WO2008130021A2 - Heterocyclic hydrazide compound and pesticidal use of the same - Google Patents

Heterocyclic hydrazide compound and pesticidal use of the same Download PDF

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Publication number
WO2008130021A2
WO2008130021A2 PCT/JP2008/057560 JP2008057560W WO2008130021A2 WO 2008130021 A2 WO2008130021 A2 WO 2008130021A2 JP 2008057560 W JP2008057560 W JP 2008057560W WO 2008130021 A2 WO2008130021 A2 WO 2008130021A2
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Prior art keywords
optionally substituted
halogen atoms
halogen
atom
group
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PCT/JP2008/057560
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French (fr)
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WO2008130021A3 (en
Inventor
Markus Jachmann
Yoshihiko Nokura
Hiroshi Ikegami
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Sumitomo Chemical Company, Limited
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Application filed by Sumitomo Chemical Company, Limited filed Critical Sumitomo Chemical Company, Limited
Priority to EP08740616A priority Critical patent/EP2144898B1/en
Priority to ES08740616T priority patent/ES2380272T3/en
Priority to CN200880019285A priority patent/CN101679377A/en
Priority to MX2009010824A priority patent/MX2009010824A/en
Priority to CA002681779A priority patent/CA2681779A1/en
Priority to US12/594,452 priority patent/US8247431B2/en
Priority to BRPI0811046-8A2A priority patent/BRPI0811046A2/en
Priority to AT08740616T priority patent/ATE544760T1/en
Priority to AU2008241790A priority patent/AU2008241790A1/en
Publication of WO2008130021A2 publication Critical patent/WO2008130021A2/en
Publication of WO2008130021A3 publication Critical patent/WO2008130021A3/en

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/34—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom
    • A01N43/40—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom six-membered rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings

Definitions

  • the present invention relates to a hydrazide compound and pesticidal use of the same.
  • WO 2002/ 070483 discloses several 5- and 6-membered heteroaromatic diamide compounds activity. Furthermore, in WO 2007/020050 is heterobicylic diamide compounds described and their use of for controlling harmful pests in agriculture.
  • the present invention is intended to provide a compound having excellent efficacy of controlling pests.
  • the present inventors have intensively studied in order to find out a compound having excellent efficacy of controlling pests and, as a result, found out that a hydrazide compound represented by the following formula (1) has excellent controlling efficacy.
  • a hydrazide compound represented by the following formula (1) has excellent controlling efficacy.
  • the present invention has been completed. According to the present invention, there is provided:
  • a hydrazide compound represented by the formula (I) (hereinafter referred to as the present compound) , an N- oxide thereof or suitable salt thereof:
  • a 1 and A 2 independently represent an oxygen atom or a sulfur atom
  • E represents, together with the two contiguous linking carbon atoms, a 5- or 6-membered heteroaromatic ring system or a 8, 9 or 10-membered fused heterobicyclic ring system
  • R 1 represents a hydrogen atom, C1-C6 alkyl optionally substituted with one or more halogen atoms, C2-C6 cyanoalkyl, C1-C6 hydroxyalkyl, C2-C6 alkoxyalkyl optionally substituted with one or more halogen atoms, C2- C6 alkenyl optionally substituted with one or more halogen atoms, C2-C6 alkynyl optionally substituted with one or more halogen atoms, C3-C6 cycloalkyl optionally substituted with one or more halogen atoms, C1-C6 alkylthio optionally substituted with one or more halogen atoms, C1-C6 alkylsulfinyl optionally substituted with one or more halogen atoms, Cl-C ⁇ alkylsulfonyl optionally substituted with one or more halogen atoms, C2-C6 alkylcarbonyl optionally substituted with one or more hal
  • R 2 and R 3 independently represent a hydrogen atom, Cl- C6 alkyl optionally substituted with one or more halogen atoms, C2-C6 cyanoalkyl, C1-C6 hydroxyalkyl, C2-C6 alkoxyalkyl optionally substituted with one or more halogen atoms, C2-C6 alkenyl optionally substituted with one or more halogen atoms, C2-C6 alkynyl optionally substituted with one or more halogen atoms, C3-C6 cycloalkyl optionally substituted with one or more halogen atoms, C1-C6 alkylthio optionally substituted with one or more halogen atoms, Cl- C ⁇ alkylsulfinyl optionally substituted with one or more halogen atoms, C1-C6 alkylsulfonyl optionally substituted with one or more halogen atoms, C2-C6 alkylcarbonyl optionally substituted with one or
  • R 4 represents a halogen atom, cyano, nitro, hydroxyl, carboxyl, C1-C6 alkyl optionally substituted with one or more halogen atoms, Cl-C ⁇ alkoxy optionally substituted with one or more halogen atoms, C2-C6 cyanoalkyl, C2-C6 alkoxyalkyl optionally substituted with one or more halogen atoms, C2-C6 alkenyl optionally substituted with one or more halogen atoms, C2-C6 alkynyl optionally substituted with one or more halogen atoms, C3-C6 cycloalkyl optionally substituted with one or more halogen atoms, C1-C6 alkylthio optionally substituted with one or more halogen atoms, Cl- C ⁇ alkylsulfinyl optionally substituted with one or more halogen atoms, Cl-C ⁇ alkylsulfonyl optionally substituted with one or more
  • n an integer of 0 to 3 (provided that, when n is an integer of 2 or more, R 4' s may be the same or different) ;
  • Q represents Ql , Q2 , Q3 , Q4 , Q5 or Q6 :
  • a 31 , A 32 , A 33 and A 34 represent an oxygen atom, or a sulfur atom; m represents an integer of 0 to 2
  • R 6 represents a hydrogen atom; C2-C6 alkenyl optionally substituted with one or more halogen atoms; C2- C6 alkynyl optionally substituted with one or more halogen atoms; C1-C6 alkyl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) C1-C6 alkoxy optionally substituted with one or more halogen atoms, (3) C1-C6 alkylthio optionally substituted with one or more halogen atoms, (4) C1-C6 alkylsulfinyl optionally substituted with one or more halogen atoms, (5) C1-C6 alkylsulfonyl optionally substituted with one or more halogen atoms, (6) C2-C6 dialkylamino optionally substituted with one or more halogen atoms, and (7) C3-C6 cycloalkyl optionally substituted with one or more hal
  • R 7 and R 8 represent C1-C6 alkyl optionally substituted with one or more halogen atoms; C2-C6 alkoxyalkyl optionally substituted with one or more halogen atoms; C2- C6 alkenyl optionally substituted with one or more halogen atoms; C2-C6 alkynyl optionally substituted with one or more halogen atoms; C3-C6 cycloalkyl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, and (2) C1-C6 alkyl optionally substituted with one or more halogen atoms; phenyl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) C1-C6 alkyl optionally substituted with one or more halogen atoms, (5) C1-C6 alkoxy optionally substituted with one or more halogen atom
  • R 9 and R 10 independently represent a hydrogen atom; Cl- C6 alkyl optionally substituted with one or more halogen atoms; C2-C6 alkoxyalkyl optionally substituted with one or more halogen atoms; C2-C6 alkenyl optionally substituted with one or more halogen atoms; C2-C6 alkynyl optionally substituted with one or more halogen atoms; C3-C6 cycloalkyl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, and (2) C1-C6 alkyl optionally substituted with one or more halogen atoms; phenyl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) C1-C6 alkyl optionally substituted with one or more halogen atoms, (5) C1-C6 alkoxy optionally substituted with one or
  • R 11 represents C1-C6 alkyl optionally substituted with one or more halogen atoms; C3-C6 cycloalkyl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, and (2) C1-C6 alkyl optionally substituted with one or more halogen atoms; or a phenyl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) C1-C6 alkyl optionally substituted with one or more halogen atoms and (5) Cl-C ⁇ alkoxy optionally substituted with one or more halogen atoms; 5- to 6-membered heteroaryl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) C1-C6 alkyl optionally substituted with one or more halogen atoms and
  • R 12 and R 13 independently represent C1-C6 alkyl optionally substituted with one or more halogen atoms; C3- C6 cycloalkyl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, and (2) C1-C6 alkyl optionally substituted with one or more halogen atoms; or phenyl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) C1-C6 alkyl optionally substituted with one or more halogen atoms and (5) C1-C6 alkoxy optionally substituted with one or more halogen atoms;
  • J represents Jl or J2 :
  • X a , Y a , Z a , X b , Y b and Z b independently represent CH or a nitrogen atom;
  • R 19a and R 19b represent a hydrogen atom; C1-C6 alkyl optionally substituted with one or more halogen atoms; C2- C6 cyanoalkyl, C2-C6 alkoxyalkyl optionally substituted with one or more halogen atoms; C2-C6 alkenyl optionally substituted with one or more halogen atoms; C2-C6 alkynyl optionally substituted with one or more halogen atoms; C3- C6 cycloalkyl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, and (2) C1-C6 alkyl optionally substituted with one or more halogen atoms; phenyl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) C1-C6 alkyl optionally substituted with one or more halogen atoms, (5) C1
  • R 20a and R 2Ob represent a halogen atom; cyano; nitro; thiocyanato; C1-C6 alkyl optionally substituted with one or more halogen atoms; C1-C6 alkoxy optionally substituted with one or more halogen atoms; C2-C6 cyanoalkyloxy; C2-C6 alkoxyalkyloxy optionally substituted with one or more halogen atoms; C2-C6 alkenyloxy optionally substituted with one or more halogen atoms; C2-C6 alkynyloxy optionally substituted with one or more halogen atoms; C1-C6 alkylthio optionally substituted with one or more halogen atoms; Cl- C6 alkylsulfinyl optionally substituted with one or more halogen atoms; C1-C6 alkylsulfonyl optionally substituted with one or more halogen atoms; phenyl optionally substituted
  • p represents an integer of 0 to 3 (provided that, when p is an integer of 2 or 3, two or more R 20a' s may be the same or different) ;
  • q represents an integer of 0 to 3 (provided that, when q is an integer of 2 or 3, two or more R 20b' s may be the same or different) .
  • this invention also contains a method of controlling an invertebrate pest applying the present compound, an N-oxide thereof or an agricultural suitable salt thereof by contacting directly to a pest, or to a place where a pest inhabits.
  • a method of controlling an invertebrate pest applying the present compound, an N-oxide thereof or an agricultural suitable salt thereof by contacting directly to a pest, or to a place where a pest inhabits.
  • the present compound, an N-oxide thereof or an agricultural suitable salt thereof as active ingredient in a pesticidal composition.
  • a composition comprising of the present compound, an ⁇ V-oxide thereof or an agricultural suitable salt thereof and at least one additional component selected from the group of surfactants, solid diluents and liquid diluents.
  • This invention also includes a method for controlling an invertebrate pest by using the present compound, an N-oxide thereof or an agricultural suitable salt thereof as active ingredient in a pesticidal composition and a biological active amount of at least one additional compound or agent.
