 3.33 (3H, s) , 4.09 (2H, d, J = 5.6 Hz) , 4.95-5.10 (4H, m) , 5.71-5.84
(IH, m) , 7.08 (2H, t, J = 8.9 Hz) , 7.44 (IH, t, J = 8.1 Hz) ,
7.49-7.59 (2H, m) , 7.69 (IH, d, J = 9.9 Hz)
Production Example 16
To a solution of 3.0 g of 2-fluoro-N-methoxymethyl-4- (trifluoromethylthio) aniline in 30 ml of toluene was added
1.8 ml of triethylamine, and then, 1.57 g of
bis (trichloromethyl) carbonate was added thereto. This reaction mixture was stirred at 50°C for 3 hours, and the temperature was returned to room temperature. To this reaction mixture was added 2.8 ml of triethylamine, then, 780 mg of propargylamine was added, and the mixture was stirred at room temperature for 16 hours. To the reaction mixture was added 80 ml of ethyl acetate, and this was washed sequentially with water, an aqueous saturated sodium bicarbonate solution, and an aqueous saturated sodium chloride solution. The organic layer was dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The resulting residue was purified by medium pressure preparative high performance liquid chromatography (hexanerethyl acetate = 75:25) to obtain 1.80 g of 1- [2- fluoro-4- (trifluoromethylthio) phenyl] -l-methoxymethyl-3- propargylurea .
1- [2-Fluoro-4- (trifluoromethylthio) phenyl] -1-methoxymethyl- 3-propargylurea
Figure imgf000281_0001
1H-NMR (CDCl3) δ (ppm) : 2.22 (IH, t, J = 2.7 Hz), 3.43 (3H, s), 4.04 (IH, d, J = 2.7 Hz), 4.05 (IH, d, J = 2.7 Hz), 4.94-5.09 (IH, br) , 5.00 (2H, s), 7.38 (IH, t, J = 8.0 Hz), 7.46-7.55 (2H, m)
Example 74
To a solution of 1.50 g of 1- [2-fluoro-4- (trifluoromethylthio) phenyl] -l-methoxymethyl-3- propargylurea and 2.0 ml of diisopropylethylamine in 20 ml of toluene was added 1.57 g of 2, 6-diflurobenzoyl chloride, and the resulting mixture was stirred for 3 hours under heat refluxing. This reaction mixture was cooled to room temperature, and 80 ml of tert-butyl methyl ether was added. This was washed sequentially with water, an aqueous
saturated sodium bicarbonate solution, and ' an aqueous saturated sodium chloride solution. The organic layer was dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The resulting residue was purified by medium pressure preparative high performance liquid chromatography (hexane : ethyl acetate = 90:10) to obtain 631mg of 1- (2, 6-difluorobenzoyl) -3- [2-fluoro-4- (trifluoromethylthio) phenyl] -3-methoxymethyl-l- propargylurea (hereinafter, referred to as present compound (74) ) .
Present Compound (74)
Figure imgf000282_0001
1H-NMR (DMSO-d6, measuring temperature : 800C) δ (ppm) : 3.08 (IH, t, J = 2.4 Hz), 3.33 (3H, s), 4.32 (2H, d, J = 2.4 Hz), 5.04 (2H, s), 7.10 (2H, t, J = 8.5 Hz), 7.45 (IH, t, J = 8.2 Hz), 7.51-7.61 (2H, m) , 7.66 (IH, dd, J = 10.1, 1.9 Hz) Production Example 17
To a solution of 20 ml of toluene was dissolved 2.O g of 2-fluoro-N-methoxymethyl-4- (trifluoromethylthio) aniline was added 1.2 ml of triethylamine, and then, 1.05 g of bis (trichloromethyl) carbonate was added thereto. This reaction mixture was stirred at 5O0C for 3 hours, and the temperature was returned to room temperature. To this reaction mixture was added 1.9 ml of triethylamino, then, 1.3 g of 2-phenoxyethylamino was added, and the mixture was stirred at room temperature for 16 hours. To this reaction mixture was added 80 ml of ethyl acetate, and this was washed sequentially with water, an aqueous saturated sodium bicarbonate solution, and an aqueous saturated sodium chloride solution. The organic layer was dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The resulting 'residue was purified by medium pressure preparative high performance liquid chromatography (hexane:ethyl acetate = 75:25) to obtain 1.30 g of l-[2- fluoro-4- (trifluoromethylthio) phenyl] -l-methoxymethyl-3- (2- phenoxyethyl) urea.
1- [2-Fluoro-4- (trifluoromethylthio) phenyl] -1-methoxymethyl-
3- (2-phenoxyethyl) urea
Figure imgf000283_0001
1H-NMR (CDCl3) δ (ppm) : 3.40 (3H, s), 3.64 (2H, q, J = 5.2 Hz), 4.05 (2H, t, J = 5.2 Hz), 4.99 (2H,' s) , 5.24-5.33 (IH, br m) , 6.82 (2H, d, J = 7.7 Hz), 6.97 (IH, t, J = 7.4 Hz), 7.25-7.31 (2H, m) , 7.35 (IH, t, J = 8.1 Hz), 7.43-7.50 (2H, m)
Example 75
To a solution of 1.10 g of 1- [2-fluoro-4- (trifluoromethylthio) phenyl] -l-methoxymethyl-3- (2- phenoxyethyl) urea and 1.1 ml of diisopropylethylamine in 20 ml of toluene was added 928 mg of 2, β-difluorobenzoyl chloride, and the resulting mixture was stirred for 3 hours under) heat refluxing. This reaction mixture was cooled to room temperature, 80 ml of tert-butyl methyl ether was added, and this was washed sequentially with water, an aqueous saturated sodium bicarbonate solution, and an aqueous saturated sodium chloride solution. The organic layer was dried with anhydrous magnesium sulfate, and concentrated under reduced pressure. The resulting residue was purified by medium pressure preparative high
performance liquid chromatography (hexane : ethyl acetate = 90:10) to obtain 786 mg of 1- (2, 6-difliorobenzoyl) -3- [2- fluoro-4- (trifluoromethylthio) phenyl] -3-methoxymethyl-l- (2- phenoxyethyl) urea (hereinafter, referred to as present compound (75) ) .
Present compound (75)
Figure imgf000285_0001
1H-NMR (DMSO-de, measuring temperature : 80°C) δ (ppm) : 3.31 (3H, s), 3.90 (2H, t, J = 5.4 Hz), 4.18 (2H, t, J = 5.4 Hz),
5.05 (2H, s), 6.83 (2H, d, J = 8.4 Hz), 6.93 (IH, t, J = 7.4 Hz), 7.08 (2H, t, J = 8.5 Hz), 7.25 (2H, dd, J = 8.4,
7.4 Hz), 7.45 (IH, t, J = 8.1 Hz), 7.49-7.57 (2H, m) , 7.64 (IH, dd, J = 10.0, 1.8 Hz)
Production example 18
To a solution of 6.0 g of 2-fluoro-N-methoxymethyl-4- (trifluoromethylthio) aniline in 60 ml of toluene was added
3.6 ml of triethylamine, and then, 3.14 g of
bis (trichloromethyl) carbonate was added thereto. This reaction mixture was stirred at 50°C for 3 hours, and the temperature was returned 'to' room temperature. To this reaction mixture was added 5.6 ml of triethylamine and, then, 2.58 g of 2-methylthioethylamine, and the mixture was stirred at room temperature for 16 hours. To this reaction mixture was added 150 ml of ethyl acetate, and this was washed sequentially with water, an aqueous saturated sodium bicarbonate solution, and an aqueous saturated sodium chloride solution. The organic layer was dried over
anhydrous magnesium sulfate, and concentrated under reduced pressure. The resulting residue was purified by medium pressure preparative high performance liquid chromatography (hexanerethyl acetate = 75:25) to obtain 3.70 g of l-[2- fluoro-4- (trifluoromethylthio) phenyl] -l-methoxymethyl-3- (2- methylthioethyl) urea.
1- [2-Fluoro-4- (trifluoromethylthio) phenyl] -1-methoxymethyl-
3- (2-methylthioethyl) urea
Figure imgf000286_0001
1H-NMR (CDCl3) δ (ppm) : 2.07 (3H, s) , 2.64 (2H, t, J = 6.3 Hz), 3.42 (3H, s), 3.44 (2H, q, J = 6.3 Hz), 5.00 (2H, s), 5.19-5.29 (IH, br m) , 7.40 (IH, t, J = 7.8 Hz), 7.47-7.53 (2H, m)
Example 76
To a solution of 3.45 g of 1- [2-fluoro-4- ( trifluoromethylthio) phenyl] -l-methoxymethyl-3- (2- methylthioethyl) urea and 4.0 ml of diisopropylethylamine in 50 ml in toluene was added 3.27 g of 2 , 6-difluorobenzoyl chloride, and the resulting mixture was stirred for 3 hours under heat refluxing. This reaction mixture was cooled to room temperature, 80 ml of tert-butyl methyl ether was added thereto, and this was washed sequentially with water, an aqueous saturated sodium bicarbonate solution, and an aqueous saturated sodium chloride solution. The organic layer was dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The resulting residue was purified by medium pressure preparative high
performance liquid chromatography (hexane : ethyl acetate = 90:10) to obtain 3.37 g of 1- (2, 6-difluorobenzoyl) -3- [2- fluoro-4- (trifluoromethylthio) phenyl] -3-methoxymethyl-l- (2- methylthioethyl) urea (hereinafter, referred to as present compound (76) ) .
Present compound (76)
Figure imgf000287_0001
1H-NMR (DMSO-d6, measuring temperature : 800C) δ (ppm) : 1.92 (3H, s) , 2.68 (2H, t, J = 7.6 Hz) , 3.32 (3H, s) , 3.68 (2H, t, J = 7.6 Hz) , 5.02 (2H, s) , 7.11 (2H, t, J = 8.5 Hz) , 7.41 (IH, t, J = 8.2 Hz) , 7.51-7.61 (2H, m) , 7.69 (IH, dd, J = 10.0, 1.8 Hz)
Examples 77 and 78
A solution of 2.84 g of 1- (2, 6-difluorobenzoyl) -3- [2- fluoro-4- (trifluoromethylthio) phenyl] -3-methoxymethyl-l- (2- methylthioethyl) urea in 50 ml of chloroform was ice-cooled to 5°C, 2.06 g of m-chloroperbenzoic acid (65% by weight) was added thereto, and the mixture was stirred at room temperature for 1 hour. This reaction mixture was washed sequentially with water, an aqueous saturated sodium
bicarbonate solution, and an aqueous saturated sodium chloride solution. The organic layer was dried over
anhydrous magnesium sulfate, and concentrated under reduced pressure. The resulting residue was purified by medium pressure preparative high performance liquid chromatography (hexane: ethyl acetate = 50:50) to obtain 1.47 g of l-(2,6- difluorobenzoyl) -3- [2-fluoro-4- (trifluoromethylthio) - phenyl] -3-methoxymethyl-l- (2-methylsulfinylethyl) urea
(hereinafter, referred to as present compound (77)) and 1.40 g of 1- (2, 6-diflurobenzoyl) -3- [2-fluoro-4- (trifluoromethylthio) phenyl] -3-methoxymethyl-l- (2- methylsulfonylethyl) urea (hereinafter, referred to as present compound (78)).
Present compound (77)
Figure imgf000288_0001
1H-NMR (DMSO-d6, measuring temperature : 800C) δ (ppm) : 2.54 (3H, s) , 2.86-2.95 (IH, m) , 3.06-3.14 (IH, m) , 3.31 (3H, s) , 3.88-4.00 (2H, m) , 5.01 (2H, s) , 7.11 (2H, t, J = 8.5 Hz) , 7.37 (IH, t, J = 8.2 Hz) , 7.52-7.62 (2H, m) , 7.69 (IH, dd, J = 10.1, 1.9 Hz)
Present compound (78)
Figure imgf000288_0002