  • the invention also pertains the use of the present compound, an N-oxide thereof or an agricultural suitable salt thereof for manufacturing a pesticidal preparation.
  • the compounds of this invention include every possible sterioisomer in terms of enantiomers and diastereomers that can be formed from different configuration at centers of asymmetry and different double bond configuration according to well-accepted definition of configuration isomers (Eliel, Ernest L., Wilien, Samuel H., Stereochemistry of Organic Compounds, John Wiley & Son,
  • the compounds of the invention can be present as a mixture of the above-mentioned isomers, as a single diastereomer or in an optically enriched form as active ingredients.
  • the compounds of formula I of this invention can be present as an N-oxide thereof or an agricultural suitable salt thereof. All available nitrogen atoms whose lone pairs are not part of an aromatic molecular ⁇ -orbital according to Huckel's rule can be oxidized at their lone pairs to form N-oxides by using commonly known methods.
  • Agricultural suitable salts of the compounds of this invention can be formed by addition of an inorganic or organic acid to the compound like for example hydrochloric, hydrobromic, sulfuric, nitric and phosphoric acid as well as acetic, propionic, butyric, oxalic, malonic, tartaric, lactic, maleic, fumaric, citric, p- toluenesulfonic and salicylic acid.
  • an inorganic or organic acid for example hydrochloric, hydrobromic, sulfuric, nitric and phosphoric acid as well as acetic, propionic, butyric, oxalic, malonic, tartaric, lactic, maleic, fumaric, citric, p- toluenesulfonic and salicylic acid.
  • salts can be formed by addition of an inorganic or organic base like e.g.
  • 'aromatic' and ⁇ heteroaromatic' indicates that the carbocyclic or heterocyclic ring system is fully unsaturated with a planar ring system allowing the ring systems p-orbitals and optionally lone pair orbitals of heteroatoms, which are perpendicular to the ring plane to overlap to form a ⁇ -molecular orbital with (4n+2) ⁇ - electrons according to Htickel's rule (n is 0 or a positive integer) .
  • 'non-aromatic' or ⁇ non- aromatic heterocyclic ring system' refers to a ring system, which is fully or partial saturated or which is fully unsaturated but does not fulfill the requirements of Huckel's rule as mentioned above.
  • the term 'hetero' in 'heteroaromatic' , 'heterobicyclic' and 'non-aromatic heterocyclic ring' denotes a ring system that contains at least one or more atom different from carbon, selected from the group of oxygen, nitrogen and sulfur.
  • the heterocyclic ring system can be attached at any available carbon or nitrogen atom by replacement of hydrogen.
  • Examples of the 5- or 6-membered heteroaromatic ring system substitutede with (R 4 ) n include E-I to E-39 shown below.
  • E-1 E-2 E-3 E-4 E-5 E-X8 ⁇ R4) "-l EX-9 ⁇ R4) » ⁇ E-10 °2 V:5 CS * .
  • Examples of the 8, 9 or 10-membered fused heterobicyclic ring system substituted with (R 4 ) n include E-40 to E-109 shown below. Substitution of said heterobicyclic ring systems with substituents R 4 is possible by substitution of carbon and nitrogen H-atoms on the aromatic ring systems as well as on non-aromatic linking moieties (E-97-101, E-103, E-105, E-107-109) .
  • E-105 E-106 E-107 E-108 E-109 Preferred ring systems include E-2, E-4, E-I, E-12, E-13, E-22, E-40 and E47; most preferred E-2 and E-4.
  • halogen atom examples include a fluorine atom, a chlorine atom, a bromine atom and an iodine atom.
  • C1-C6 alkyl optionally substituted with one or more halogen atoms include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl and hexyl as well as fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, 2, 2, 2-trifluoroethyl, 1,1,2,2- tetrafluoroethyl and pentafluoroethyl .
  • C2-C6 cyanoalkyl examples include cyanomethyl and 2-cyanoethyl .
  • C2-C6 cyanoalkoxy examples include cyanomethoxy and 2-cyanoethoxy .
  • Cl-C ⁇ hydroxyalky examples include hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, 1-hydroxypropyl, 2- hydroxypropyl, 3-hydroxypropyl and 2-hydroxy-isopropyl .
  • C1-C6 alkoxy optionally substituted with one or more halogen atoms include methoxy, trifluoromethoxy, ethoxy, 2, 2, 2-trifluoroethoxy, propyloxy, isopropyloxy, butoxy, isobutyloxy, sec-butoxy, tert-butoxy, pentyloxy and hexyloxy .
  • C2-C6 alkoxyalkyl optionally substituted with one or more halogen atoms examples include methoxymethyl, ethoxymethyl, 2-methoxyethyl, 2-ethoxyethyl and 2- isopropyloxyethyl .
  • C2-C6 alkoxyalkyloxy optionally substituted with one or more halogen atoms examples include 2- (methoxy) ethoxy .
  • C2-C6 alkenyl optionally substituted with one or more halogen atoms examples include 2-propenyl, 3-chloro-2- propenyl, 2-chloro-2-propenyl, 3, 3-dichloro-2-propenyl, 2- butenyl, 3-butenyl, 2-methyl-2-propenyl, 3-methyl-2-butenyl, 2-pentenyl and 2-hexenyl as well as polyenes like 1,3- pentadienyl and 2, 4-hexadienyl and all possible diastereomers .
  • C2-C6 alkenyloxy optionally substituted with one or more halogen atoms examples include 2-propenyloxy, 3,3- dichloro-2-propenoxy and 2-methyl-2-propenyloxy .
  • C2-C6 alkynyl optionally substituted with one or more halogen atoms examples include 2-propynyl, 3-chloro-2- propynyl, 3-bromo-2-propynyl, 2-butynyl and 3-butynyl as well as polyynes like 2, 5-hexadiynyl .
  • C2-C6 alkynyloxy optionally substituted with one or more halogen atoms examples include 2-propynyloxy, 3- chloro-2-propynyloxy and 2-butynyloxy .
  • Cl-C ⁇ alkylthio optionally substituted with one or more halogen atoms examples include methylthio, trifluoromethylthio, ethylthio, propylthio, isopropylthio, butylthio, isobutylthio, sec-butylthio, tert-butylthio, pentylthio and hexylthio.
  • C1-C6 alkylsulfinyl optionally substituted with one or more halogen atoms include methylsulfinyl, trifluoromethylsulfinyl, ethylsulfinyl, propylsulfinyl, isopropylsulfinyl, butylsulfinyl, isobutylsulfinyl, sec-butylsulfinyl, tert-butylsulfinyl, pentylsulfinyl and hexylsulfinyl .
  • the definition includes both sulfoxide enantiomers .
  • C1-C6 alkylsulfonyl optionally substituted with one or more halogen atoms examples include methylsulfonyl, trifluoromethylsulfonyl, ethylsulfonyl, propylsulfonyl, isopropylsulfonyl, butylsulfonyl, isobutylsulfonyl, sec-butylsulfonyl, tert-butylsulfonyl, pentylsulfonyl and hexylsulfonyl .
  • C1-C6 alkylamino examples include methylamino, ethylamino, n-propylamino, isopropylamino, n-butylamino, sec-butylamino, isobutylamino and tert-butylamino .
  • C1-C6 alkylamino optionally substituted with one or more halogen atoms alkylamino examples include methylamino, ethylamino, n-propylamino, isopropylamino, n- butylamino, sec-butylamino, isobutylamino, tert-butylamino, 2-fluoroethyl amino, 2, 2, 2-trifluoroethyl amino, 2,2,3,3,3- pentafluoropropyl amino and 2, 2, 3, 3, 4 , 4 , 4-heptafluoroamino.
  • C2-C8 dialkylamino examples include dimethylamino, diethylamino, ethylmethylamino, di-n-propylamino, diisopropylamino and di-n-butylamino.
  • C2-C8 dialkylamino optionally substituted with one or more halogen atoms examples include dimethylamino, diethylamino, ethylmethylamino, bis (2,2,2- trifluoroethyl) amino, di-n-propylamino, diisopropylamino and di-n-butylamino.
  • C3-C6 cycloalkylamino examples include cyclopropyl amino, cyclobutylamino, cyclopentylamino and cyclohexylamino .
  • C2-C6 alkylcarbonyl examples include acetyl, propionyl, isobutyryl and trimethylacetyl .
  • C2-C6 alkylcarbonyl optionally substituted with one or more halogen atoms include acetyl, trifluoroacetyl, trichloroacetyl, propionyl, pentafluoropropionyl, isobutyryl and trimethylacetyl .
  • C2-C6 alkoxycarbonyl examples include methoxycarbonyl, ethoxycarbonyl, isopropoxycarbonyl and tert-butoxycarbonyl
  • C2-C6 alkoxycarbonyl optionally substituted with one or more halogen atoms examples include methoxycarbonyl, ethoxycarbonyl, 2-fluoroethoxycarbonyl, 2,2, 2-trifluoroethoxycarbonyl, 2,2,2- trichloroethoxycarbonyl, isopropoxycarbonyl and tert- butoxycarbonyl .
  • C2-C6 alkylaminocarbonyl includes methylaminocarbonyl, ethylaminocarbonyl, n- propylaminocarbonylcarbonyl, isopropylaminocarbonyl, n- butylaminocarbonyl, see-butylaminocarbonyl, isobutylaminocarbonyl and tert-butylaminocarbonyl .
  • C2-C6 alkylaminocarbonyl optionally substituted with one or more halogen atoms include methylaminocarbonyl, ethylaminocarbonyl, n- propylaminocarbonyl, isopropylaminocarbonyl, n- butylaminocarbonyl , sec-butylaminocarbonyl , isobutylaminocarbonyl, tert-butylaminocarbonyl, 2- fluoroethylaminocarbonyl, 2,2, 2-trifluoroethylaminocarbonyl, 2,2,3,3, 3-pentafluoropropylcarbonylaminocarbonyl and 2,2,3,3,4,4, 4-heptafluorobutylaminocarbonyl .
  • C3-C8 dialkylaminocarbonyl examples include dimethylaminocarbonyl and diethylaminocarbonyl .
  • C4-C6 cycloalkylaminocarbonyl examples include cyclopropylaminocarbonyl, cyclobutylaminocarbonyl, cyclopentylaminocarbonyl and cyclohexylaminocarbonyl .
  • C3-C6 trialkylsilyl examples include trimthylsilyl, triethylsilyl and tertbutyldimethylsilyl .
  • C3-C6 cycloalkyl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, and (2) C1-C6 alkyl optionally substituted with one or more halogen atoms include cyclopropyl, 2-methylcyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl.
  • phenyl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) hydroxyl, (5) carboxyl, (6) C1-C6 alkyl optionally substituted with one or more halogen atoms, (7) C1-C6 hydroxyalkyl, (8) C1-C6 alkoxy optionally substituted with one or more halogen atoms, (9) C2-C6 cyanoalkyl optionally substituted with one or more halogen atoms, (10) C2-C6 alkoxyalkyl optionally substituted with one or more halogen atoms, (11) C2-C6 alkenyl optionally substituted with one or more halogen atoms, (12) C2-C6 alkynyl optionally substituted with one or more halogen atoms, (13) C3-C6 cycloalkyl optionally substituted with one or more halogen atoms, (14) C1
  • C3-C6 cycloalkylamino (20) C2-C6 alkylcarbonyl, (21) C2-C6 alkoxycarbonyl, (22) C2-C6 alkylaminocarbonyl, (23) C3-C8 dialkylaminocarbonyl, (24) C4-C6 cycloalkylaminocarbonyl and (25) C3-C6 trialkylsilyl include phenyl, 2-fluorophenyl, 3-fluorophenyl, 4-fluorophenyl, 2- chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2-bromophenyl, 2-iodophenyl, 2, 6-difluorophenyl, 2, 6-dichlorophenyl, 2- chloro-6-fluorophenyl, 2-chloro-4-fluorophenyl, 2- cyanophenyl, 3-cyanophenyl, 4-cyanophenyl, 2-nitrophenyl, 2-fluorophenyl,
  • benzyl optionally substituted with one or more substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) hydroxyl, (5) carboxyl, (6) C1-C6 alkyl optionally substituted with one or more halogen atoms, (7) C1-C6 hydroxyalkyl, (8) C1-C6 alkoxy optionally substituted with one or more halogen atoms, (9) C2-C6 cyanoalkyl optionally substituted with one or more halogen atoms, (10) C2-C6 alkoxyalkyl optionally substituted with one or more halogen atoms, (11) C2-C6 alkenyl optionally substituted with one or more halogen atoms, (12) C2-C6 alkynyl optionally substituted with one or more halogen atoms, (13) C3-C6 cycloalkyl optionally substituted with one or more halogen atoms, (14) C1-
  • C7-C9 phenylalkyl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) hydroxyl, (5) carboxyl, (6) C1-C6 alkyl optionally substituted with one or more halogen atoms, (7) C1-C6 hydroxyalkyl, (8) Cl-C ⁇ alkoxy optionally substituted with one or more halogen atoms, (9) C2-C6 cyanoalkyl optionally substituted with one or more halogen atoms, (10) C2-C6 alkoxyalkyl optionally substituted with one or more halogen atoms, (11) C2-C6 alkenyl optionally substituted with one or more halogen atoms, (12) C2-C6 alkynyl optionally substituted with one or more halogen atoms, (13) C3-C6 cycloalkyl optionally substituted with one or more halogen atom
  • C4-C6 cycloalkylaminocarbonyl and (25) C3-C6 trialkylsilyl include benzyl, 1-phenylethyl, 2-phenylethyl, 2-chlorobenzyl, 3- chlorobenzyl, 4-chlorobenzyl, 2-cyanobenzyl, 3-cyanobenzyl, 4-cyanobenzyl, 2-nitrobenzyl, 3-nitrobenzyl, 4-nitrobenzyl, 2-methylbenzyl, 3-methylbenzyl, 4-methylbenzyl, 2- (trifluoromethyl) benzyl, 3- (trifluoromethyl) benzyl, 4- (trifluoromethyl) benzyl, 2-methoxybenzyl, 3-methoxybenzyl and 4-methoxybenzyl .
  • phenoxy optionally substituted with one or more substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) hydroxyl, (5) carboxyl, (6) C1-C6 alkyl optionally substituted with one or more halogen atoms, (7) C1-C6 hydroxyalkyl, (8) Cl-C ⁇ alkoxy optionally substituted with one or more halogen atoms, (9) C2-C6 cyanoalkyl optionally substituted with one or more halogen atoms, (10) C2-C6 alkoxyalkyl optionally substituted with one or more halogen atoms, (11) C2-C6 alkenyl optionally substituted with one or more halogen atoms, (12) C2-C6 alkynyl optionally substituted with one or more halogen atoms, (13) C3-C6 cycloalkyl optionally substituted with one or more halogen atoms, (14) C1-C6
  • C7-C9 phenoxyalkyl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) C1-C6 alkyl optionally substituted with one or more halogen atoms and (5) C1-C6 alkoxy optionally substituted with one or more halogen atoms include phenoxymethyl, phenoxyethyl, 2-chlorophenoxymethyl, 2- chlorophenoxyethyl, 3-chlorophenoxymethyl, 3- chlorophenoxyethyl, 4-chlorophenoxymethyl, A- chlorophenoxyethyl, 2-cyanophenoxymethyl, 2- cyanophenoxyethyl, 3-cyanophenoxymethyl, 3- cyanophenoxyethyl, 4-cyanophenoxymethyl, A- cyanophenoxyethyl, 2-nitrophenoxymethyl, 2- nitrophenoxyethyl, 3-nitrophenoxymethyl, 3- nitrophenoxyethyl,
  • phenylcarbonyl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) hydroxyl, (5) carboxyl, (6) C1-C6 alkyl optionally substituted with one or more halogen atoms, (7) C1-C6 hydroxyalkyl, (8) C1-C6 alkoxy optionally substituted with one or more halogen atoms, (9) C2-C6 cyanoalkyl optionally substituted with one or more halogen atoms, (10) C2-C6 alkoxyalkyl optionally substituted with one or more halogen atoms, (11) C2-C6 alkenyl optionally substituted with one or more halogen atoms, (12) C2-C6 alkynyl optionally substituted with one or more halogen atoms, (13) C3-C6 cycloalkyl optionally substituted with one or more halogen atoms, (1
  • naphthyl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) C1-C6 alkyl optionally substituted with one or more halogen atoms and (5) C1-C6 alkoxy optionally substituted with one or more halogen atoms include 1-naphthyl and 2-naphthyl.
  • Examples of 3- to 8-membered non-aromatic heterocyclic ring optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, and (2) C1-C6 alkyl optionally substituted with one or more halogen atoms include pyrrolidin-1-yl, piperidino, 3, 5-dimethylpiperidino, hexamethyleneimin-1-yl, heptamethyleneimin-1-yl, morpholino, 2, 6-dimethylmorpholino, thiomorpholin-4-yl, 4- methylpiperazin-1-yl, 4- (ethoxycarbonyl) piperazin-1-yl and 4-phenylpiperazin-l-yl .
  • C7-C9 pyridinylalkyl whose pyridine ring is optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) C1-C6 alkyl optionally substituted with one or more halogen atoms, (5) C1-C6 alkoxy optionally substituted with one or more halogen atoms, (6) C1-C6 alkylthio optionally substituted with one or more halogen atoms, (7) C1-C6 alkylsulfinyl optionally substituted with one or more halogen atoms, (8) C1-C6 alkylsulfonyl optionally substituted with one or more halogen atoms, (9) C1-C6 alkylamino optionally substituted with one or more halogen atoms, (10) C2-C6 dialkylamino optionally substituted with one or more halogen atoms, (11)
  • Said ring at the carbon atoms is substituted by one or more independent G 6 , which represents a halogen atom, C1-C6 alkyl optionally substituted with one or more halogen atoms, and C2-C6 alkoxycarbonyl optionally substituted with one or more halogen atoms.
  • R a which is selected from the group consisting of C1-C6 alkyl optionally substituted with one or more halogen atoms, C2-C6 alkoxycarbonyl optionally- substituted with one or more halogen atoms, or a phenyl optionally substituted with one or more independent substituents selected from the group consisting of a halogen atom, cyano, nitro, C1-C6 alkyl optionally substituted with one or more halogen atoms, C1-C6 alkoxy optionally substituted with one or more halogen atoms, Cl- C6 alkylthio optionally substituted with one or more halogen atoms, C1-C6 alkylsulfinyl optionally substituted with one or more halogen atoms, C1-C6 alkylsulfonyl optionally
  • the substituent Q represents Ql, Q2, Q3, Q4 , Q5 or Q6:
  • a 31 , A 32 , A 33 and A 34 represent an oxygen atom, or a sulfur atom; m represents an integer of 0 to 2.
  • Substituents R 6 to R 13 are selected as explained above in the summary of the invention.
  • J represents Jl or J2. Examples for said ring Jl and J2 are shown below as J-1.1 to J-1.8 and J-2.1 to J-2.8.
  • One nitrogen atom is substituted by R 19a (Jl) or R 19b (J2) .
  • Ring carbon atoms are optionally substituted by 1 to 3 substituents R 20a (Jl) or R 2Ob (J2) provided that, when 2 or 3 substituents R 20a (Jl) or R 2Ob (J2) are present, two or more R 20a s and R 20b' s may be the same or different.
  • Substituents R 19a (Jl), R 19b (J2), R 20a (Jl) and R 20b (J2) are selected as explained above in the summary of the invention.
  • Preferred ring systems include J-I.1, J-I.2, J-2.1 and J-2.2; most preferred J-I.1 and J-I.2.
  • Jl Detailed examples of the group represented by Jl include l-phenylpyrazol-5-yl, 1- (2-chlorophenyl) pyrazol-5- yl, 1- (2-pyridinyl)pyrazol-5-yl, 1- (3-chloro-2- pyridinyl) pyrazol-5-yl, a 3-fluoro-l-phenylpyrazol-5-yl, 1- (2-chlorophenyl) -3-fluoropyrazol-5-yl, 3-fluoro-l- (2- pyridinyl) pyrazol-5-yl, 3-fluoro-l- (3-chloro-2- pyridinyl) pyrazol-5-yl, 3-chloro- l-phenylpyrazol-5-yl, 3-chloro-l- (2- chlorophenyl) pyrazol-5-yl, 3-chloro-l- (2- chlorophenyl) pyrazol-5-yl,
  • Examples of the group represented by J2 include 1- methyl-3-phenylpyrazol-4-yl, 3- (2-chlorophenyl) -1- methylpyrazol-4-yl, l-methyl-3- (2-pyridinyl) pyrazol-4-yl, 3- (3-chloro-2-pyridinyl) -l-methylpyrazol-4-yl, l-methyl-5- phenylpyrazol-4-yl, 5- (2-chlorophenyl) -l-methylpyrazol-4-yl, 1-methyl-5- (2-pyridinyl) pyrazol-4-yl, 5- ( 3-chloro-2- pyridinyl) -l-methylpyrazol-4-yl, 3-phenyl-l- (2,2,2- trifluoroethyl) pyrazol-4-yl, 3- (2-chlorophenyl) -1- (2,2,2- trifluoroethyl) pyrazol-4-yl, 3- (2
  • Preferred compounds are:
  • Preferred Compound 1 The compound according to the present compound, an i ⁇ 7-oxide thereof or suitable salt thereof, wherein E is 5- or 6-membered heteroaromatic ring.
  • Preferred Compound 2 The compound according to the Preferred Compound 1, wherein A 1 and A 2 are oxygen atoms,
  • R 1 is a hydrogen atom or alkyl optionally substituted with one or more halogen atoms.