1H-NMR (DMSO-de, measuring temperature : 800C) δ (ppm) : 3.00 (3H, s) , 3.30 (3H, s) , 3.43 (2H, t, J = 7.6 Hz) , 4.00 (2H, t, J = 7.6 Hz) , 5.00 (2H, s) , 7.12 (2H, t, J = 8.5 Hz) , 7.32 (IH, t, J = 8.*2 Hz) , 7.52-7.63 (2H, m) , 7.69 (IH, dd, J = 10.1, 1.9 Hz)
Production example 19
To a solution of 3.0 g of 2-fluoro-N-methoxymethyl-4- (trifluoromethylthio) aniline in 30 ml of toluene was added 1.8 ml of triethylamine, and then, 1.57 g of
bis (trichloromethyl) carbonate was added thereto. This reaction mixture was stirred at 500C for 3 hours, and the temperature was returned to room temperature. To this reaction mixture were added 2.8 ml of triethylamine and, then, 1.24 g of N, N-dimethylethylenediamine, and the
mixture was stirred at room temperature for 16 hours. To this- reaction mixture was added 80 ml of ethyl acetate, and this was washed sequentially with water, an aqueous
saturated sodium bicarbonate solution, and an aqueous saturated sodium chloride solution. The organic layer was dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The resulting residue was purified by medium pressure preparative high performance liquid chromatography (ethyl acetate imethanol = 90:10) to obtain 1.89 g of 3- (2-dimethylaminoethyl) -1- [2-fluoro-4- (trifluoromethylthio) phenyl] -1-methoxymethylurea . 3- (2-dimethylaminoethyl) -1- [2-fliuoro-4-
(trifluoromethylthio) phenyl] -1-methoxyme'thylurea
Figure imgf000290_0001
1H-NMR (CDCl3) δ (ppm) : 2.13 (6H, s), 2.35 (2H, t, J = 6.1 Hz), 3.29 (2H, td, J = 6.1, 5.0 Hz), 3.42 (3H, s) , 5.01 (2H, s), 5.29-5.42 (IH, br m) , 7.40 (IH, t, J = 8.0 Hz), 7.49 (2H, d, J = 8.0 Hz)
Example 79
To a solution of 1.67 g of 3- (2-dimethylaminoethyl) -1- [2-fluoro-4- (trifluoromethylthio) phenyl] -1- methoxymethylurea and 2.0 ml of diisopropylethylamine in 20 ml of toluene was added 1.60 g of 2, 6-difluorobenzoyl chloride. The resulting mixture was stirred for 3 hours under heat refluxing. After this reaction mixture was cooled to room temperature, 80 ml of tert-butyl methyl ether was added, and this was washed sequentially with water, an aqueous saturated sodium bicarbonate solution, and an aqueous saturated sodium chloride solution. The organic layer was dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The resulting residue was purified by medium pressure preparative high performance liquid chromatography (ethyl acetate) to obtain 1.81 g of 1- (2-dimethylaminoethyl) -1- (2, 6-difluorobenzoyl) - 3- [2-fluoro-4- (trifluoromethylthio) phenyl] -3- methoxymethylurea (hereinafter, referred" to as present compound (79) ) .
Present compound (79)
Figure imgf000291_0001
1H-NMR (DMSO-d6, measuring temperature : 80°C) δ (ppm) : 2.05 (6H, s), 2.47 (2H, t, J = 6.8 Hz), 3.32 (3H, s), 3.55 (2H, t, J = 6.8 Hz), 5.02 (2H, s) , 7.09 (2H, t, J = 8.5 Hz), 7.46- 7.58 (3H, m) , 7.67 (IH, dd, J = 10.1, 1.9 Hz)
Production example 20
To a solution of 3.0 g of 2-fluoro-N-methoxymethyl-4- (trifluoromethylthio) aniline in 30 ml of toluene was added 1.8 ml of triethylamine, and then, 1.57 g of
bis (trichloromethyl) carbonate was added thereto. This mixture was stirred at room temperature for 3 hours. To this mixture was added 2.7 ml of triethylamine, then, 0.77 g of 1-propylamine was added, and the mixture was stirred at room temperature for 1 hour. This reaction mixture was washed sequentially with 50 ml of water and 50 ml of an aqueous saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The resulting residue was subjected to silica gel chromatography purification (ethyl acetate : hexane = 1:2 to 1:1) to obtain 2.05 g of 1- [2-fluoro-4-
( trifluoromethylthio) phenyl] -l-methoxymethyl-3-propylurea .
1- [2-Fluoro-4- (trifluoromethylthio) phenyl] -1-methoxyτnethyl-
3-propylurea
Figure imgf000292_0001
1H-NMR (CDCl3)δ(ppm) : 0.87-0.94 (3H, m) , 1.48-1.57 (2H, m) , 3.18-3.23 (2H, m) , 3.42 (3H, s), 4.81(1H, br) , 4.99 (2H, s), 7.36-7.40 (IH, m) , 7.48-7.50 (2H, m)
Example 80
"iTo a solution of 1.00 g of 1- [2-fluoro-4-
(trifluoromethylthio) phenyl] -l-methoxymethyl-3-propylurea and 0.61 ml of diisopropylethylamine in 10 ml of toluene was added 0.41 ml of 2, 6-difluorobenzoyl chloride, and the resulting mixture was stirred for 8 hours under heat
refluxing. This reaction mixture was cooled to room
temperature, and washed with 10 ml of water. The organic layer was dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The resulting residue was subjected to silica gel chromatography purification (ethyl acetate : hexane = 1:5) to obtain 0.42 g of l-(2,6- difluorobenzoyl) -3- [2-fluoro-4-
(trifluoromethylthio) phenyl] -3-methoxymethyl-l-propylurea (hereinafter, referred to as present compound (80) ) . Present compound (80)
Figure imgf000293_0001
1H-NMR (DMSO-d6, measuring temperature : 80°C) δ (ppm) : 0.76-
0.80 (3H, m), 1.56-1.60 (2H, m) , 3.31 (3H, s) , 3.41-3.45 (2H, m) , 5.01 (2H, s), 7.08-7.12 (2H, m) , 7.42-7.44 (IH, m) , 7.54-7.58 (2H, m) , 7.68-7.71 (IH, m)
Production Example 21
To a solution of 3.0 g of 2-fluoro-N-methoxymethyl-4- (trifluoromethylthio) aniline in 30 ml of toluene was added 1.8 ml of triethylamine, and then, 1.57 g of
bis (trichloromethyl) carbonate was added thereto. This reaction mixture was stirred at 5O0C for 3 hours, and the temperature was returned to room temperature. To this reaction mixture were added 2.8 ml of triethylamine, and then, 1.4 ml of benzylamine, and the mixture was stirred at room temperature for 1 hour. This reaction mixture was washed sequentially with 50 ml of water and 50 ml of an aqueous saturated sodium chloride solution. The organic layer was dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The resulting residue was subjected to silica gel chromatography purification (ethyl acetate :hexane = 1:2 to obtain 2.00 g of 3-benzyl-l- [2-fluoro-4- (trifluoromethylthio) phenyl] -1- methoxymethylurea .
3-Benzyl-l- [2-fluoro-4- (trifluoromethylthio) phenyl] -1- methoxymethylurea
Figure imgf000294_0001
1H-NMR (CDCl3) δ (ppm) : 3.43 (3H, s) , 4.38-4.46 (2H, m) , 5.03
(2H, s) , 5.15 (IH, br) , 7.26-7.49 (8H, m)
Example 81
To a solution of 2.00 g of 3-benzyl-l- [2-fluoro-4-
(trifluoromethylthio) phenyl] -1-methoxymethylurea and 1.8 ml of dMsopropylethylamine in 20 ml of toluene was added 1.3 ml of 2, 6-difluorobenzoyl chloride, and the resulting mixture was stirred for 3 hours under heat refluxing.
After cooled to room temperature, the reaction mixture was washed with 20 ml of water. The organic layer was dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The resulting residue was subjected to silica gel chromatography purification (ethyl
acetate : hexane = 1:5) to obtain 0.57 g of 1-benzyl-l- (2, 6- difluorobenzoyl) -3- [2-fluoro-4- (trifluoromethylthio) phenyl] -3-methoxymethylurea
(hereinafter, referred to as present compound (81)).
Present compound (81)
Figure imgf000295_0001
1H-NMR (DMSO-d6, measuring temperature : 80°C) δ (ppm) : 3.27 (3H, s), 4.72 (2H, s), 5.02 (2H, s) , 6.99-7.03 (2H, m) , 7.20- 7.31 (6H, m) , 7.47-7.53 (2H, m) , 7.65-7.67 (IH, m)
Example 82
To a solution of 1.01 g of 1- (2, 6-difluorobenzoyl) -3- [2, 5-difluoro-4- (trifluoromethylthio) phenyl] urea in 10.0 ml of l-methyl-2-pyrolidone were added 0.61 ml of chloromethyl methyl ether and 243 mg of sodium hydride (content; 55% by weight in oil) at 2°C under ice-cooling, and the resulting mixture was stirred for 4 hours under ice-cooling. To the reaction mixture was added a mixture of 10 ml of an aqueous saturated ammonium chloride solution and 5 ml of water under ice-cooling, followed by extraction with 10 ml of ethyl acetate three times. The organic layers were
combined, washed with an aqueous saturated sodium chloride solution three times, dried over anhydrous magnesium
sulfate, and concentrated under reduced pressure. The resulting residue was purified by silica gel column
chromatography purification (ethyl acetate : chloroform:
hexane = 1:1:4) to obtain 0.93 g of l-(2,6- difluorobenzoyl) -3- [2, 5-difluoro-4- (trifluoromethylthio) phenyl] -1, 3-bis (methoxymethyl) urea (hereinafter, referred to as present compound (82)).
Present compound (82)
Figure imgf000296_0001
1H-NMR(CDCl3 )δ(ppm) : 3.37(3H,s), 3.54(3H,s), 4.83 (2H, brs) , 5.14 (2H, brs) , 6.84-6.88 (2H,m) , 7.29-7.39 (2H,m) , 7.45- 7.49(lH,m)
Example 83
To a solution of 1.01 g of 1- (2, 6-difluorobenzoyl) -3- [2, 6-difluoro-4- (trifluoromethylthio) phenyl] urea in 10.-0 ml of l-methyl-2-pyrrolidone were added 0.61 ml of
chloromethyl methyl ether and 243 mg of sodium hydride (content; 55% by weight in oil) at 2°C under ice-cooling, ant the resulting mixture was stirred for 4 hours under ice-cooling. To the reaction mixture was added a mixture of 10 ml of an aqueous saturated ammonium chloride solution and 5 ml of water under ice-cooling, followed by extraction with 10 ml of ethyl acetate three times. The organic layers were combined, washed with an aqueous saturated sodium chloride solution three times, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography purification (ethyl acetate : chloroform:
hexane = 1:1:4) to obtain 0.59 g of l-(2,6- difluorobenzoyl) -3- [2, 6-difluoro-4-
(trifluoromethylthio) phenyl] -1, 3-bis (met'hoxymethyl) urea (hereinafter, referred to as present compound (83)).
Present compound (83)
Figure imgf000297_0001
1H-NMR(CDCl3)O(PPm): 3.40 (3H, brs) , 3.48 (3H,'brs) ,
4.85 (2H,brs) , 5.19 (2H, brs) , 6.83-6.87 (2H,m) , 7.29- 7.35(3H,m)
Example 84
^To a solution of 3.01 g of 1- (2, 6-difluorobenzoyl) -3- [2-fluoro-4- (2-propenylthio) phenyl) ] in 30 ml of 1-methyl- 2-pyrrolidone were added 2.1 ml of chloromethyl methyl ether and 819 mg of sodium hydride (content; 55% by weight in oil) at 2°C under ice-cooling, and the resulting mixture was stirred for 4 hours under ice-cooling. To the reaction mixture was added a mixture of 30 ml of an aqueous
saturated ammonium chloride solution and 15 ml of water under ice-cooling, followed by extracted with 30 ml of ethyl acetate. The organic layers were combined, washed with an aqueous saturated sodium chloride solution three times, dried over anhydrous magnesium sulfate, and
concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography purification (ethyl acetate : chloroform: hexane = 1:1:4), and was further purified by medium pressure preparative high performance liquid chromatography (ethyl acetate : hexane = 15:85) to obtain 2.32 g of 1- (2 , 6-difluorobenzoyl) -3- [2- fluoro-4- ( 2-propenylthio) phenyl] -1, 3-bis (methoxymethyl ) urea (hereinafter, referred to as present compound (84)).
Present compound (84)
Figure imgf000298_0001
1H-NMR(CDCl3)O(PPm): 3.38(3H,s), 3.49(3H,s), 3.55- 3.58(^2H,m), 4.82 (2H, brs) , 4.9-5.3 (2H, brs) , 5.08-5.24 (2H,m) , 5.82-5.92 (IH, m) , 6.84-6.88 (2H, m) , 7.05-7.10 (2H,m) ,
7.24(lH,m), 7.31-7.36 (IH, m)
Example 85
To a solution of 0.62 g of 1- (2, 6-difluorobenzoyl) -3- [2-fluoro-4- (2-propenylthio) phenyl] -1, 3- bis (methoxymethyl) urea in 6.0 ml of chloroform was added 0.36 g of m-chloroperbenzoic acid (65% by weight) under ice-cooling, and the mixture was stirred at room
temperature for 0.5 hours. To the reaction mixture was added 6 ml of chloroform, and this was washed with 15 ml of an aqueous sodium bicarbonate solution three times. The organic layer was dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The resulting residue was purified by medium pressure preparative high performance liquid chromatography (ethyl' acetate : hexane =
50:50) to obtain 0.39 g of 1- (2 , 6-difluorobenzoyl) -3- [2- fluoro-4- ( 2-propenylsulfinyl) phenyl] -1,3- bis (methoxymethyl) urea (hereinafter, referred to as present compound (85) )".
Present compound (85)
Figure imgf000299_0001
1H-NMR(CDCl3)O(PPm): 3.38(3H,s), 3.47-3.60 (5H,m) ,
4.83 (2H,brs) , 4.9-5.4 (2H, brs) , 5.23-5.37 (2H,m) , 5.60-
5.67(lH,m), 6.84(2H,m), 7.29-7.36 (2H,m) , 7.49-7.56 (2H,m) Example 86
To a solution of 1.30 g of 1- (2, 6-difluorobenzoyl) -3- [2-fluoro-4- (2-propenylthio) phenyl] -1,3- bis (methoxymethyl) urea in 26.0 ml of chloroform was added 1.67 g of m-chloroperbenzoic acid (65% by weight) under ice-coolmg, and the mixture was stirred at room
temperature for 2 hours. To the reaction mixture was added 26 ml of chloroform, and this was washed with 50 ml of an aqueous sodium bicarbonate solution three times. The organic layer was dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The resulting residue was purified by medium pressure preparative high performance liquid chromatography (ethyl acetate : hexane =5
0:50) to obtain 1.09 g of 1- (2, 6-difluorbbenzoyl) -3- [2- fluoro-4- (2-propenylsulfonyl) phenyl] -1, 3- bis (methoxymethyl) urea (hereinafter, referred to as present compound (86) ) .
Present compound (86)
Figure imgf000300_0001
1H-NMR(CDCl3 )O(PPm) : 3.38(3H,s) , 3.53(3H,s) , 3.80- 3.82 (2H,m) , 4.83 (2H,brs) , 5.0-5.3 (2H, brs) , 5.17-5.36 (2H,m) , 5.72-5.82 (IH, m) , 6.84-6.87 (2H,m) , 7.31-7.38 (IH, m) , 7.61- 7.68 (3H,m)
Example 87
To a solution of 3.01 g of 1- (2, 6-difluorobenzoyl) -3- [2-fluoro-4- (2-propynylthio) phenyl] urea in 30.0 ml of 1- methyl-2-pyrrolidone were added 2. 1 ml of chloromethyl methyl ether and 866 mg of sodium hydroxide at 20C under ice-cooling, and the resulting mixture was stirred under ice-cooling for 3 hours, and at room temperature for 19 hours. To the reaction mixture was added a mixture of 30 ml of an aqueous saturated ammonium chloride solution and 15 ml of water under ice-cooling, followed by extraction with 30 ml of ethyl acetate three times. The organic layers were combined, washed with an aqueous saturated sodium chloride solution three times, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (ethyl acetate : chloroform: hexane = 1:4:4) 5 and further purified by medium pressure preparative high
performance liquid chromatography (ethyl
acetate: chloroform: hexane =15:15:70) to obtain 0.05 g of 1- (2, β-difluorobenzoyl) -3- [2-fluoro-4- (2- propynylthio) phenyl] -1, 3-bis (methoxymethyl) urea
,10 (hereinafter, referred to as present compound (87)).
Present compound (87)
Figure imgf000301_0001
1H-NMR(CDCl3)O(PPm): 2.25(lH,m), 3.38 (3H, brs) , 3.50 (3H, brs) , 3.61(2H,m), 4.83 (2H, brs) , 5.07 (2H, brs) , 6.85-6.87 (2H,m) ,
15 7.17-7.35(4H,m)
Example 88
To a solution of 1.01 g of 1- [4- (3, 3-dichloro-2- propenylthio) -2-fluorophenyl] -3- (2, 6-difluorobenzoyl) urea in 10.00 ml of l-methyl-2-pyrrolidone were added 0.58 ml of
20 chloromethyl methyl ether and 240 mg of sodium hydroxide at 1°C under ice-cooling, and the resulting mixture was stirred under ice-cooling for 4 hours, and at room
temperature for 19 hours. To the reaction mixture was added a mixture of 10 ml of an aqueous saturated ammonium chloride solution and 5 ml of water under ice-cooling, followed by extraction with 10 ml of ethyl acetate three times. The organic layers were combined, washed with an aqueous saturated sodium chloride solution three times, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (ethyl
acetate : chloroform: hexane =1:1:4) to obtain 0.15 g of l-[4- (3, 3-dichloro-2-propenylthio) -2-fluorophenyl] -3- (2, 6- difluorobenzoyl) -1 , 3-bis (methoxymethyl) urea (hereinafter, referred to as present compound (88)).
Present compound (88)
Figure imgf000302_0001
1H-NMR(CDCl3)O(PPm): 3.38(3H,s), 3.51 (3H, brs) , 3.65-
3.67(2H,m), 4.83 (2H, brs) , 5.08 (2H, brs) , 5.94-5.98 (IH, m) , β.84-6.89(2H,m) , 7.08-7.14 (2H,m) , 7.30-7.37 (2H,m)
Example 89
To a solution of 1.01 g of 3- [2-chloro-4- (pentafluoroethylthio) phenyl] -1- (2 , 6-difluorobenzoyl) urea in 10.0 ml of l-methyl-2-pyrrolidone were added 0.59 ml of chloromethyl methyl ether and 235 mg of sodium hydride at 2°C under ice-cooling, and the resulting mixture was stirred for 3 hours under ice-cooling. To the reaction mixture was added a mixture of 10 ml of an aqueous
saturated ammonium chloride solution and 5 ml of water under ice-cooling, followed by extraction with 10 ml of ethyl acetate three times. The organic layers were
combined, washed with an aqueous saturated sodium chloride solution three times, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The resulting residue was purified by silica gel column
chromatography (ethyl acetate: chloroform: hexane = 1:1:4) to obtain 0.85 g of 1- [2-chloro-4-
(pentafluoroethylthio) phenyl] -3- (2, β-difluorobenzoyl) -1,3- bis (methoxymethyl) urea (hereinafter, referred to as present compound (89) ) .
Present compound (89)
Figure imgf000303_0001
1H-NMR(CDCl3)S(PPm): 3.38 (3H, brs) , 3.60 (3H, brs) ,
4.79 (2H,brs) , 5.49 (2H, brs) , 6.82 (2H, brs) , 7.30-7.34 ( IH, m) , 7.52-7.55(2H,m) , 7.78 (IH, m)
Example 90
To a solution of 1.01 g of 1- (2 , 6-difluorobenzoyl) -3- [2-fluoro-4- (1, 1, 2-trifluoro-2- trifluoromethoxyethylthio) phenyl] urea in 10.0 ml of 1- methyl-2-pyrrolidone were added 0.51 ml of chloromethyl methyl ether and 203 mg of sodium hydride at 2°C under ice- cooling, and the resulting mixture was stirred for 3 hours under ice-cooling. To the reaction mixture was added a mixture of 10 ml of an aqueous saturated ammonium chloride solution and 5 ml of water under ice-cooling, followed by extraction with 10 ml of ethyl acetate three times. The organic layers were combined, washed with an aqueous saturated sodium chloride solution three times, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (ethyl acetate : chloroform: hexane = 1:1:4) to obtain 0.87 g of 1- (2, 6-difluorobenzoyl) -3- [2- fluoro-4- (1, 1, 2-trifluoro-2- trifluoromethoxyethylthio) phenyl] -1, 3- bis (methoxymethyl ) urea (hereinafter, referred to as present compound (90) ) .
Present compound (90)
Figure imgf000304_0001
1H-NMR(CDCl3)O(PPm): 3.37 (3H, brs) , 3.54 (3H, brs) ,
4.82 (2H,brs) , 5.13 (2H, brs) , 5.75-5.90 (IH, m) , β.84(2H,m), 7.30-7.40(lH,m) , 7.42-7.47 (3H,m)
Example 91 To a solution of 1.01 g of 1- [3-chloro-4- (1, 1, 2- trifluoro-2-trifluoromethoxyethoxy) phenyl] -3- (2,6- difluorobenzoyl) urea in 10.0 ml of l-methyl-2-pyrrolidone were added 0.51 ml of chloromethyl methyl ether and 203 mg of sodium hydride at 2°C under ice-cooling, and the
resulting mixture was stirred for 4 hours under ice-cooling. To the reaction mixture was added a mixture of 10 ml of an aqueous saturated ammonium chloride solution and 5 ml of water under ice-cooling, followed by extraction with 10 ml of ethyl acetate three times. The organic layers were combined, washed with an aqueous saturated sodium chloride solution three times, dried over anhydrous magnesium
sulfate, and concentrated under reduced pressure. The resulting residue was purified by silica gel column
chromatography (ethyl acetate : chloroform: hexane = 1:1:4), and was further purified by medium pressure preparative high performance liquid chromatography (ethyl
acetate : hexane = 15:85) to obtain 0.28 g of 1- [3-chloro-4- (1,1, 2-trifluoro-2-trifluoromethoxyethyl) phenyl] -3- (2, 6- difluorobenzoyl) -1, 3-bis (methoxymethyl) urea (hereinafter, referred to as present compound (91)).
Present compound (91)
Figure imgf000305_0001
1H-NMR(CDCl3 )δ(ppm) : 3.34 ( 3H, brs) , 3.49 (3H, brs) ,
4.92 (2H,brs) , 5.09 (2H, brs) , 5.93-6.08 (IH, m) , 6.88- 6.92(2H,m), 7.23-7.25 ( IH, m) , 7.32-7.42 (3H,m)
Example 92