  • Preferred Compound 3 The compound according to the Preferred Compound 2, wherein J is J-I.1, J-I.2, J-2.1, J- 2.2 or J-2.3:
  • R 19a and R 19b represent a hydrogen atom; C1-C6 alkyl optionally substituted with one or more halogen atoms; C3-C6 cycloalkyl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom and (2) C1-C6 alkyl optionally substituted with one or more halogen atoms; ⁇ phenyl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) C1-C6 alkyl optionally substituted with one or more halogen atoms, (5) C1-C6 alkoxy optionally substituted with one or more halogen atoms, (6) C1-C6 alkylthio optionally substituted with one or more halogen atoms, (7) C1-C6 alkylsulfinyl optionally substituted with one or more halogen atoms, (8)
  • R 20a and R 20b represent a halogen atom, cyano, C1-C6 alkyl optionally substituted with one or more halogen atoms, Cl-C ⁇ alkoxy optionally substituted with one or more halogen atoms, C2-C6 cyanoalkyloxy, C2-C6 alkoxyalkyloxy optionally substituted with one or more halogen atoms, C2- C6 alkenyloxy optionally substituted with one or more halogen atoms, C1-C6 alkylthio optionally substituted with one or more halogen atoms, C1-C6 alkylthio optionally substituted with one or more halogen atoms, C1-C6 alky
  • 5- to 6-membered heteroaryl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) Cl-C ⁇ alkyl optionally substituted with one or more halogen atoms and (5) C1-C6 alkoxy optionally substituted with one or more halogen atoms or phenoxy optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) C1-C6 alkyl optionally substituted with one or more halogen atoms and (5) C1-C6 alkoxy optionally substituted with one or more halogen atoms; p represents an integer of 0 to 3, and q represents an integer of 0 to 3 (provided that, when p is an integer of 2 or 3, two or more R 20a' s may be the same or different and, when q is an integer of 2 or 3, two or more R 20b
  • Preferred Compound 4 The compound according to the present compound, an N-oxide thereof or suitable salt thereof, wherein Q is Ql, A 31 is oxygen and
  • R 6 represents a hydrogen atom; C1-C6 alkyl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) C1-C6 alkoxy optionally substituted with one or more halogen atoms, (3) C1-C6 alkylthio optionally substituted with one or more halogen atoms, (4) C1-C6 alkylsulfinyl optionally substituted with one or more halogen atoms, (5) C1-C6 alkylsulfonyl optionally substituted with one or more halogen atoms, (6) C2-C6 dialkylamino optionally substituted with one or more halogen atoms, and (7) C3-C6 cycloalkyl optionally substituted with one or more halogen atoms;
  • C3-C6 cycloalkyl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, and (2) C1-C6 alkyl optionally substituted with one or more halogen atoms; phenyl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) C1-C6 alkyl optionally substituted with one or more halogen atoms, (5) C1-C6 alkoxy optionally substituted with one or more halogen atoms, (6) C1-C6 alkylthio optionally substituted with one or more halogen atoms, (7) C1-C6 alkylsulfinyl optionally substituted with one or more halogen atoms, (8) C1-C6 alkylsulfonyl optionally substituted with one or more halogen atoms, (9) C1-C6 alkyla
  • 5- to 6-membered heteroaryl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) C1-C6 alkyl optionally substituted with one or more halogen atoms and (5) C1-C6 alkoxy optionally- substituted with one or more halogen atoms;
  • 3- to 8-membered non-aromatic heterocyclic optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, and (2) C1-C6 alkyl optionally substituted with one or more halogen atoms or C7-C9 phenylalkyl or C7-C9 phenoxyalkyl : each said phenyl ring optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) C1-C6 alkyl optionally substituted with one or more halogen atoms and (5) C1-C6 alkoxy optionally substituted with one or more halogen atoms.
  • Preferred Compound 5 The compound according to the Preferred Compound 4, wherein A 1 and A 2 are oxygen atoms.
  • Preferred Compound 6 The compound according to the present compound, an N-oxide thereof or suitable salt thereof, wherein Q is Q2 , A 32 is oxygen and R 7 is C1-C6 alkyl optionally substituted with one or more halogen atoms; C2-C6 alkenyl optionally substituted with one or more halogen atoms; C3-C6 cycloalkyl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, and (2) C1-C6 alkyl optionally substituted with one or more halogen atoms; phenyl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) C1-C6 alkyl optionally substituted with one or more halogen atoms, (5) C1-C6 alkoxy optionally substituted with one or more halogen atoms, (6) C1-C6 alkylthio optional
  • 5- to 6-membered heteroaryl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) C1-C6 alkyl optionally substituted with one or more halogen atoms and (5) C1-C6 alkoxy optionally substituted with one or more halogen atoms or C7-C9 phenylalkyl whose ring moiety is optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) C1-C6 alkyl optionally substituted with one or more halogen atoms and (5) C1-C6 alkoxy optionally substituted with one or more halogen atoms .
  • Preferred Compound 7 The compound according to the Preferred Compound 6, wherein A 1 and A 2 are oxygen atoms.
  • Preferred Compound 8 The compound according to the present compound, an 7 ⁇ 7-oxide thereof or suitable salt thereof, wherein Q is Q4 , A 34 is oxygen and
  • R 9 and R 10 independently represent a hydrogen atom; C1-C6 alkyl optionally substituted with one or more halogen atoms; C3-C6 cycloalkyl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, and (2) C1-C6 alkyl optionally substituted with one or more halogen atoms; phenyl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) C1-C6 alkyl optionally substituted with one or more halogen atoms, (5) C1-C6 alkoxy optionally substituted with one or more halogen atoms, (6) C1-C6 alkylthio optionally substituted with one or more halogen atoms, (7) C1-C6 alkylsulfinyl optionally substituted with one or more halogen atoms, (8) Cl-C
  • 5- to 6-membered heteroaryl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) C1-C6 alkyl optionally substituted with one or more halogen atoms and (5) C1-C6 alkoxy optionally substituted with one or more halogen atoms or C7-C9 phenylalkyl whose ring moiety is optionally- substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) C1-C6 alkyl optionally substituted with one or more halogen atoms and (5) C1-C6 alkoxy optionally substituted with one or more halogen atoms .
  • Preferred Compound 9 The compound according to the Preferred Compound 8, wherein A 1 and A 2 are oxygen atoms.
  • Preferred Compound 10 A hydrazide compound represented by the formula (II-l) or (II-2),
  • X a represents a nitrogen atom or CR 20ax ,
  • Y and Z represent independently a nitrogen atom or
  • R 1 represets a hydrogen atom or C1 -C 6 alkyl optionally substituted with one or more halogen atoms
  • R 2 and R 3 independently represent a hydrogen atom, Cl- C6 alkyl optionally substituted with one or more halogen atoms, C2-C6 cyanoalkyl, C1-C6 hydroxyalkyl, C2-C6 alkoxyalkyl optionally substituted with one or more halogen atoms, C2-C6 alkenyl optionally substituted with one or more halogen atoms, C2-C6 alkynyl optionally substituted with one or more halogen atoms, C3-C6 cycloalkyl optionally substituted with one or more halogen atoms, C1-C6 alkylthio optionally substituted with one or more halogen atoms, Cl- C6 alkylsulfinyl optionally substituted with one or more halogen atoms, C1-C6 alkyls
  • R 4a , R 4b and R 4c independently represent a halogen atom, cyano, nitro, hydroxyl, carboxyl, C1-C6 alkyl optionally substituted with one or more halogen atoms, C2-C6 alkoxy optionally substituted with one or more halogen atoms, C2- C6 cyanoalkyl , C2-C6 alkoxyalkyl optionally substituted with one or more halogen atoms, C2-C6 alkenyl optionally substituted with one or more halogen atoms, C2-C6 alkynyl optionally substituted with one or more halogen atoms, C3- C6 cycloalkyl optionally substituted with one or more halogen atoms, C1-C6 alkylthio optionally substituted with one or more halogen atoms, C1-C6 alkylsulfinyl optionally substituted with one or more halogen atoms, C1-C6 alkyl
  • M is a hydrogen atom; C1-C6 alkyl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) C1-C6 alkoxy optionally substituted with one or more halogen atoms, (3) C1-C6 alkylthio optionally substituted with one or more halogen atoms, (4) C1-C6 alkylsulfinyl optionally substituted with one or more halogen atoms, (5) C1-C6 alkylsulfonyl optionally substituted with one or more halogen atoms, (6) C2-C6 dialkylamino optionally substituted with one or more halogen atoms, and (7) C3-C6 cycloalkyl optionally substituted with one or more halogen atoms; C1-C6 alkoxy optionally substituted with one or more halogen atoms; C1-C6 alkylthio optionally substituted with one or more hal
  • 5- to 6-membered heteroaryl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) C1-C6 alkyl optionally substituted with one or more halogen atoms, and (5) C1-C6 alkoxy optionally substituted with one or more halogen atoms; or 3- to 8-membered non-aromatic heterocyclic ring optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, and (2) C1-C6 alkyl optionally substituted with one or more halogen atoms;
  • R 20ax , R 20ay and R 20az represent a halogen atom; cyano ; nitro; thiocyanato; C1-C6 alkyl optionally substituted with one or more halogen atoms; C1-C6 alkoxy optionally substituted with one or more halogen atoms; C2-C6 cyanoalkyloxy; C2-C6 alkoxyalkyloxy optionally substituted with one or more halogen atoms; C2-C6 alkenyloxy optionally substituted with one or more halogen atoms; C2-C6 alkynyloxy optionally substituted with one or more halogen atoms; C1-C6 alkylthio optionally substituted with one or more halogen atoms; C1-C6 alkylsulfinyl optionally substituted with one or more halogen atoms; Cl-C ⁇ alkylsulfonyl optionally substituted with one or more halogen atoms;
  • 5- to 6-membered heteroaryl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) C1-C6 alkyl optionally substituted with one or more halogen atoms and (5) C1-C6 alkoxy optionally substituted with one or more halogen atoms; or phenoxy optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) C1-C6 alkyl optionally substituted with one or more halogen atoms and (5) C1-C6 alkoxy optionally substituted with one or more halogen atoms.
  • Preferred Compound 11 The compound according to the Preferred Compound 10, wherein R 1 is a hydrogen atom, R 2 is a hydrogen atom or C1-C6 alkyl optionally substituted with one or more halogen atoms,
  • R 3 is a hydrogen atom, C1-C6 alkyl optionally substituted with one or more halogen atoms or C2-C6 alkoxycarbonyl,
  • R 4a is a halogen atom or C1-C6 alkyl optionally substituted with one or more halogen atoms,
  • R 4c is a hydrogen atom, a halogen atom, cyano or Cl- C6 alkyl optionally substituted with one or more halogen atoms,
  • X b is a nitrogen atom or CR 21a
  • R 20a ⁇ and R 20ay are i n d e p en dently a hydrogen atom, a halogen atom,- Cl-C ⁇ alkyl optionally substituted with one or more halogen atoms, C1-C6 alkoxy optionally substituted with one or more halogen atoms or C1-C6 alkylthio optionally substituted with one or more halogen atoms
  • R 20az is a hydrogen atom
  • R 21a , R 21b and R 21c are independently selected from the group consisting of a hydrogen atom, a halogen atom or Cl- C ⁇ alkyl optionally substituted with one or more halogen atoms .