To a solution of 1.01 g of 3- (2, 6-difluorobenzoyl) -1- [2-fluoro-4- (trifluoromethylthio) phenyl] -1- methoxymethylurea in 10.0 ml of l-methyl-2-pyrrolidone was added 109 mg of sodium hydride (content; 55% by weight in oil) at 2°C, the mixture was stirred for 30 minutes, 0.19 ml of acetyl chloride was added at 1°C, and the resulting mixture was stirred at room temperature for 4 hours. The reaction mixture was poured into 10 ml of ice water, followed by extraction with 20 ml of ethyl acetate three times. The organic layers were combined, washed with an aqueous saturated sodium chloride solution three times, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (ethyl
acetate : chloroform: hexane = 1:1:4), and was further
purified by medium pressure preparative high performance liquid chromatography (ethyl acetate : hexane = 15:85) to obtain 0.56 g of 1-acetyl-l- (2, 6-difluorobenzoyl ) -3- [2- fluoro-4- (trifluoromethylthio) phenyl] -3-methoxymethylurea (hereinafter, referred to as present compound (92)).
Present compound (92)
Figure imgf000307_0001
1 H-NMR (DMSO-Ci6, measuring temperature : 80°C) δ (ppm) :
2.32(3H,s), 3.41(3H,s), 5.13 (2H, brs) , 7.04-7.08 (2H,m) , 7.52-7.62 (3H,m) , 7.77-7.80 (lH,m)
Production Example 22
To a solution of 3.30 g of N- (3-chloropropyl) -2- fluoro-4- (trifluoromethylthio) acetoanilide in 15 ml of N, N- dimethylformamide was added 6.0 g of sodium thiomethoxide (15% aqueous solution), and the mixture was stirred at room temperature overnight. To this reaction mixture was added 100 ml of ethyl acetate, and this was washed sequentially with water and an aqueous saturated sodium chloride
solution. The organic layer was dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain 2.83 g of 2-fluoro-N- (3-methylthiopropyl) -4- (trifluoromethylthio) acetoanilide .
2-Fluoro-N- (3-methylthiopropyl) -4- (trifluoromethylthio) acetoanilide
Figure imgf000307_0002
1H-NMR (CDCl3) δ (ppm) : 1.75-1.89 (5H, m) , 2.06 (3H, s) , 2.50 (2H, t, J = 6.9 Hz), 3.62-3.93 (2H, br) , 7.31 (IH, t, J = 8.1 Hz) , 7.49-7.56 (2H, m)
Production Example 23
To a solution of 2.83 g of 2-fluoro-N- (3- raethylthiopropyl) -A- (trifluoromethylthio) acetoanilide in 15 ml of methanol was added 5 ml of concentrated hydrochloric acid, and the resulting mixture was stirred for 3 hours under heat refluxing. After the temperature of the
reaction mixture was returned to room temperature, an aqueous sodium hydroxide solution was added thereto to adjust to pH 9. This solution was extracted with tert- butyl methyl ether. The organic layer was washed with an aqueous saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The resulting residue was purified by medium pressure preparative high performance liquid chromatography (hexane:ethyl acetate = 90:10) to obtain 1.03 g of 2- fluoro-N- (3-methylthiopropyl) -A- (trifluoromethylthio) aniline.
2-Fluoro-N- (3-methylthiopropyl) -A- (trifluoromethylthio) aniline
Figure imgf000308_0001
1H-NMR (CDCl3) δ (ppm) : 1.91-2.00 (2H, m) , 2.13 (3H, s) , 2.62 (2H, t, J = 6.8 Hz) , 3.33 (2H, t, J = 61.8 Hz) , 4.32 (IH, br) , 6.69 (IH, t, J = 8.7 Hz) , 7.22-7.27 (IH, m) , 7.29 (IH, d, J = 8.7 Hz)
Example 93
To a solution of 1.02 g of 2-fluoro-N- (3- methylthiopropyl) -4- (trifluoromethylthio) aniline in 15 ml of tert-butyl methyl ether was added 640 mg of 2,4- difluorobenzoyl isocyanate, and the resulting mixture was stirred at room temperature for 15 minutes. This reaction mixture was concentrated under reduced pressure. The resulting solid was washed with hexane, and dried under reduced pressure to obtain 1.53 g of 3- (2, 6- difluorobenzoyl) -1- [2-fluoro-4- (trifluoromethylthio) phenyl] -1- (3-methylthiopropyl) urea (hereinafter, referred to as present compound (93)).
Present compound (93)
Figure imgf000309_0001
1H-NMR (CDCl3) δ (ppm) : 1.84 (2H, t, J = 7.2 Hz), 2.04 (3H, s), 2.49 (2H, t, J = 7.2 Hz), 3.76 (2H, t, J = 7.2 Hz),
6.94 (2H, t, J = 8.3 Hz), 7.35-7.44 (2H, m) , 7.53-7.60 (2H, m) , 7.62 (IH, br) Example 94
To a solution of 1.42 g of 3- (2, β-'difluorobenzoyl) -1- [2-fluoro-4- (trifluoromethylthio) phenyl] -1- (3- methylthiopropyl) urea in 10 ml of 1, 3-dimethyl-2- imidazolidinone was added 0.37 ml of iodomethane, then, 141 mg of sodium -hydride (60% in oil) was added, and the resulting mixture was stirred at room temperature for 2 hours. To this reaction mixture was added water, followed by extraction with ethyl acetate. The organic layer was washed with an aqueous saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The resulting residue was purified by medium pressure preparative high performance liquid chromatography (hexane: ethyl acetate = 75:25) to obtain 190 mg of 1- (2, 6-difluorobenzoyl) -3- [2-fluoro-4- ( trifluoromethylthio) phenyl] -l-methyl-3- (3- methylthiopropyl) urea (hereinafter, referred to as present compound (94) ) .
Present compound (94)
Figure imgf000310_0001
1H-NMR (DMSO-d6, measuring temperature: 800C) δ (ppm) : 1.71-
1.82 (2H, m) , 1.98 (3H, s) , 2.46 (2H, t, J = 7.2 Hz) , 3.04 (3H, s), 3.75 (2H, t, J = 7.2 Hz), 7.08 (2H, t, J = 8.6 Hz), 7.40 (IH, t, J = 8.3 Hz), 7.48-7.60 (2H; m) , 7.70 (IH, dd, J = 10.1, 1.9 Hz)
Examples 95 and 96
To a solution of 1.99 g of 1- (2, 6-difluorobenzoyl) -3-
[2-fluoro-4- (-trifluoromethylthio) phenyl] -l-methyl-3- (3- methylthiopropyl) urea in chloroform was added 1.49 g of m- chloroperbenzoic acid under ice-cooling, and the mixture was stirred for 30 minutes. To this reaction mixture was added tert-butyl methyl ether, and this was washed
sequentially with an aqueous saturated sodium bicarbonate solution, and an aqueous saturated sodium chloride solution. The organic layer was dried over anhydrous magnesium
sulfate, and concentrated under reduced pressure. The resulting residue was purified by medium pressure
preparative high performance liquid chromatography (ethyl acetate) to obtain 612 mg of 1- (2, 6-difluorobenzoyl) -3- [2- fluoro-4- (trifluoromethylthio) phenyl] -l-methyl-3- [3-
(methylsulfinyl) propyl] urea (hereinafter, referred to as present compound (95)) and 1.21 g of l-(2,6- difluorobenzoyl) -3- [2-fluoro-4-
(trifluoromethylthio) phenyl] -l-methyl-3- [3-
(methylsulfonyl) propyl] urea (hereinafter, referred to as present compound (96)).
Present compound (95)
Figure imgf000312_0001
1H-NMR (DMSO-d6, measuring temperature : 80°C) δ (ppm) : 1.82- 1.93 (2H, m) ,- 2.07 (3H, s) , 2.63 (IH, dt, J = 14.5, 6.6 Hz), 2.77 (IH, dt, J = 14.5, 6.6 Hz), 2.99 (3H, s), 3.75-3.84 (2H, m) , 7.08 (2H, t, J = 8.5 Hz), 7.43 (IH, t, J = 8.3 Hz), 7.48-7.60 (2H, m) , 7.71 (IH, dd, J = 10.1, 1.9 Hz)
Present compound (96)
Figure imgf000312_0002
1H-NMR (DMSOd6, measuring temperautre : 80°C) δ (ppm) : 1.89- 2.00 (2H, m) , 2.91 (3H, -s)., 2.99 (3H, s) , 3.13 (2H, t, J =
7.6 Hz), 3.80 (2H, t, J = 7.6 Hz), 7.08 (2H, t, J = 8.3 Hz), 7.44 (IH, t, J = 8.2 Hz), 7.48-7.60 (2H, m) , 7.72 (IH, dd, J = 10.1, 1.8 Hz)
Production Example 24
To a solution of 4.62 g of N- (3-chloropropyl) -2- fluoro-4- (trifluoromethylthio) aniline in 30 ml of toluene was added 2.24 ml of triethylamine, then, 2.14 g of
bis (trichloromethyl) carbonate was added by portions, and the mixture was stirred at room temperature for 1 hour. To this reaction mixture was added 3 ml of methylamine (40% methanol solution) , and the mixture was' stirred at room temperature for 1 hour. To this reaction mixture was added ethyl acetate, and this was washed sequentially with water and an aqueous saturated sodium chloride solution. The organic layer was dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain 5.52 g of 1- (3-chloropropyl) -1- [2-fluoro-4- (trifluoromethylthio) phenyl] -3-methylurea .
1- (3-Chloropropyl) -1- [2-fluoro-4-
(trifluoromethylthio) phenyl] -3-methylurea
Figure imgf000313_0001
1H-NMR (CDCl3) δ (ppm) : 2.00-2.07 (2H, m) , 2.77 '(3H, d, J =
4.6 Hz), 3.59 (2H, t, J = 6.8 Hz), 3.79 (2H, t, J = 6.8 Hz), 4.16 (IH, d, J = 4.6 Hz), 7.35 (IH, t, J = 8.2 Hz), 7.48-
7.56 (2H, m)
Production Example 25
To a solution of 5.52 g of 1- (3-chloropropyl) -1- [2- fluoro-4- (trifluoromethylthio) phenyl] -3-methylurea in 30 ml of toluene were added 3.36 ml of diisopropylethylamine and
3.40 g of 2, 6-difluorobenzoyl chloride, and the resulting mixture was stirred for 3 hours under heat refluxing. After the temperature of this reaction mixture was returned to room temperature, ethyl acetate was added thereto, and the resulting mixture was washed sequentially with water, an aqueous saturated sodium bicarbonate solution, and an aqueous saturated sodium chloride solution. The organic layer was dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The resulting residue was purified by medium pressure preparative high
performance liquid chromatography (hexane: ethyl acetate = 75:25) to obtain 7.05 g of 1- (3-chloropropyl) -3- (2, 6- difluorobenzoyl) -1- [2-fluoro-4- (trifluoromethylthio) phenyl] -3-methylurea.
1- (3-Chloropropyl) -3- (2, 6-difluorobenzoyl) -1- [2-fluoro-4- (trifluoromethylthio) phenyl] -3-methylurea
Figure imgf000314_0001
1H-NMR (DMSO-d6, measuring temperature : 80°C) δ (ppm) : 1.93- 2.02 (2H, m) , 2.99 (3H, s) , 3.63 (2H, t, J = 6.9 Hz) , 3.79 (2H, t, J = 6.9 Hz) , 7.08 (2H, t, J = 8.4 Hz) , 7.42 (IH, t, J = 8.0 Hz) , 7.48-7.59 (2H, m) , 7.71 (IH, dd, J = 10.0, 2.0 Hz)
Example 97
To a solution of 500 mg of 1- (3-chloropropyl) -3- (2, 6- difluorobenzoyl) -1- [2-fluoro-4-
(trifluoromethylthio) phenyl] -3-methylurea in 2 ml of N, N- dimethylformamide were added 270 mg of morpholine, 514 mg of potassium iodide and 428 mg of potassium carbonate, and the resulting mixture was stirred at 600C for 6 hours. To this reaction mixture was added ethyl acetate, and this was washed sequentially with water, and an aqueous saturated sodium chloride solution. The organic layer was dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The resulting residue was purified by medium pressure preparative high performance liquid chromatography (ethyl acetate) to obtain 509 mg of l-(2,6- difluorobenzoyl) -3- [2-fluoro-4- (trifluoromethylthio) phenyl] -l-methyl-3- (3- morpholinopropyl) urea (hereinafter, referred to as present compound ( 97 ) ) .