  • Preferred Compound 12 The compound according to the Preferred Compound 11, wherein X a and X b are nitrogen atoms, Y is CH and Z is a nitrogen atom.
  • Preferred Compound 13 The compound according to the Preferred Compound 11, wherein X a and X b are nitrogen atoms, Y is a nitrogen atom Z is CH and.
  • Preferred Compound 14 The compound according to the Preferred Compound 11, wherein R 4b is a hydrogen atom.
  • Preferred Compound 15 The compound according to the Preferred Compound 14, wherein M is a hydrogen atom, C1-C6 alkyl, C1-C6 alkoxy, amino, C1-C6 alkylamino or C2-C8 dialkylamino .
  • Preferred Compound 16 The compound according to the Preferred Compound 15, wherein
  • R 2 is a hydrogen atom, methyl or ethyl
  • R 3 is a hydrogen atom, methyl, ethyl or methoxycarbonyl
  • R 4a is methyl, chloro, bromo or iodo
  • R 4c is hydrogen, fluoro, chloro, bromo, iodo or cyano, R 20ay ⁇ 3 c h]_ orO/ bromo, iodo, trifluoromethyl or pentafluoroethoxy,
  • R 22b is a hydrogen atom
  • R 22c is chloro or bromo
  • M is hydrogen, methoxy, ethoxy, methylamino or dimethylamino .
  • Preferred Compound 17 The compound of the Preferred Compound 16, wherein R 2 is a hydrogen atom, R 3 is methyl or ethyl and M is a hydrogen atom.
  • Preferred Compound 18 The compound of the Preferred Compound 17, wherein R 2 and R 3 are independently hydrogen, methyl or ethyl and
  • M is methoxy or ethoxy.
  • Preferred Compound 19 A hydrazide compound represented by the formula (II-l),
  • X a , Y, Z, R 1 , R 2 , R 3 , R 4a , R 4b , R 4c , M, R 19ax , R 20ax , R 20ay , and R 20az are discribed above.
  • Preferred Compound 20 The compound according to the Preferred Compound 19, wherein R 1 is a hydrogen atom, R 2 is a hydrogen atom or C1-C6 alkyl optionally substituted with one or more halogen atoms, R 3 is a hydrogen atom, Cl-C ⁇ alkyl optionally substituted with one or more halogen atoms or C2-C6 alkoxycarbonyl ,
  • R 4a is a halogen atom or Cl-C ⁇ alkyl optionally substituted with one or more halogen atoms
  • R 4c is a hydrogen atom, a halogen atom, cyano or 1-C6 alkyl optionally substituted with one or more halogen atoms
  • R 19a is
  • R 20a ⁇ and R 20ay are i nc ⁇ e p enc ⁇ en tIy a hydrogen atom, a halogen atom, C1-C6 alkyl optionally substituted with one or more halogen atoms, C1-C6 alkoxy optionally substituted with one or more halogen atoms or C1-C6 alkylthio optionally substituted with one or more halogen atoms, R 20az is a hydrogen atom,
  • R 21a , R 21b and R 21c are independently selected from the group consisting of a hydrogen atom, a halogen atom or Cl- C6 alkyl optionally substituted with one or more halogen atoms .
  • Preferred Compound 21 The compound according to the Preferred Compound 20, wherein X a and X b are nitrogen atoms,
  • Y is CH
  • Z is a nitrogen atom.
  • Preferred Compound 22 The compound according to the Preferred Compound 20, wherein X a and X b are nitrogen atoms, Y is a nitrogen atom Z is CH and.
  • Preferred Compound 23 The compound according to the Preferred Compound 20, wherein R 4b is a hydrogen atom.
  • Preferred Compound 24 The compound according to the Preferred Compound 23, wherein M is a hydrogen atom, Cl-C ⁇ alkyl, C1-C6 alkoxy, amino, C1-C6 alkylamino or C2-C8 dialkylamino .
  • Preferred Compound 25 The compound according to the Preferred Compound 24, wherein
  • R 2 is a hydrogen atom, methyl or ethyl
  • R 3 is a hydrogen atom, methyl, ethyl or methoxycarbonyl
  • R 4a is methyl, chloro, bromo or iodo
  • R 4c is hydrogen, fluoro, chloro, bromo, iodo or cyano
  • R 20ay is chloro, bromo, iodo, trifluoromethyl or pentafluoroethoxy
  • R 22b is a hydrogen atom
  • R 22c is chloro or bromo
  • M is hydrogen, methoxy, ethoxy, methylamino or dimethylamino .
  • Preferred Compound 26 The compound of the Preferred Compound 25, wherein R 2 is a hydrogen atom, R 3 is methyl or ethyl and M is a hydrogen atom.
  • Preferred Compound 27 The compound of the Preferred Compound 26, wherein R 2 and R 3 are independently hydrogen, methyl or ethyl and
  • M is methoxy or ethoxy.
  • This invention further pertains:
  • a pesticide comprising the present compound or , an N- oxide thereof or suitable salt thereof as an active ingredient .
  • a method of controlling a pest which comprises applying the present compound, an iV-oxide thereof or suitable salt thereof directly to a pest, or to a place where a pest inhabits.
  • the present compound can be produced, for example, by the following Process A-I to Process C-I.
  • Process A-I Process A-I
  • R 1 , R 2 , R 3 , R 4 , A 1 , A 2 , J and n are as defined above
  • E represents, together with the two contiguous linking carbon atoms, a 5- or 6-membered heteroaromatic ring system or a 8 , 9 or 10-membered fused heterobicyclic ring system
  • Q' represents a group selected from the group consisting of Ql to Q6 (provided that the compound wherein Q' is Q4 , and R 8 and R 9 are a hydrogen atom is excluded) (hereinafter, referred to as the compound (I)) can be produced by reacting a compound represented by the formula (2) : wherein R 1 , R 2 , R 3 , R 4 , A 1 , A 2 , J and n are as defined above (hereinafter, referred to as the compound (2)), and a compound represented by the formula (3) : L 1 —Q 1 ( 3) wherein Q' is as defined above, and L 1 represents a halogen
  • the reaction is performed in the presence or the absence of a solvent.
  • the solvent to be used in the reaction include ethers such as 1,4-dioxane, diethyl ether, tetrahydrofuran, methyl tert-butyl ether, and the like, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1, 2-dichloroethane, chlorobenzene, and the like, hydrocarbons such as toluene, benzene, xylene, and the like, nitriles such as acetonitrile and the like, aprotic polar solvents such as N, N-dimethylformamide, N-methlpyrrolidone, 1, 3-dimethyl-2- imidadzolidinone, dimethyl sulfoxide, and the like, and a mixture thereof.
  • the amount of the compound (3) to be used in the reaction is usually 1 to 2 mols per 1 mol of the
  • the reaction is performed in the presence of a base, if necessary.
  • a base include nitrogen- containing heterocyclic compounds such as pyridine, picoline, 2, 6-lutidine, 1, 8-diazabicyclo [5, 4, 0] 7-undecene (DBU), 1, 5-diazabicyclo[4, 3, 0] 5-nonene (DBN), and the like, tertiary amines such as triethylamine, N, N- diisopropylethylamine, and the like, and inorganic bases such as potassium carbonate, sodium hydride, and the like.
  • DBU 1, 8-diazabicyclo [5, 4, 0] 7-undecene
  • DBN 1, 5-diazabicyclo[4, 3, 0] 5-nonene
  • tertiary amines such as triethylamine, N, N- diisopropylethylamine, and the like
  • inorganic bases such as potassium carbonate, sodium
  • the amount of the base when the reaction is performed in the presence of the base is usually 1 to 2 mols per 1 mol of the compound (2), while the base may be used in an excess amount in case that the base used is liquid under the reaction conditions such as pyridine, and the like.
  • the reaction temperature is usually in a range of 0 to 100 0 C, and the reaction time is usually in a range of 0.1 to 24 hours.
  • the compound (1-i) can be isolated by pouring the reaction mixture into water and extracting the mixture with an organic solvent, or collecting a deposited precipitate by filtration.
  • the isolated compound (1-i) may be further purified by recrystallization, chromatography, or the like.
  • R 9a represents C1-C6 alkyl optionally substituted with at least one halogen atom; C2-C6 alkoxyalkyl optionally substituted with at least one halogen atom; C2-C6 alkenyl optionally substituted with at least one halogen atom; 3-C6 alkynyl optionally substituted with at least one halogen atom; C3-C6 cycloalkyl optionally- substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom and (2) C1-C6 alkyl group; a phenyl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom (2) cyano group, (3) nitro group, (4) Cl-C ⁇ alkyl optionally substituted with at least one halogen atom, (5) C
  • C1-C6 alkyl optionally substituted with at least one halogen atom and (5) C1-C6 alkoxy optionally substituted with at least one halogen atom (hereinafter, referred to as the compound (1-ii)) can be produced by reacting the compound (2) with a compound represented by the formula (4) :
  • a 34 ⁇ C N-R 93 (4) wherein A 34 and R 9a are as defined above (hereinafter, referred to as the compound (4)) .
  • the reaction is performed in the presence or the absence of a solvent.
  • the solvent to be used in the reaction include ethers such as 1,4-dioxane, diethyl ether, tetrahydrofuran, methyl tert-butyl ether, and the like, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1, 2-dichloroethane, chlorobenzene, and the like, hydrocarbons such as toluene, benzene, xylene, and the like, nitriles such as acetonitrile, and the like, aprotic polar solvents such as N,N-dimethylformamide, N-methylpyrrolidone, 1, 3-dimethyl-2- imidazolidinone, dimethyl sul
  • the amount of the compound (4) used in the reaction is usually 1 to 2 mols per 1 mol of the compound (2) .
  • the reaction temperature is usually in a range of 0 to 100 0 C, and the reaction time is a usually a range of 0.1 to 24 hours.
  • the compound (1-ii) can be isolated by pouring the reaction mixture into water, and extracting the mixture with an organic solvent, or collecting a deposited precipitate by filtration.
  • the isolated compound (1-ii) may be further purified by recrystallization, chromatography, or the like.
  • Process A-3 Among the present compounds, a compound represented by the formula ( 1-iii ) :
  • R 1 , R 2 , R 3 , R 4 , A 1 ' A 2 , A 34 , J and n are as defined above (hereinafter, referred to as the compound (I-iii)) can be produced by reacting the compound (2) and a cyanate or a thiocyanate.
  • the reaction is performed in the presence of a solvent.