Present compound (97)
Figure imgf000315_0001
1H-NMR (DMSO-d6, measuring temperature : 8O0C) δ (ppm) : 1.60- 1.71 (2H, m) , 2.19-2.29 (6H, m) , 2.99 (3H, s) , 3.49 (4H, t,
J = 4.7 Hz) , 3.71 (2H, t, J = 7.2 Hz) , 7.08 (2H, t, J = 8.5 Hz) , 7.40 (IH, t, J = 8.2 Hz) , 7.48-7.58 (2H, m) , 7.69 (IH, dd, J = 10.1, 1.9 Hz)
Example 98
To a solution of 500 mg of 1- (3-chloropropyl) -3- (2, 6- difluorobenzoyl) -1- [2-fluoro-4- (trifluoromethylthio) phenyl] -3-methylurea in 2 ml of N, N- dimethylformamide were added 1 ml of dimethylamine (50% aqueous solution) and 330 mg of potassium carbonate, and the resulting mixture was stirred at 600C 'for 2 hours. To this reaction mixture was added ethyl acetate, and this was washed sequentially with water, and an aqueous saturated sodium chloride solution. The organic layer was dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The resulting residue was purified by medium pressure preparative high performance liquid chromatography (ethyl acetate) to obtain 176 mg of l-(2,6- difluorobenzoyl) -3- (3-dimethylaminopropyl) -3- [2-fluoro-4- (trifluoromethylthio) phenyl] -1-methylurea (hereinafter, referred to as present compound (98)).
Present compound (98)
Figure imgf000316_0001
1H-NMR (DMSO-d6, measuring temperature: 800C) δ (ppm) : 1.55- 1.67 (2H, m) , 2.04 (6H, s) , 2.18 (2H, t, J = 7.1 Hz) , 2.99 (3H, s) , 3.68 (2H, t, J = 7.1 Hz) , 7.08 (2H, t, J = 8.3 Hz) , 7.38 (IH, t, J = 8.2 Hz) , 7.47-7.58 (2H/ m) , 7.69 (IH, dd, J = 10.2, 2.0 Hz)
Then, Preparation Examples will be shown. All "parts" are .by weight.
Preparation Example 1
Ten parts of each of present compounds (1) to (98) is dissolved in a mixture of 35 parts of xylene and 35 parts of N, N-dimethylformamide, and, 14 parts of polyoxyethylene styryl phenyl ether and 6 parts of calcium
dodecylbenzenesulfonate are added thereto. The resulting mixture is thoroughly stirred to obtain a 10% emulsion.
Preparation Example 2
To a mixture of 4 parts of sodium laurylsulfate, 2 parts of calcium ligninsulfonate, 20 parts of a synthetic hydrous silicon oxide fine -powder and 54 ' parts of
diatomaceous earth is added 20 parts of each of present compounds (1) to (98), and the mixture is thoroughly
stirred to obtain a 20% wettable powder.
Preparation Example 3
To 2 parts of each of present compounds (1) to (98) are added 1 part of a synthetic hydrous silicon oxide fine powder, 2 parts of calcium ligninsulfonate, 30 parts of bentonite and 65 parts of kaolin clay, and the mixture is thoroughly stirred. Then, to the resulting mixture is added an appropriate amount of water, the mixture is further stirred, granulated with a granulator, and forced- air dried to obtain 2% granules.
Preparation Example 4
. In an appropriate amount of acetone is dissolved 1 part of each of present compounds (1) to (98), to the solution are added 5 parts of a synthetic hydrous silicon oxide fine powder, 0.3 part of PAP and 93.7 parts of fubasami clay, and the mixture is thoroughly stirred, followed by removal of acetone by evaporation to obtain 1% powder.
Preparation Example 5
A mixture of each 10 parts of present compounds (1) to
(98), 35 parts of white carbon containing 50 parts of polyoxyethylene alkyl ether sulfate ammonium salt, and 55 parts of water is finely grounded by a wet grinding method to obtain a 10% flowable formulation.
Preparation Example 6
Each 0.1 part of present compounds (1) to (98) is dissolved in 5 parts of xylene and 5 parts of
trichloroethane, and the solution is mixed with 89.9 parts of a deodorized kerosene to obtain a 0.1% oil.
Preparation Example 7
Each 10 mg of present compounds (1) to (98) is
dissolved in 0.5 ml of acetone. The solution is mixed uniformly with 5 g of a solid feed powder for animals
(solid feed powder for rearing and breeding CE-2,
manufactured by CLEA Japan, Inc.), and then dried by evaporation of acetone to obtain poison feed.
Then, the following Test Examples will show that the present invention is useful for controlling pests.
Test Example 1-a
Each 10 parts of the present compounds (1) to (6), (8) to (11), (16) to (25), (27), (29) to (34), (37) to (53), (56), (58), (59), (61) to (73), (75), (76), (78), (80),
(87), (89) to (92), (95), (96), (97) and (98); 35 parts of white carbon containing 50 parts of polyoxyethylene alkyl ether sulfate ammonium salt; and 55 parts of water were mixed, and finely grounded by a wet grinding method to obtain a 10% flowable formulation. The obtained flowable formulation was diluted with water so that the active ingredient concentration became to 500 ppm to prepare a spray solution for test.
Cabbages were planted in polyethylene cups, and grown until the third true leaf or the fourth true leaf was developed. The spray solution for test prepared above was sprayed at a rate of 20 ml/cup on the cabbages.
After the pesticidal solution sprayed onto the
cabbages was dried, the root part was removed and put the 'cabbage into 100 ml volume polyethylene cup together with 5 second-instar larvae of Plutella xylostella, and stored at 25°C. After 5 days, the number of dead Plutella xylostella was counted, and the dead pest rate was calculated by the following equation:
Dead pest rate(%) = ( the number of dead pests / the number of tested pests) * 100
As a result, in the treated-area with each of the test spray solutions of present compounds (1) to (6), (8) to (11), (16) to (25), (27), (29) to (34), (37) to (53), (56), (58), (59), (61) to (73), (75), (76), (78), (80), (87), (89) -to (92), (95), (96), (97) and (98), a controlling value of 100% was exhibited.
Test Example 1-b
Each 30 mg of present compounds (13), (14), (15), (35), (36), (54), (55), (74), (81), (82) and (83) was dissolved in 0.1 ml of a mixture of xylene and N,N-dimethyl formamide (mixing volume ratio; xylene : N, N-dimethylformamide = 1:1), 0.1 ml of a mixture of xylene and Solpol 3005X
(manufactured by Toho Chemical Industry Co., Ltd.) (mixing volume ratio; xylene : Solpol 3005X = 1:9) was further added, and the mixture was diluted with ion-exchanged water so that the active ingredient concentration became to a predetermined concentration to prepare a pesticidal
solution for test of the test compound. To cabbage (Brassicae oleracea) in the fourth leaf period was sprayed 20 ml of the pesticidal solution. After' the pesticical solution was dried, and put into a polyethylene cup having a volume of 400 ml together with 10 third-instar larvae of Plutella xylostella, and stored at 250C. After 5 days, the number of dead pests was countered, and the dead pest rate was calculated by the following equation:
Dead pest rate (%) = (the number of dead pests / the number of tested pests) x 100
As a result, the present compounds (13)**, (14)**, (15)**, (35)**, (36), (54), (55)*, (74), (81), (82) and (83) ^exhibited a dead pest rate of 80% or more,
resepctively .
* : test concentration 12.5 ppm
** : test concentration 50 ppm
- Test concentrations 'of the others were 200 ppm.
Test Example 2
Each 2.5 mg of the present compounds (1) to (4), (8), (10), (11), (13), (14), (15), (17), (21), (22), (27), (29) to (33), (35), (38), (41), (42), (43), (44), (45), (46.), (48), (49) and (72) was dissolved in 0.25 ml of a mixture of Solgen TW-20 (manufactured by Dai-ichi Kogyo Seiyaku Co., Ltd.) and acetone (mixing volume ratio; Solgen TW- 20: acetone = 1:19). This mixture was diluted with ion- exchanged water so that the active ingredient concentration became to a predetermined concentration to prepare a pesticidal solution for test of the test' compound. The root part of cabbages in the fourth true leaf stage were washed with tap water to remove soils, and then immersed the root in the pesticidal solution for test. After 5 days from immersion of the root part, the root part was removed, and the leaves and stems were put in a cup (volume; 180 mL) In the cup 10 second-instar larvae of Plutela xylostella were released, and the cup was stored at 24°C. After 5 days, the number of dead pests was counted, and the dead pest rate was calculated by the following equation:
NDead pest rate (%) = (the number of dead pests / the number of tested pests) x 100
As a result, present compounds (1) to (4), (8), (10), (11), (13)**, (14)**, (15)**, (17)*, (21), (22), (27)**, (29) to (33), (35), (38), (-41), (42)**, (43)**, (44),
(45)**, (46), (48), (49)** and (72) exhibited a dead pest rate of 100%, respectively.
* : test concentration of 1 ppm
** : test concentration of 5 ppm
The test concentrations of the other present compounds were 25 ppm.
Test Example 3
Each 10 parts of the present compounds (1) to (15), (17) to (28), (30) to (32), (34), (35), (37) to (53), (56) to (68), (70), (71), (73), (74), (76), (80) to (84), (85), (87) to (92) and (95), 35 parts of white carbon containing 50 parts of polyoxyethylene alkyl ether sulfate ammonium salt and 55 parts of water were mixed, and finely ground by a wet grinding method to obtain a formulation. The
obtained formulation was diluted with water so that the active ingredient concentration became to 500 ppm to
prepare a pesticidal solution for test. On the bottom of a polyethylene cup having a diameter of 5.5 cm, a filter paper having a diameter of 5.5 cm was placed, on which
Insecta LF (Nippon Agriculture Industries, Co., Ltd.) sliced in a thickness of 6 mm and further cut half was laid, and to which 2 mL of the above-described pesticidal