  • the solvent used in the reaction include acids such as organic acids such as acetic acids, and the like and mineral acids such as hydrochloric acid, and the like, as well as a mixture of these acids and water, chloroform, or the like.
  • the amount of the cyanate or the thiocyanate used in the reaction is usually 1 to 2 mols per 1 mol of the compound (2) .
  • the reaction temperature is usually in a range of 0 to 100 0 C, and the reaction time is usually in a range of 0.1 to 24 hours.
  • Examples of the cyanate or the thiocyanate include potassium cyanate, sodium cyanate, ammonium cyanate, potassium thiocyanate, sodium thiocyanate and ammonium thiocyanate .
  • the compound (I-iii) can be isolated by pouring the reaction mixture into water and extracting the mixture with an organic solvent, or collecting a deposited precipitate by filtration.
  • the isolated Compound (I-iii) may be further purified by recrystallization, chromatography, or the like.
  • the present compound can be produced by reacting a compound represented by the formula (6):
  • R 1 , R 2 , R 3 , R 4 , A 2 , Q and n are as defined above
  • N 1 (7) A 1 wherein A and J are as define above, and L represents a halogen atom (hereinafter, referred to as the compound (7)).
  • the reaction is performed in the presence or the absence of a solvent.
  • the solvent used in the reaction include ethers such as 1,4-dioxane, diethyl ether, tetrahydrofuran, methyl tert-butyl ether, and the like, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1, 2-dichloroethane, chlorobenzene, and the like, hydrocarbons such as toluene, benzene, xylene, and the like, nitriles such as acetonitrile, and the like, aprotic polar solvents such as N, N-dimethylformamide, N-methylpyrrolidone, 1, 3-dimethyl-2- imidazolidinone, dimethyl sulfoxide, and the like, and a mixture thereof.
  • the amount of the compound (7) used in the reaction is usually 1 to 2 mols per 1 mol of the compound (6) .
  • the reaction is performed in the presence of a base, if necessary.
  • a base include nitrogen- containing heterocyclic compounds such as pyridine, picoline, 2, 6-lutidine, 1, 8-diazabicyclo [5, 4 , 0] 7-undecene (DBU), l,5-diazadicyclo[4,3,0] 5-nonene (DBN), and the like, tertiary amines such as triethylamine, N, N- diisopropylethylamine, and the like, and inorganic bases such as potassium carbonate, sodium hydride, and the like.
  • DBU 1, 8-diazabicyclo [5, 4 , 0] 7-undecene
  • DBN l,5-diazadicyclo[4,3,0] 5-nonene
  • tertiary amines such as triethylamine, N, N- diisopropylethylamine, and the like
  • the amount of the base when the reaction is performed in the presence of the base is usually 1 to 2 mole per 1 mol of the compound (6), while the base may be used in an excess amount in case that the base used is liquid under the reaction conditions such as pyridine, and the like.
  • the reaction temperature is usually in a range of 0 to 100 0 C, and the reaction time is usually in a range of 0.1 to 24 hours .
  • the present compound can be isolated by pouring the reaction mixture into water, and extracting the mixture with an organic solvent, or collecting a deposited precipitation by filtration.
  • the isolated present compound may be further purified by recrystallization, chromatography, or the like.
  • R 1 , R 2 , R 3 , R 4 , A 2 , J, Q and n are as defined above (hereinafter referred to as the compound (I-iv) ) can be produced by reacting the compound (6) and a compound represented by the formula (8): wherein J is as defined above (hereinafter, referred to as the compound (8)) in the presence of a dehydrating agent.
  • the reaction is performed in the presence or the absence of a solvent.
  • the solvent to be used in the reaction include ethers such as 1,4-dioxane, diethyl ether, tetrahydrofuran, methyl tert-butyl ether, and the like, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1, 2-dichloroethane, chlorobenzene, and the like, hydrocarbons such as toluene, benzene, xylene, and the like, nitriles such as acetonitrile, and the like, aprotic polar solvents such as N,N-dimethylformamide, N-methylpyrrolidone, 1, 3-dimethyl-2- imidazolidinone, dimethyl sulfoxide, and the like, and a mixture thereof.
  • the amount of the compound (8) used in the reaction is usually 1 to 2 mols per 1 mol of the compound (6) .
  • Examples of the dehydrating agent to be used in the reaction include carbodiimides such as dicyclohexylcarbodiimide (DCC), l-ethyl-3- (3- dimethylaminopropyl) carbodiimide hydrochloride (WSC), and the like.
  • the amount of the dehydrating agent to be used is usually 1 to 2 mols per 1 mol of the compound (6) .
  • the reaction temperature is usually in a range of 0 to 100 0 C, and the reaction time is usually in a range of 0.1 to 24 hours.
  • the compound (I-iv) can be isolated by pouring the reaction mixture into water, and extracting the mixture with an organic solvent, or collecting a deposited precipitate by filtration.
  • the isolated compound (1-iv) may be further purified by recrystallization, chromatography, or the like.
  • R 2 , R 3 , R 4 , J, Q and n are as defined above
  • the compound (1-v) (hereinafter, referred to as the compound (1-v)) can be produced by reacting a compound represented by the formula (9) :
  • R 4 , J and n are as defined above (hereinafter, referred to as the compound (9) ) and a compound represented by the formula (10) : wherein R 2 , R 3 and Q are as defined above (hereinafter, referred to as the compound (10)).
  • the reaction is performed in the presence or the absence of a solvent.
  • solvent used in the reaction examples include ethers such as 1,4-dioxane, diethyl ether, tetrahydrofuran, methyl tert-butyl ether, and the like, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1, 2-dichloroethane, chlorobenzene, and the like, hydrocarbons such as toluene, benzene, xylene, and the like, nitriles such as acetonitrile, and the like, aprotic polar solvents such as N,N-dimethylformamide, N-methylpyrrolidone, 1, 3-dimethyl-2- imidaozolidinone, dimethyl sulfoxide, and the like, and a mixture thereof.
  • ethers such as 1,4-dioxane, diethyl ether, tetrahydrofuran, methyl tert-butyl ether, and the
  • the amount of the compound (10) to be used in the reaction is usually 1 to 20 mols per 1 mol of the compound (9).
  • the reaction temperature is usually in a range of 0 to 100 0 C, and the reaction time is usually in a range of 0.1 to 48 hours.
  • the compound (1-v) can be isolated by pouring the reaction mixture into water, and extracting the mixture with an organic solvent, or collecting a deposited precipitate by filtration.
  • the isolated compound (1-v) may be further purified by recrystallization, chromatography, or the like.
  • Process C-2 Among the present compounds, a compound represented by the formula (1-vi) :
  • R 1 a represents C1-C6 alkyl optionally substituted with at least one halogen atom; C2-C6 cyanoalkyl group; C2-C6 alkoxyalkyl optionally substituted with at least one halogen atom; C2- C6 alkenyl optionally substituted with at least one halogen atom; C3-C6 alkynyl optionally substituted with at least one halogen atom; or C7-C9 phenylalkyl in which a benzene ring part may be substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano group, (3) nitro group, (4) Cl-C ⁇ alkyl optionally substituted with at least one halogen atom and (5) Cl-C ⁇ alkoxy optionally substituted with at least one halogen atom (hereinafter, referred to as
  • the reaction is performed in the presence or the absence of a solvent.
  • the solvent to be used in the reaction include ethers such as 1,4-dioxane, diethyl ether, tetrahydrofuran, methyl tert-butyl ether, and the like, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1, 2-dichlorethane, chlorobenzene, and the like, hydrocarbons such as toluene, benzene, xylene, and the like, nitriles such as acetonitrile, and the like, aprotic polar solvents such as N, N-diethylformamide, N-methylpyrrolidone, 1, 3-dimethyl-2- imidazolidinone, dimethyl sulfoxide, and the like, and a mixture thereof.
  • the amount of the compound (10) to be used in the reaction is usually 1 to 2 mols per 1 mol of the compound
  • the reaction is performed in the presence of a base, if necessary.
  • a base include nitrogen- containing heterocyclic compounds such as pyridine, picoline, 2, 6-lutidine, 1, 8-diazabicyclo [5, 4 , 0] 7-undecene (DBU), 1, 5-diazabicyclo[4, 3, 0] 5-nonene (DBN), and the like, tertiary amines such as triethylamine, N, N- diisopropylethylamine, and the like, and inorganic bases such as potassium carbonate, sodium hydride, and the like.
  • DBU 1, 8-diazabicyclo [5, 4 , 0] 7-undecene
  • DBN 1, 5-diazabicyclo[4, 3, 0] 5-nonene
  • tertiary amines such as triethylamine, N, N- diisopropylethylamine, and the like
  • inorganic bases such as potassium
  • the amount of the base to be used when the reaction is performed in the presence of the base is usually 1 to 2 mols per 1 mol of the compound (11), while the base may be used in an excess amount in the case that the base used is liquid under the reaction conditions such as pyridine and the like.
  • the reaction temperature is usually in a range of 0 to
  • reaction time 100 0 C, and the reaction time is usually in a range of 0.1 to 24 hours.
  • the compound (1-vi) can be isolated after pouring the reaction mixture into water, and extracting the mixture with an organic solvent, or collecting a deposited precipitate by filtration.
  • the isolated compound (1-vi) may be further purified by recrystallization, chromatography or the like.
  • the compound (1-vi) can also be produced by reacting a compound represented by the formula (12) : wherein R 4 , R 1 a ' A 1 , J and n are as defined above (hereinafter, referred to as Compound (12)) and the compound (10) in the presence of a dehydrating agent.
  • the reaction is performed in the presence or the absence of a solvent.
  • solvent to be used in the reaction examples include ethers such as 1,4-dioxane, diethyl ether, tetrahydrofuran, methyl tert-butyl ether, and the like, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1, 2-dichlroethane, chlorobenzene, and the like, hydrocarbons such as toluene, benzene, xylene, and the like, nitriles such as acetonitrile, and the like, aprotic polar solvents such as N, N-dimethylformamide, N-methylpyrrolidone, 1, 3-dimethyl-2- imidazolidinone, dimethyl sulfoxide, and the like, and a mixture thereof.
  • ethers such as 1,4-dioxane, diethyl ether, tetrahydrofuran, methyl tert-butyl ether,
  • the amount of the compound (10) used in the reaction is usually 1 to 2 mols per 1 mol of the compound (12) .
  • Examples of the dehydrating agent used in the reaction include carbodiimides such as dicyclohexylcarbodiimide (DCC) , l-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (WSC), and the like.
  • the amount of the dehydrating agent to be used is usually 1 to 2 mols per 1 mol of the compound (12) .
  • the reaction temperature is usually in a range of 0 to 100 0 C, and the reaction time is usually in a range of 0.1 to 24 hours.
  • the compound (1-vi) can be isolated by pouring the reaction mixture into water and extracting the mixture with an organic solvent, or collecting a deposited precipitate by filtration.