solution for test was added. After air-dried, 5 fourth- instar larvae of Spondoptela litura were released in the cup, and the cup was capped, then the cup was stored at 25°C. After 6 days, the number of dead pests was counted, and the dead pest rate was calculated by the following equation:
Dead pest rate (%) = (the number of dead pests / the number of tested pests) x 100
As a result, the present compounds (1) to (15), (17) to (28), (30) to (32), (34), (35), (37) to (53), (56) to (68), (70), (71), (73), (74), (76), (80) to (85), (87) to (92) and (95) exhibited a dead pest rate of 80% or more, resepctively .
Test Example 4
Each 10 parts of the present compounds (1), (2), (3), (4), (1O)1, (14), (15), (17), (18), (19), (20), (21), (22), (27)., (29), (30), (31), (32), (37), (39), '(40), (41) to
(50), (51), (53), (61), (62), (69), (70), (71), (76), (80), (81), (89), (90) and (92); 35 parts of white carbon
containing 50 parts of polyoxyethylene alkyl ether sulfate ammonium salt; and 55 parts of water were mixed, and finely ground by a wet grinding method to obtain a formulation.
The obtained formulation was diluted with water so that the active ingredient concentration became to a predetermined concentration to prepare a spray solution for test.
Cucumbers were planted in polyethylene cups, and were grown until the first true leaf was developed. The spray
solution for test prepared above was sprayed at the rate of 20 ml/cup on the cucumber. After the pesticidal solution sprayed onto the cucumber was dried, the first true leaf was cut off and then placed on a filter paper (diameter: 70 mm) containing water in a polyethylene cup (diameter: 110 mm) . On the cucumber leaf, 30 nymphs of Frankliniella occidentalis were released, and the polyethylene cup was capped. Seven days after spraying, the number of pests surviving on the cucumber leaf was counted, and a control value was calculated by the following equation: Control value (%) = {l-(Cb * Tai)/(Cai * Tb) } x 100 wherein, each symbol has following meaning:
Cb: the number of pests before treatment in a non- treated area
Cai: the number of pests at the time of observation in a non-treated" area
Tb: the number of pests before treatment in a treated- area
Tai: the number of pests at the time of observation in a treated-area .
^1As a result, in the treated-area with each of the test spray solutions of present compounds (1), (2), (3)*, (4)*, (10), (14), (15), (17)*, (18)*, (19)*, (20)*, (21), (22), (27), (29), (30), (31), (32), (37)*, (39)*, (40)*, (41) to
(50), (51)*, (53), (61), (62), (69), (70), (71), (76), (80), (81), (89), (90) and (92), a controlling value of 100% was exhibited.
*: test concentration 12.5 ppm
The test concentrations of the other present compounds were 50 ppm.
Test Example 5
Resent compound (28)
Figure imgf000326_0001
Comparative compound (compound described in Journal of Agricultural and Food Chemistry (1973) Vol.21 (No. 3), 348- 354)
Figure imgf000326_0002
Each 40 mg of present compound (28) and the
comparative compound was dissolved in 0.1 ml of a mixture of xylene and N, N-dimethylformamide (mixing volume ratio; xylene : N, N-dimethylformamide = 1:1), and 0.1 ml of a mixture of xylene and Solpol 3005X (registered trademark, manufactured by Toho Chemical Industry Co., Ltd.) (mixing volume ratio; xylene : Solpol 3005X = 1:9) was further added thereto. Each of these mixtures was diluted with ion- exchanged water to 12.5 ppm to prepare a pesticidal
solution for test of the test compound. To cabbage
(Brassicae oleracea) in the fifth leaf stage was sprayed the pesticidal solution at a rate of 20 ml/cup. After the pesticical solution was dried, the cabbage was put into a polyethylene cup having a volume of 400 ml together with 10 fourth-instar larvae of Spodoptera litura, and stored at 250C. After 5 days, the number of dead pests was countered, and the dead pest rate was calculated by the following equation:
Dead pest rate (%) = (the number of dead pests / the number of tested pests) x 100
As a result, present compound (28) exhibited a dead pest rate of 100%. On the other hand, the comparative compound had a dead pest rate of 0%.
Test Example 6
Present compound (28)
Figure imgf000327_0001
Comparative compound (compound described in Journal of Agricultural and Food Chemistry (1973) Vol.21 (No. 3), 348- 354)
Figure imgf000327_0002
Each 5 mg of present compound (28) and the comparative compound was dissolved in 0.5 ml of a mixed solution of Sorgen TW-20 (manufactured by Daiichi Industries
Pharmaceuticals, Co., Ltd.) and acetone (mixing volume ratio; Sorgen TW-20 : acetone = 1:19), and diluted with ion- exchanged water to 3 ml to prepare a pesticidal solution for test of the test compound. The pesticidal solution was irrigated on the surface of root soil of cabbage plantlet which had been grown up to the 2.5th lea'f period in a vegetable cell plantlet growing tray. After 5 days from treatment, the root was removed, the stem leaf part was placed into a polyethylene cup (volume 180 ml) together with 10 second-instar larvae of Spodoptera litura, and stored at 240C. After 5 days, the number of dead pests was countered, and the dead pest rate was calculated by the following equation:
Dead pest rate (%) = (the number of dead pests / the number of tested pests) x 100
"■As a result, present compound (28) exhibited a dead pest rate of 100%. On the other hand, the comparative compound had a dead pest rate of 0%.
Test Example 7
Present compound (7)
Figure imgf000328_0001
Present compound (26)
Figure imgf000328_0002
Comparative compound (compound described in US 3933908
Figure imgf000329_0001
Each 2.5 mg of present compounds (7) and (26) and the comparative compound was dissolved in 0.25 ml of a mixed solution of Sόrgen TW-20 (manufactured by Daiichi
Industries Pharmaceuticals, Co., Ltd.) and acetone (mixing volumetric ratio; Sorgen TW-20: acetone = 1:19), and diluted with ion-exchanged water to a predetermined
concentration (5 ppm) to prepare a pesticidal solution for test of the test compound. The root part of cabbages in the fpurth true leaf stage were washed with tap water to remove soils, and then immersed the root in the pesticidal solution for test. After 5 days from immersion of the root part, the root part was removed, and the leaves and stems were put into a cup (volume; 180 mL) . In the cup 10 second-instar larvae of Spodoptera litura were released, and the cup was stored at 24°C. After 5 days, the number of dead pests was counted, and the dead pest rate was calculated by the following equation:
Dead pest rate (%) = (the number of dead pests / the number of tested pests) x 100
As a result, present compounds (7) and (26) exhibited a dead pest rate of 100%. On the other hand, the
comparative compound had a dead pest rate of 0%. Test Example 8
Present compound (I]
Figure imgf000330_0001
Present compound (8;
Figure imgf000330_0002
Present compound ( 17 )
Figure imgf000330_0003
Present compound (29)
Figure imgf000330_0004
Present compound ( 37 )
Figure imgf000330_0005
Comparative compound A (compound described in JP 57-126460 A)
Figure imgf000331_0001
Comparative compound B (compound described in US 2005- 0159599 Al)
Figure imgf000331_0002
Comparative compound C (compound described in EP277748;
Figure imgf000331_0003
Each 2.5 mg of present compounds (1), (8), (17), (29) and (37), and comparative compounds A, B and C was
dissolved in 0.25 ml of a mixture of Sorgen TW-20
(manufactured by Daiichi 'Industries Pharmaceuticals, Co., Ltd. ) and acetone (mixing volume ratio; Sorgen TW- 20: acetone = 1:19), and diluted with ion-exchanged water to a predetermined concentration (25 ppm) to prepare a
pesticidal solution for test of the test compound. The root part of cabbages in the fourth leaf period were washed with tap water to remove soils, and then immersed the root in the pesticidal solution for test. After 5 days from immersion of the root part, the root part was removed, and the leaves and stems were put into a cup (volume; 180 mL) . In the cup 10 second-instar larvae of Plutela xylostella were released, and the cup was stored atv 240C. After 5 days, the number of dead pests was counted, and the dead pest rate was calculated by the following equation:
Dead pest rate (%) = (the number of dead pests / the number of tested pests) x 100
As a result, present compounds (1), (8), (17), (29) and (37) exhibited a dead pest rate of 100%, respectively.
On the other hand, the comparative compound A had a dead pest rate of 5%, and compounds B and C had a dead pest rate of 0%.
Test NExampIe 9
A filter paper having a diameter of 33 mm (No. 1026 manufactured by Toyo Filter Paper, Co., Ltd.) was treated with acetone solution (1 mL) of 10 mg / mL of present compounds (1) or (29) using a pipette, and dried at room temperature. Hereinafter, the resulting filter paper is referred to as a filter paper bait.
Four % agarose was poured into a plastic petri dish having a diameter of 9 cm to make the thickness about 5 mm, and solidified by allowing to stand at room temperature.
One circular hole having a diameter of 35 mm (hereinafter, referred to as a well) was made in the solidified agarose.
One filter paper bait was put into the well. Then, after 20 ergates of Coptotermes formosanus were released in the above petri dish, the petri dish was capped, and sealed with a parafilm. After storing in a dark place for 6 weeks, the petri dish was opened. The control rate was calculated by observing the life and death of Coptotermes formosanus in the petri dish. As a result, present compounds (1) and (29) exhibited a control rate of 100%.
Industrial Applicability
The benzoylurea compound of the present invention has an excellent controlling efficacy against pests

Claims

1. A benzoylurea compound represented by the formula (I) :
Figure imgf000334_0001
wherein
X and Y each represent independently an oxygen atom or a sulfur atom,
R1 represents a hydrogen atom,
a formyl group,
a cyano group,
a lower alkylsulfonyl group optionally substituted with one or more substituents,
an arylsulfonyl group optionally substituted with one or more substituents,
a lower alkylcarbonylthio group optionally substituted with one or more substituents,
a lower alkoxycarbonylthio group optionally substituted with one or more substituents,
an aryloxycarbonylthio group optionally substituted with one or more substitutents,
a mono or di (lower alkyl) aminosulfonyl group optionally substituted with one or more substituents,
a mono or diarylaminosulfonyl group optionally substituted with one or more substitutents,
a lower alkyl group optionally substituted with one or more substituents,
a lower alkenyl group optionally substituted with one or more substituents,
a lower alkynyl group optionally substituted with one or more substituents,
a lower cycloalkyl group optionally substituted with one or more substituents,
an aryl lower alkyl group optionally substituted with one or more substituents,
an aryl group optionally substituted with one or more substituents,
a lower alkoxy lower alkyl group optionally substituted with one or more substituents,
an aryloxy lower alkyl group optionally substituted with one or more substituents,
a lower alkylthio lower alkyl group optionally substituted with one or more substituents,
a lower alkylsulfinyl lower alkyl group optionally
substituted with one ore more substituents,
a lower alkylsulfonyl lower alkyl group optionally
substituted with one or more substituents,
a mono or di (lower alkyl) amino lower alkyl group optionally substituted with one or more substituents, a lower alkanoyl group optionally substituted with one or more substituents,
a lower alkoxycarbonyl group optionally substituted with one or more substituents,
an aryloxycarbonyl group optionally substituted with one or more substituents,
an aryl lower alkoxycarbonyl group optionally substituted with one or more substituents,
a carbamoyl group optionally substituted with one or more substituents,
a thiocarbamoyl group optionally substituted with one or more "^substituents,
a lower alkoxyoxalyl group optionally substituted with one or more substituents,
an aryl lower alkoxyoxalyl group optionally substituted with- one or more substituents,
an aryloxyoxalyl group optionally substituted with one or more substituents,
an aminooxalyl group optionally substituted with one or more substituents,
a lower alkoxy group optionally substituted with one or more substituents,
an aryloxy group optionally substituted with one or more substituents,
an aryl lower alkoxy group optionally substituted with one or more substituents,
an amino group optionally substituted with one or more substituents, or
a heterocyclic group optionally substituted with one or more substituents,
R2 represents a lower alkylene group optionally substituted with one or more halogen atoms,
A represents:
(1) a group represented by OR3
(wherein R3 represents a C1-C3 alkyl group optionally substituted with one or more substituents,
a lower alkenyl group optionally substituted with one or more substituents,
a lower alkynyl group optionally substituted with one or more substituents,
a lower alkanoyl group optionally substituted with one or more substituents,
an aryl group optionally substituted with one or more substituents, or
an aryl lower alkyl group optionally substituted with one or more substituents),
(2) a group represented by S(O)nR4
(wherein R4 represents a C1-C3 alkyl group optionally substituted with one or more substituents,
a lower alkenyl group optionally substituted with one or more substituents,
a lower alkynyl group optionally substituted with one or more substituents,
an aryl group optionally substituted with one or more substituents, or
an aryl lower 'alkyl group optionally substituted with one or more substituents, and
n represents an integer of 0, 1 or 2), or
(3) a group represented by NR5R6
(wherein R5 and R6 each represent independently
a C1-C3 alkyl group optionally substituted with one or more substituents,
a lower alkenyl group optionally substituted with one or more substituents,
a lower alkynyl group optionally substituted with one or more substituents,
an aryl group optionally substituted with one or more substituents,
an aryl lower alkyl group optionally substituted with one or more substituents,
or R5 and R6 may be taken together at the ends thereof to form together with the nitrogen atom a 3- to 7-membered nitrogen-containing heterocyclic ring optionally having another nitrogen atom, an oxygen atom or a sulfur atom as a ring constituting atom) , R7 represents a halogen atom,
a nitro group,
a cyano group,
an aryl lower alkoxy group optionally substituted with one or more halogen atoms,
a lower alkanδyl group optionally substituted with one or more halogen atoms,
a lower alkoxycarbonyl group optionally substituted with one or more halogen atoms,
an aryl group optionally substituted with one or more halogen atoms,
an aryl lower alkoxycarbonyl group optionally substituted with one or more halogen atoms,
an arylcarbamoyl group optionally substituted with one or more halogen atoms,
a carbamoyl group optionally substituted with one or more lower alkyl groups,
a thiocarbamoyl group optionally substituted with one or more lower alkyl groups,
an amino group optionally substituted with one or more lower alkyl groups,
a lower alkyl group optionally substituted with one or more halogen atoms,
a lower alkoxy group optionally substituted with one or more halogen atoms, a lower alkoxy lower alkoxy group optionally substituted with one or more halogen atoms,
a lower alkenyloxy group optionally substituted with one or more halogen atoms,
a lower alkynyloxy group optionally substituted with one or more halogen atoms,
a lower alkanoylamino group optionally substituted with one or more halogen atoms,
a lower alkylthio group optionally substituted with one or more halogen atoms,
a lower alkenylthio group optionally substituted with one or more halogen atoms,
a lower alkynylthio group optionally substituted with one or more halogen atoms,
a lower alkylsulfinyl group optionally substituted with one or more halogen atoms,
a lower alkenylsulfinyl group optionally substituted with one or more halogen atoms,
a lower alkynylsulfinyl group optionally substituted with one or more halogen atoms,
a lower alkylsulfonyl group optionally substituted with one or more halogen atoms,
a lower alkenylsulfonyl group optionally substituted with one or more halogen atoms,
a lower alkynylsulfonyl group optionally substituted with one or more halogen atoms,
a lower alkoxy lower alkylthio group optionally substituted with one or more halogen atoms, or
a group represented by -G-E
(wherein G represents an oxygen atom, a sulfur atom, SO, or SO2, and
E represents an aryl group or a heterocyclic group and said aryl group or said heterocyclic group may be
substituted with one or more substituents selected from the group consisting of (1) a halogen atom, (2) a lower alkyl group optionally substituted with one or more halogen atoms, (3) sa lower alkoxy group optionally substituted with one or more halogen atoms, (4) a lower alkylthio group optionally substituted with one or more halogen atoms, (5) a lower alkylsulfinyl group optionally substituted with one or more halogen atoms, (6) a lower alkylsulfonyl group optionally substituted with one or more halogen atoms, (7) a cyano group, and (8) a nitro group), and
Q represents an aryl group optionally substituted with one or more substituents, or a heterocyclic group
optionally substituted with one or more substituents, m represents an integer of 1 to 5 (provided that when m is an integer of 2 to 5, R7 ' s may be the same or different), or a salt thereof.
2. The benzoylurea compound according to claim 1, wherein R7 is a halogen atom,
a lower alkoxycarbonyl group optionally 'substituted with one or more halogen atoms,
a lower alkyl group optionally substituted with one or more halogen atoms,
a lower alkoxy group optionally substituted with one or more halogen atoms,
a lower alkoxy lower alkoxy group optionally substituted with one or more halogen atoms,
a lower alkoxy lower alkylthio group optionally substituted with one or more halogen atoms,
a lower alkenyloxy group optionally substituted with one or more halogen atoms,
a lower alkynyloxy group optionally substituted with one or more halogen atoms,
a lower alkylthio group optionally substituted with one or more halogen atoms,
a lower alkenylthio group optionally substituted with one or more halogen atoms,
a lower alkynylthio group optionally substituted with one or more halogen atoms,
a lower alkylsulfinyl group optionally substituted with one or more halogen atoms,
a lower alkenylsulfinyl group optionally substituted with one or more halogen atoms, a lower alkynylsulfinyl group optionally substituted with one or more halogen atoms,
a lower alkylsulfonyl group optionally substituted with one or more halogen atoms,
a lower alkenylsulfonyl group optionally substituted with one or more halogen atoms,
a lower alkynylsulfonyl group optionally substituted with one or more halogen atoms, or
a group represented by -G-E
(wherein G is an oxygen atom, a sulfur atom, SO, or SO2, and
"i E is an aryl group or a heterocyclic group and said aryl group or said heterocyclic group may be substituted with one or more substituents, selected from the group consisting of (1) a halogen atom, (2) a lower alkyl group optionally substituted with one or more halogen atoms, (3) a lower alkoxy group optionally substituted with one or more halogen atoms, (4) a lower alkylthio group optionally substituted with one or more halogen atoms, (5) a lower alkylsulfinyl group optionally substituted with one or more halogen atoms, (6) a lower alkylsulfonyl group optionally substituted with one or more halogen atoms, (7) a cyano group, and (8) a nitro group) .
3. The benzoylurea compound according to claiml, wherein R1 is a hydrogen atom, a lower alkyl group optionally substituted with one or more substituents,
a lower alkenyl group optionally substituted with one or more substituents,
a lower alkynyl group optionally substituted with one or more substitue~nts,
an aryl lower alkyl group optionally substituted with one or more substituents,
a lower alkoxy lower alkyl group optionally substituted with one or more substituents,
an aryloxy lower alkyl group optionally substituted with one or more substituents,
a lower alkanoyl group optionally substituted with one or more substituents,
a lower alkylthio lower alkyl group optionally substituted with one or more substituents,
a lower alkylsulfinyl lower alkyl group optionally
substituted with one or more substituents,
a lower alkylsulfonyl lower alkyl group optionally
substituted with one or more substituents, or
a mono or di (lower alkyl) amino lower alkyl group optionally substituted with one or more substituents.
4. The benzoylurea compound according to any one of claims 1 to 3, wherein R2 is a C1-C4 alkylene group
optionally substituted with one or more halogen atoms.
5. The benzoylurea compound according to claim 1, wherein X and Y are an oxygen atom, and
A is a group represented by OR3
(wherein R3 is a C1-C3 alkyl group optionally substituted with one or more substituents,
a lower alkenyl group optionally substituted with one or more substituents,
a lower alkynyl group optionally substituted with one or more substituents,
a lower alkanoyl group optionally substituted with one or more substituents, or
an afyl lower alkyl group optionally substituted with one or more substituents) .
6. The benzoylurea compound according to any one of claims 1 to 5, wherein A is a group represented by OR3
(wherein R3 is a C1-C3 alkyl group optionally substituted with one or more substituents,
a lower alkanoyl group optionally substituted with one or more substituents, or
an aryl lower alkyl group optionally substituted with one or more substituents).
7. The benzoylurea compound according to claim 1, wherein X and Y are an oxygen atom, and
A is a group represented by S(O)nR4
(wherein R4 is a C1-C3 alkyl group optionally substituted with one or more substituents,
a lower alkenyl group optionally substituted with one or more substituents,
a lower alkynyl group optionally substituted with one or more substituents, or
an aryl group optionally substituted with one or more substituents, and
n is an integer of 0 to 2) .
8. The benzoylurea compound according to claim 1, wherein X and Y are an oxygen atom, and
A is a group represented by NR5R6
(wherein R5 and R6 each are independently
a C1-C3 alkyl group optionally substituted with one or more substituents,
a lower alkenyl group optionally substituted with one or more substituents,
a lower alkynyl group optionally substituted with one or more substituents,
an aryl group optionally substituted with one or more substituents, or
R5 and R6 are taken together at the ends thereof to form together with the nitrogen atom a 3- to 7-membered
nitrogen-containing heterocycle optionally having another nitrogen atom, an oxygen atom or a sulfur atom as a ring constituting atom) .
9. The benzoylurea compound according to any one of claims 1 to 8, wherein Q is a phenyl group optionally substituted with one or more substituents selected from the group consisting of (1) a halogen atom, (2) a lower alkyl group optionally substituted with one or more halogen atoms, and (3) a lower alkoxy group optionally substituted with one or more halogen atoms, or
an aromatic monocyclic heterocyclic group substituted with one or more substituents selected from the group consisting of (1) a halogen atom, (2) a lower alkyl group optionally substituted with one or more halogen atoms, and (3) a lower alkoxy group optionally substituted with one or more
halogen atoms.
10. The benzoylurea compound according to claim 1, wherein Q is a phenyl group optionally substituted with one or more halogen atoms, or an aromatic monocyclic
heterocyclic group optionally substituted with one or more halogen atoms.
11. The benzoylurea compound according to claim 1, wherein X and Y are an oxygen atom, and
R1 is a hydrogen atom,
a lower alkyl group optionally substituted with one or more substituents,
a lower alkenyl group optionally substituted with one or more substituents, a lower alkynyl group optionally substituted with one or more substituents,
an aryl lower alkyl group optionally substituted with one or more substituents,
a lower alkoxy lower alkyl group optionally substituted with one or mo"re substituents,
an aryloxy lower alkyl group optionally substituted with one or more substituents,
a lower alkylthio lower alkyl group optionally substituted with one or more substituents,
a lower alkylsulfinyl lower alkyl group optionally
substituted with one or more substituents,
a lower alkylsulfonyl lower alkyl group optionally
substituted with one or more substituents,
a mono or di (lower alkyl) amino lower alkyl group optionally substituted with one or more substituents, or
a lower alkanoyl group optionally substituted with one or more substituents,
R2 is a methylene group, an ethylene group, or a trimethylene group,
A represents:
(1) a group represented by OR3
(wherein R3 is a C1-C3 alkyl group optionally substituted with one or more substituents,
a lower alkanoyl group optionally substituted with one or more substituents, or
an aryl lower alkyl group optionally substituted with one or more substituents),
(2) a group represented by S(O)nR4
(wherein R4 is a C1-C3 alkyl group optionally substituted with one or more substituents, and
n is an integer of 0 to 2), or
(3) a group represented by NR5R6
(wherein R5 and R6 each are independently a C1-C3 alkyl group optionally substituted with one or more substituents, or
*ΪR5 and R6 are taken together at the ends thereof to form together with the nitrogen atom a 3- to 7-membered nitrogen-containing heterocycle optionally having another nitrogen atom, an oxygen atom or a sulfur atom as a ring constituting atom) ,
R7 is a halogen atom,
a lower alkoxycarbonyl group optionally substituted with one or more halogen atoms,
a lower alkyl group optionally substituted with one or more halogen atoms,
a lower alkoxy group optionally substituted with one or more halogen atoms,
a lower alkoxy lower alkoxy group optionally substituted with one or more halogen atoms, a lower alkylthio group optionally substituted with one or more halogen atoms,
a lower alkenylthio group optionally substituted with one or more halogen atoms,
a lower alkynylthio group optionally substituted with one or more halogen atoms,
a lower alkylsulfinyl group optionally substituted with one or more halogen atoms,
a lower alkenylsulfinyl group optionally substituted with one or more halogen atoms,
a lower alkylsulfonyl group optionally substituted with one or more halogen atoms,
a lower alkenylsulfonyl optionally substituted with one or more halogen atoms,
a lower alkoxy lower alkylthio group optionally substituted with one or more halogen atoms, or
a group represented by -G-E
(wherein G is an oxygen atom, or a sulfur atom, and
E is an aryl group or a heterocyclic group optionally substituted with one or more substituents selected from the group consisting of (1) a halogen atom, and (2) a lower alkyl group optionally substituted with one or more halogen atoms) ,
Q is a 2, β-difluorophenyl group, a 2-chloro-6- fluorophenyl group, a 2, 6-dichlorophenyl group, a 3- chloropyridin-2-yl group, or a 3, 5-dichloropyridin-4-yl group, and
m is an integer of 1 to 4 (provided that when m is an integer of 2 to 4, R7 ' s may be the same or different) .
12. The benzoylurea compound according to claim 1, wherein X and Υ are an oxygen atom,
R1 is a hydrogen atom,
a lower alkyl group optionally substituted .with one or more substituents,
a lower alkenyl group optionally substituted with one or more substituents,
a lower alkynyl group optionally substituted with one or more substituents,
a lower alkoxy lower alkyl group optionally substituted with one or more substituents,
an aryloxy lower alkyl group optionally substituted with one or more substituents,
a lower alkylthio lower alkyl group optionally substituted with one or more substituents,
a lower alkylsulfonyl lower alkyl group optionally
substituted with one or more substituents, or
a lower alkanoyl group optionally substituted with one or more substituents,
R2 is a methylene group, an ethylene group, or a trimethylene group, A represents:
(1) a group represented by OR3
(wherein R3 is a C1-C3 alkyl group optionally substituted with one or more substituents,
a lower alkanoyl group optionally substituted with one or more substituents, or
an aryl lower alkyl group optionally substituted with one or more substituents),
(2) a group represented by S(O)nR4
(wherein R4 is a C1-C3 alkyl group optionally substituted with one or more substituents, and
^n is an integer of 0 to 2), or
(3) a group represented by NR5R6
(wherein R5 and R6 each are independently a C1-C3 alkyl group optionally substituted with one or more substituents, or
R5 and R6 are taken together at the ends thereof to form together with the nitrogen atom a 3- to 7-membered nitrogen-containing heterocycle optionally having another nitrogen atom, an oxygen atom or a sulfur atom as a ring constituting atom) ,
R7 is a halogen atom,
a lower alkoxycarbonyl group optionally substituted with one or more halogen atoms,
a lower alkyl group optionally substituted with one or more halogen atoms,
a lower alkoxy group optionally substituted with one or more halogen atoms,
a lower alkoxy lower alkoxy group optionally substituted with one or more halogen atoms,
a lower alkylthio group optionally substituted with one or more halogen atoms,
a lower alkenylthio group optionally substituted with one or more halogen atoms,
a lower alkynylthio group optionally substituted with one or more halogen atoms,
a lower alkylsulfinyl group optionally substituted with one or more halogen atoms,
a lower alkenylsulfinyl group optionally substituted with one or more halogen atoms,
a lower alkylsulfonyl group optionally substituted with one or more halogen atoms,
a lower alkoxy lower alkylthio group optionally substituted with one or more halogen atoms, or
a group represented by -G-E
(G is an oxygen atom, or a sulfur atom, and
E is an aryl group or a heterocyclic group and said aryl group or said heterocyclic group may be substituted with one or more substituents selected from the group consisting of (1) a halogen atom, and (2) a lower alkyl group optionally substituted with one or more halogen atoms) ,
Q is a 2, 6-difluorophenyl group, a 2-chloro-6- fluorophenyl group, a 2 , 6-dichlorophenyl group, a 3- chloropyridin-2-yl group, or a 3, 5-dichloropyridin-4-yl group, and
m is an integer of 1 to 4 (provided that when m is an integer of 2 to 4, R7s may be the same or different) .
13. A pest controlling agent comprising the
benzoylurea compound according to claim 1 or a salt thereof as an active ingredient.
M4. Use of the benzoylurea compound according to claim 1 or a salt thereof for controlling pests.
15. A method for controlling pests or plant- parasiting pests, which comprises applying an effective amount of the benzoylurea compound according to claim 1 or a salt thereof to pests or habitats of pests.
PCT/JP2006/323048 2005-12-07 2006-11-13 Benzoylurea compound and use thereof WO2007066496A1 (en)