  • the isolated compound (1-vi) may be further purified by recrystallization, chromatography, or the like.
  • R , R , R 4 , J and n are as defined above (hereinafter, referred to as the compound (2-i)) can be produced by reacting the compound (9) and a compound represented by the formula (13) : wherein R 2 and R 3 are as defined above (hereinafter, referred to as the compound (13)). The reaction is performed in the presence or the absence of a solvent.
  • solvent used in the reaction examples include ethers such as 1,4-dioxane, diethyl ether, tetrahydrofuran, methyl tert-butyl ether, and the like, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1, 2-dichloroethane, chlorobenzene and the like, hydrocarbons such as toluene, benzene, xylene and the like, nitriles such as acetonitrile, and the like, aprotic polar solvents such as N, N- dimethylformamide, N-methylpyrrolidone, 1, 3-dimethyl-2- imidazolidinone, dimethyl sulfoxide, and the like, alcohols such as methanol, ethanol, 2-propanol, and the like, and a mixture thereof.
  • ethers such as 1,4-dioxane, diethyl ether, tetrahydro
  • the amount of the compound (13) to be used in the reaction is usually 1 to 5 mols per 1 mol of the compound (9) .
  • the reaction temperature is usually in a range of -50 to 100 0 C, and the reaction time is usually in a range of 0.1 to 24 hours.
  • the compound (2-i) can be isolated by pouring the reaction mixture into water, and extracting the mixture with an organic solvent, or collecting a deposited precipitate by filtration.
  • the isolated compound (2-i) may be further purified by recrystallization, chromatography, or the like.
  • R , J and n are as defined above (hereinafter, referred to as the compound (14)) and the compound (13).
  • the reaction is performed in the presence or the absence of a solvent.
  • the solvent to be used in the reaction include ethers such as 1,4-dioxane, diethyl ether, tetrahydrofuran, methyl tert-butyl ether, and the like, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1, 2-dichloroethane, chlorobenzene and the like, hydrocarbons such as toluene, benzene, xylene, and the like, nitriles such as acetonitrile, and the like, aprotic polar solvents such as N, N-dimethylformamide, N-methylpyrrolidone, 1, 3-dimethyl-2- imidazolidinone, dimethyl sulfoxide, and the like, alcohols such as methanol, ethanol, 2-propanol, and the like, and a mixture thereof.
  • the amount of the compound (13) to be used in the reaction is usually 1 to 5 mols per 1 mol of the compound (14) .
  • the reaction temperature is usually in a range of -50 to 100 0 C, and the reaction time is usually in a range of 0.1 to 24 hours.
  • the compound (2-ii) can be isolated by pouring the reaction mixture into water, and extracting the mixture with an organic solvent, or collecting a deposited precipitate by filtration.
  • the isolated compound (2-ii) may be further purified by recrystallization, chromatography, or the like.
  • Reference Process 3 Among the compound (2), a compound represented by the formula ( 2-iii ) :
  • R 1 a , R 2 , R 3 , R 4 , A 1 , J and n are as defined above (hereinafter, referred to as the compound (2-iii)) can be produced by reacting the compound (11) and the compound (13) .
  • the reaction is performed in the presence or the absence of a solvent.
  • the solvent used in the reaction include ethers such as 1,4-dioxane, diethyl ether, tetrahydrofuran, methyl tert-butyl ether, and the like, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1, 2-dichloroethane, chlorobenzene, and the like, hydrocarbons such as toluene, benzene, xylene, and the like, nitriles such as acetonitrile, and the like, aprotic polar solvents such as N, N-dimethylformamide, N-methylpyrrolidone, 1, 3-dimethyl-2- imidazolidinone, dimethyl sulfoxide, and the like, and a mixture thereof.
  • the amount of Compound (13) used in the reaction is usually 2 to 10 mols per 1 mol of the compound (11) .
  • the reaction temperature is usually in a range of -50 to 100 0 C, and the reaction time is in a range of 0.1 to 24 hours .
  • the compound (2-iii) can be isolated by pouring the reaction mixture into water, and extracting the mixture with an organic solvent, or collecting a deposited precipitate by filtration.
  • the isolated compound (2-iii) may be further purified by recrystallization, chromatography, or the like.
  • Reference Process 4 The compound (9) can be produced by reacting a compound represented by the formula (16) .
  • R 4 and n are as defined above (hereinafter, referred to as the compound (16)) and a compound represented by the formula (7') :
  • the reaction is performed in the presence or the absence of a solvent in the presence of a base.
  • the solvent to be used in the reaction include ethers such as 1,4-dioxane, diethyl ether, tetrahydrofuran, methyl tert-butyl ether, and the like, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1, 2-dichloroethane, chlorobenzene, and the like, hydrocarbons such as toluene, benzene, xylene, and the like, nitriles such as acetonitrile, and the like, aprotic polar solvents such as N, N-dimethylformamide, N-methylpyrrolidone, 1, 3-dimethyl-2-imidazolidinone, dimethyl sulfoxide, and the like, and a mixture thereof.
  • the amount of the compound (7') used in the reaction is usually 0.5 to 2 mols per 1 mol of the compound (16) .
  • Examples of the base to be used in the reaction include nitrogen-containing heterocyclic compounds such as pyridine, picoline, 2, 6-lutidine, 1, 8-diazabicyclo [5, 4 , 0] 7- undecene (DBU) , 1, 5-diazabicyclo [4 , 3, 0] 5-nonene (DBN), and the like, tertiary amines such as triethylamine, N, N- diisopropylethylamine, and the like, and inorganic bases such as potassium carbonate, sodium hydride, and the like.
  • nitrogen-containing heterocyclic compounds such as pyridine, picoline, 2, 6-lutidine, 1, 8-diazabicyclo [5, 4 , 0] 7- undecene (DBU) , 1, 5-diazabicyclo [4 , 3, 0] 5-nonene (DBN), and the like
  • tertiary amines such as triethylamine, N, N- di
  • the amount of the base to be used is usually 1 to 2 mols per 1 mol of the compound (16), while the base may be used in an excess amount in case that the base is liquid under the reaction conditions such as pyridine, and the like.
  • the reaction temperature is usually in a range of 50 to 15O 0 C, and the reaction time is usually in a range of 1 to 24 hours.
  • the compound (9) can be isolated by pouring the reaction mixture into water, and extracting the mixture with an organic solvent, or collecting a deposited precipitates by filtration.
  • the isolated compound (9) may be further purified by recrystallization, chromatography, or the like.
  • Reference Process 5 The compound (9) can be produced by reacting a compound represented by the formula (17) :
  • R 4 and n are as defined above (hereinafter, referred to as Compound (17)) and the compound (7').
  • the reaction is performed in the presence or the absence of a solvent.
  • the solvent to be used in the reaction include ethers such as 1,4-dioxane, diethyl ether, tetrahydrofuran, methyl tert-butyl ether, and the like, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1, 2-dichloroethane, chlorobenzene, and the like, hydrocarbons such as toluene, benzene, xylene, and the like, nitriles such as acetonitrile, and the like, aprotic polar solvents such as N,N-dimethylformamide, N-methylpyrrolidone, 1, 3-dimethyl-2- imidazolidinone, dimethyl sulfoxide, and the like, and a mixture
  • This step is performed by reacting the compound (17) and the compound (7') in the presence of a base.
  • the amount of the compound (7') to be used in this step is usually 1 to 2 mols per 1 mol of the compound (17) .
  • the base include nitrogen-containing heterocyclic compounds such as pyridine, picoline, 2,6- lutidine, 1, 8-diazabicyclo [5, 4 , 0] 7-undecene (DBU), 1,5- diazabicyclo [4 , 3, 0] 5-nonene (DBN), and the like, tertiary amines such as triethylamine, N, N-diisopropylethylamine, and the like, and inorganic bases such as potassium carbonate, sodium hydride, and the like.
  • the amount of the base to be used is usually 1 to 2 mols per 1 mol of the compound (17) .
  • the reaction temperature of this step is usually in a range of 0 to 50 0 C, and the reaction time is usually in a range of 0.1 to 24 hours.
  • Step 5-2 After completion of this step, usually, the reaction mixture is used as it is in the next step 5-2. Step 5-2
  • This step is performed by reacting the reaction mixture in the step 5-1 and a sulfonyl halide in the presence of a base.
  • a sulfonyl halide examples include methanesulfonyl chloride, p-toluenesulfonyl chloride, and trifluoromethanesulfonyl chloride.
  • the amount of the sulfonyl halide to be used in this step is usually 1 to 2 mols per 1 mol of the compound (17) used in the step 5-1.
  • Examples of the base include the same bases as those described with respect to the step 5-1.
  • the amount of the base is usually 2 to 4 mols per 1 mol of the compound (17) used in the step 5-1.
  • the reaction temperature of this step is usually in a range of 0 to 50 0 C, and the reaction time is usually in a range of 0.1 to 24 hours.
  • the compound (9) can be isolated by pouring the reaction mixture into water, followed by conventional extraction with an organic solvent.
  • the isolated compound (9) may be further purified by recrystallization, chromatography, or the like.
  • the compound (14) can be produced by reacting the compound (9) with a thiocarbonylation agent.
  • the reaction is performed in the presence or the absence of a solvent.
  • the solvent to be used in the reaction include ethers such as 1,4-dioxane, diethyl ether, tetrahydrofuran, methyl tert-butyl ether, diglyme, and the like, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1,2- dichloroethane, chlorobenzene, and the like, hydrocarbons such as toluene, benzene, xylene, and the like, nitriles such as acetonitrile, and the like, pyridines such as pyridine, picoline, lutidine, and the like, and a mixture thereof.
  • Examples of the thiocarbonylation agent to be used in the reaction include diphosphorus pentasulfide, a Lawesson's reagent (2, 4-bis- (4-methoxyphenyl) -1, 3-dithia- 2, 4-diphosphetane 2, 4-disulfide) , and the like.
  • the amount of the thiocarbonylation agent to be used in the reaction is usually 1 to 3 mols per 1 mol of the compound ( 9) .
  • the reaction temperature is usually in a range of 0 0 C to 200 0 C, and the reaction time is usually in a range of 1 to 24 hours.
  • the compound (14) can be isolated by collecting a precipitate deposited in the reaction mixture by filtration, or extracting the reaction mixture with an organic solvent.
  • the isolated compound (14) may be further purified by recrystallization, chromatography, or the like.
  • the compound (11) can be produced by reacting the compound (12) with a halogenating agent.
  • the reaction is performed in the presence or the absence of a solvent.
  • the solvent to be used in the reaction include ethers such as 1,4-dioxane, diethyl ether, tetrahydrofuran, methyl tert-butyl ether, and the like, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1, 2-dichloroethane, chlorobenzene, and the like, hydrocarbons such as toluene, benzene, xylene, and the like, nitriles such as acetonitrile, and the like, aprotic polar solvents such as N, N-dimethylformamide, N-methylpyrrolidone, 1, 3-dimethyl-2- imidazolidinone, dimethyl sulfoxide, and the like, and a mixture thereof.