Applications Claiming Priority (6)

Application Number Priority Date Filing Date Title
JP2005-353179 2005-12-07
JP2005353179 2005-12-07
JP2006-097943 2006-03-31
JP2006097943 2006-03-31
JP2006209598 2006-08-01
JP2006-209598 2006-08-01

Publications (1)

Publication Number Publication Date
WO2007066496A1 true WO2007066496A1 (en) 2007-06-14

Family

ID=37715623

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP2006/323048 WO2007066496A1 (en) 2005-12-07 2006-11-13 Benzoylurea compound and use thereof

Country Status (3)

Country Link
AR (1) AR057992A1 (en)
TW (1) TW200804250A (en)
WO (1) WO2007066496A1 (en)

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009008287A1 (en) * 2007-07-06 2009-01-15 Sumitomo Chemical Company, Limited 4-(trichloromethylthio)aniline, method for producing the same, and method for producing 4-(trifluoromethylthio)aniline
CN104430546A (en) * 2014-12-09 2015-03-25 陈干忠 High-yield disease-resistant and mothproof composite preparation for rubber trees as well as preparation method and application thereof
CN109890789A (en) * 2016-11-03 2019-06-14 默克专利股份有限公司 Fluorine-containing surfactant
CN110526863A (en) * 2019-08-29 2019-12-03 贵州大学 The acylthioureas and acyl group carbamide derivative of a kind of trifluoromethyl pyridine and its application

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE2916140A1 (en) * 1978-04-21 1979-10-31 Egyt Gyogyszervegyeszeti Gyar 1,3-DIPHENYL-2-IMINOIMIDAZOLIDINE AND 1,3-DIPHENYL-2-IMINOHEXAHYDROPYRIMIDINE, METHOD FOR THEIR MANUFACTURING AND DRUGS CONTAINING SUCH
WO1986003941A1 (en) * 1984-12-28 1986-07-17 Union Carbide Corporation Use of acyl urea compounds for controlling endoparasites and ectoparasites of warm-blooded animals
US6376430B1 (en) * 1997-09-30 2002-04-23 Uniroyal Chemical Company, Inc. Enhancement of seed yield of soybeans by a substituted benzoyl urea
WO2002070509A2 (en) * 2001-03-01 2002-09-12 Telik, Inc. Antagonists of mcp-1 function and methods of use thereof

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE2916140A1 (en) * 1978-04-21 1979-10-31 Egyt Gyogyszervegyeszeti Gyar 1,3-DIPHENYL-2-IMINOIMIDAZOLIDINE AND 1,3-DIPHENYL-2-IMINOHEXAHYDROPYRIMIDINE, METHOD FOR THEIR MANUFACTURING AND DRUGS CONTAINING SUCH
WO1986003941A1 (en) * 1984-12-28 1986-07-17 Union Carbide Corporation Use of acyl urea compounds for controlling endoparasites and ectoparasites of warm-blooded animals
US6376430B1 (en) * 1997-09-30 2002-04-23 Uniroyal Chemical Company, Inc. Enhancement of seed yield of soybeans by a substituted benzoyl urea
WO2002070509A2 (en) * 2001-03-01 2002-09-12 Telik, Inc. Antagonists of mcp-1 function and methods of use thereof

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
GREENE, WUTS: "Protecting groups in organic synthesis", 1999, JOHN WILLEY AND SONS, ISBN: 0-471-22057-4, XP002422701 *
WELLINGA K ET AL: "SYNTHESIS AND LABORATORY EVALUATION OF 1-(2,6-DISUBSTITUTED BENZOYL)-3-PHENYLUREAS, A NEW CLASS OF INSECTICIDES. I. 1-(2,6-DICHLOROBENZOYL)-3-PHENYLUREAS", JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY, AMERICAN CHEMICAL SOCIETY. WASHINGTON, US, vol. 21, no. 3, 1973, pages 348 - 354, XP002016453, ISSN: 0021-8561 *

Cited By (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009008287A1 (en) * 2007-07-06 2009-01-15 Sumitomo Chemical Company, Limited 4-(trichloromethylthio)aniline, method for producing the same, and method for producing 4-(trifluoromethylthio)aniline
JP2009013130A (en) * 2007-07-06 2009-01-22 Sumitomo Chemical Co Ltd 4-(trichloromethylthio)anilines, method for producing the same and method for producing 4-(trifluoromethylthio)anilines
US8399707B2 (en) 2007-07-06 2013-03-19 Sumitomo Chemical Company, Limited 4-(trichloromethylthio) anilines, method for production thereof, and method for producing 4-(trifluoromethylthio) anilines
US8466321B2 (en) 2007-07-06 2013-06-18 Sumitomo Chemical Company, Limited 4-(trichloromethylthio) anilines, method for production thereof, and method for producing 4-(trifluoromethylthio) anilines
KR101435703B1 (en) 2007-07-06 2014-09-01 스미또모 가가꾸 가부시끼가이샤 4-(trichloromethylthio)aniline, method for producing the same, and method for producing 4-(trifluoromethylthio)aniline
CN104430546A (en) * 2014-12-09 2015-03-25 陈干忠 High-yield disease-resistant and mothproof composite preparation for rubber trees as well as preparation method and application thereof
CN104430546B (en) * 2014-12-09 2017-04-19 陈干忠 High-yield disease-resistant and mothproof composite preparation for rubber trees as well as preparation method and application thereof
CN109890789A (en) * 2016-11-03 2019-06-14 默克专利股份有限公司 Fluorine-containing surfactant
US11535589B2 (en) 2016-11-03 2022-12-27 Merck Patent Gmbh Fluorinated tensides
CN110526863A (en) * 2019-08-29 2019-12-03 贵州大学 The acylthioureas and acyl group carbamide derivative of a kind of trifluoromethyl pyridine and its application
CN110526863B (en) * 2019-08-29 2022-05-03 贵州大学 Acyl thiourea or acyl urea derivative containing trifluoromethylpyridine and application thereof

Also Published As

Publication number Publication date
AR057992A1 (en) 2008-01-09
TW200804250A (en) 2008-01-16

Similar Documents

Publication Publication Date Title
EP2646433B1 (en) Pyrimidine compound and use for pest control thereof
CA2896453C (en) Fused oxazole compounds and use thereof for pest control
EP1937629A2 (en) Benzoylurea compounds and use thereof
EP1386915A1 (en) Azole compounds, process for preparation of the same and use thereof
US20120041009A1 (en) Pyrimidine compound and its use in pest control
KR20080072029A (en) Iminopropene compound and use thereof
CA2704546A1 (en) Pyridine compound, pesticidal composition and method of controlling pest
EP2332936B1 (en) Pyridine compound and use thereof for pest control
JP4370107B2 (en) Cyclic compound, its production method and pest control agent
WO2007066496A1 (en) Benzoylurea compound and use thereof
JP5239148B2 (en) 3-Iminopropene compound, pest control agent containing it, and its use for pest control
JP2005194250A (en) Triazole compound, method for producing the same and use thereof
WO2010119879A1 (en) Pyrimidine compound and its use for pest control
JP2010168328A (en) N-phenylimine compound and use thereof for pest control
WO2008149962A1 (en) Thioimidate compound and use thereof for controlling pests
JP2008056650A (en) N-aryl-n-substituted urea compound
US20080280988A1 (en) Use of (N&#39;-Methyl) benzoylurea compound
JP2008037854A (en) N&#39;-alkylbenzoylurea compound
US20080274884A1 (en) Novel use of (N&#39;-methyl)benzoylurea compound
JP2003026663A (en) Azole compound, method for producing the same and application of the same
JP2007297376A (en) Method for protecting plant
WO2007116949A1 (en) Plant protection method
JP2007297375A (en) Method for protecting plant

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application
NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 06832925

Country of ref document: EP

Kind code of ref document: A1