  • halogenating agent examples include thionyl chloride, thionyl bromide, phosphorus oxychloride, phosphorus oxybromide, phosphorus pentachloride, oxalyl chloride, and phosgene.
  • the amount of the halogenating agent to be used in the reaction is usually 1 to 2 mols per 1 mol of the compound (12) and, in some cases, the halogenating agent may be used in an excess amount.
  • the reaction temperature is usually in a range of 0 0 C to 150 0 C, and the reaction time is usually in a range of 0.1 to 24 hours.
  • the compound (11) can be isolated by collecting a precipitate deposited in the reaction mixture, or concentrating the reaction mixture.
  • the isolated compound (11) is usually used as it is in the next step and, if necessary, may be further purified by recrystallization, or the like.
  • the compound (12) can be produced by reacting a compound represented by the formula (18'):
  • R 1"3 , R 4 and n are- as defined above (hereinafter, referred to as the compound (18')) and the compound (7).
  • the reaction is performed in the presence or the absence of a solvent.
  • the solvent used in the reaction include ethers such as 1,4-dioxane, diethyl ether, tetrahydrofuran, methyl tert-butyl ether, and the like, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1, 2-dichloroethane, chlorobenzene, and the like, hydrocarbons such as toluene, benzene, xylene, and the like, nitriles such as acetonitrile, and the like, aprotic polar solvents such as N, N-dimethylformamide, N-methylpyrrolidone, 1, 3-dimethyl-2- imidazolidinone, dimethyl sulfoxide, and the like, and a mixture thereof.
  • the amount of the compound (7) to be used in the reaction is usually 1 to 2 mols per 1 mol of the compound (18') .
  • the reaction is performed in the presence of a base.
  • the base to be used include nitrogen-containing heterocyclic compounds such as pyridine, picoline, 2,6- lutidine, 1, 8-diazabicyclo [5, 4 , 0] 7-undecene (DBU), 1,5- diazabicyclo [4 , 3, 0] 5-nonene (DBN), and the like, tertiary amines such as triethylamine, N,N-diisopropylethylamine, and the like, inorganic bases such as potassium carbonate, sodium hydride, and the like.
  • the amount of the base to be used is usually 1 to 2 mols per 1 mol of the compound (18') .
  • the reaction temperature is usually in a range of 0 to 50 0 C, and the reaction time is usually in range of 0.1 to 24 hours.
  • the compound (12) can be isolated by pouring the reaction mixture into water, followed by conventional extraction with an organic solvent, or collecting a deposited precipitate by filtration.
  • the isolated compound (12) may be further purified by recrystallization, chromatography, or the like.
  • the compound (6) can be produced by reacting a compound represented by the formula (20) :
  • R 1 , R 4 and n are as defined above (hereinafter, referred to as the compound 20)) and the compound (10).
  • the reaction is performed in the presence or the absence of a solvent.
  • the solvent used in the reaction include ethers such as 1,4-dioxane, diethyl ether, tetrahydrofuran, methyl tert-butyl ether, and the like, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1, 2-dichloroethane, chlorobenzene, and the like, hydrocarbons such as toluene, benzene, xylene, and the like, nitriles such as acetonitrile, and the like, aprotic polar solvents such as N, N-dimethylformamide, N-methylpyrrolidone, 1, 3-dimethyl-2- imidazolidinone, dimethyl sulfoxide, and the like, alcohols such as methanol, ethanol, isopropyl alcohol, and the like, and a mixture thereof.
  • the reaction temperature is usually in a range of -20 to 150 0 C, and the reaction time is usually in a range of 0.1 to 24 hours.
  • the compound (20) can be isolated by pouring the reaction mixture into water, and extracting the mixture with an organic solvent, or collecting a deposited precipitate by filtration.
  • the isolated Compound (20) may be further purified by recrystallization, chromatography, or the like.
  • the compounds (3), (4) and (13) are known compounds, or can be produced from known compounds according to known processes (e.g. see Organic Functional Group Preparations, 2nd edition, Vol.l, chapter 12, p.359-376 (Stanley R. Sandler, Wolf Karo.) or Organic Functional Group Preparations, 2nd edition, Vol.l, chapter 14, p.434-465 (Stanley R. Sandler, Wolf Karo.)).
  • the following compound is mentioned:
  • X a represents a nitrogen atom or CR 20ax ,
  • Y and Z represent independently a nitrogen atom or CR 4b , but not Y and Z are CR 4b at the same time,
  • R 1 is a hydrogen atom or C1-C6 alkyl optionally- substituted with one or more halogen atoms
  • R 2 represent a hydrogen atom, C1-C6 alkyl optionally substituted with one or more halogen atoms, C2-C6 cyanoalkyl, C1-C6 hydroxyalkyl, C2-C6 alkoxyalkyl optionally substituted with one or more halogen atoms, C2- C6 alkenyl optionally substituted with one or more halogen atoms, C2-C6 alkynyl optionally substituted with one or more halogen atoms, C3-C6 cycloalkyl optionally substituted with one or more halogen atoms, C1-C6 alkylthio optionally substituted with one or more halogen atoms, C1-C6 alkylsulfinyl optionally substituted with one or more halogen atoms, C1-C6 alkylsulfonyl optionally substituted with one or more halogen atoms, C2-C6 alkylcarbonyl optionally substituted with one or more
  • R 4a , R 4b and R 4c are independently a halogen atom, cyano, nitro, hydroxyl, carboxyl, C1-C6 alkyl optionally substituted with one or more halogen atoms, C1-C6 alkoxy optionally substituted with one or more halogen atoms, C2- C6 cyanoalkyl , C2-C6 alkoxyalkyl optionally substituted with one or more halogen atoms, C2-C6 alkenyl optionally substituted with one or more halogen atoms, C2-C6 alkynyl optionally substituted with one or more halogen atoms, C3- C6 cycloalkyl optionally substituted with one or more halogen atoms, C1-C6 alkylthio optionally substituted with one or more halogen atoms, C1-C6 alkylsulfinyl optionally substituted with one or more halogen atoms, C1-C6 alky
  • R 19ax represent a hydrogen atom; C1-C6 alkyl optionally substituted with one or more halogen atoms; C2- C6 cyanoalkyl; C2-C6 alkoxyalkyl optionally substituted with one or more halogen atoms; C2-C6 alkenyl optionally substituted with one or more halogen atoms; C2-C6 alkynyl optionally substituted with one or more halogen atoms; C3- C6 cycloalkyl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, and (2) C1-C6 alkyl optionally substituted with one or more halogen atoms; phenyl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) C1-C6 alkyl optionally substituted with one or more halogen atoms, (5) C1-C6
  • 5- to 6-membered heteroaryl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) C1-C6 alkyl optionally substituted with one or more halogen atoms, (5) C1-C6 alkoxy optionally substituted with one or more halogen atoms, (6) C1-C6 alkylthio optionally substituted with one or more halogen atoms, (7) C1-C6 alkylsulfinyl optionally substituted with one or more halogen atoms, (8) Cl-C ⁇ alkylsulfonyl optionally substituted with one or more halogen atoms, (9) C1-C6 alkylamino optionally substituted with one or more halogen atoms, (10) C2-C6 dialkylamino optionally substituted with one or more halogen atoms, (11) C2-C6 alkylcarbonyl optionally substituted with
  • R 20ax , R 20ay and R 20az represent a halogen atom; cyano; nitro; thiocyanato; C1-C6 alkyl optionally substituted with one or more halogen atoms; C1-C6 alkoxy optionally substituted with one or more halogen atoms; C2-C6 cyanoalkyloxy; C2-C6 alkoxyalkyloxy optionally substituted with one or more halogen atoms; C2-C6 alkenyloxy optionally substituted with one or more halogen atoms; C2-C6 alkynyloxy optionally substituted with one or more halogen atoms; C1-C6 alkylthio optionally substituted with one or more halogen atoms; C1-C6 alkylsulfinyl optionally substituted with one or more halogen atoms; C1-C6 alkylsulfonyl optionally substituted with one or more halogen atoms;
  • 5- to 6-membered heteroaryl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) C1-C6 alkyl optionally substituted with one or more halogen atoms and (5) C1-C6 alkoxy optionally substituted with one or more halogen atoms; or phenoxy optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) C1-C6 alkyl optionally substituted with one or more halogen atoms and (5) C1-C6 alkoxy optionally substituted with one or more halogen atoms.
  • the compound (10) can be produced, for example, according to the following scheme (1) .
  • Scheme (1)
  • a 34 , L 1 , Q', R 2 , R 3 and R 9a are as defined above .
  • R 1"3 , R 4 and n are as defined above, and L 4 represents a leaving group (e.g. a halogen atom, a methanesulfonyloxy group, a p-toluenesulfonyloxy etc.).
  • L 4 represents a leaving group (e.g. a halogen atom, a methanesulfonyloxy group, a p-toluenesulfonyloxy etc.).
  • the compound (8) can be produced, for example, according to the process shown in the following Scheme (7) .
  • Scheme (7)
  • J is as defined above, R 17 represents a methyl or an ethyl group, LDA represents lithium diisopropylamide, n-BuLi represents normal butyl lithium, and t-BuLi represents tertiary butyl lithium.
  • R 13a , R 14a , X a , Y a , Z a , p, LDA and n-BuLi are as defined above, and L 5 represents a leaving group (e.g. a halogen atom, a methanesulfonyloxy group, a p- toluenesulfonyloxy group, a methylsulfonyl etc.).
  • L 5 represents a leaving group (e.g. a halogen atom, a methanesulfonyloxy group, a p- toluenesulfonyloxy group, a methylsulfonyl etc.).
  • R 14a and p are as defined above, R 18a , R 18b , R 18c and R 18d , each, independently, represent a hydrogen atom, a halogen atom, cyano group, nitro group, C1-C6 alkyl optionally substituted with at least one halogen atom, Cl- C6 alkoxy optionally substituted with at least one halogen atom, C1-C6 alkylthio optionally substituted with at least one halogen atom, C1-C6 alkylsulfinyl optionally substituted with at least one halogen atom, or C1-C6 alkylsulfonyl optionally substituted with at least one halogen atom, can be produced, for example, according to the process shown in the following Scheme (9) .
  • Scheme (9) Scheme (9)
  • R 14a , R 18a , R 18b , R 18c , R 18d , LDA and p are as defined above, and L 6 represents a leaving group (e.g. a halogen atom, a methylsulfonyl etc.).
  • R 18a , R 18b , R 18c , R 18d and R 18e are as defined above .
  • R 14a ⁇ R 17 , R 18a , R 18b , R 18c , R 18d and X 18 are as defined above, and R 20 represents a methyl or an ethyl group.
  • L 2 and J are as defined above, LDA represents lithium diisopropylamide, n-BuLi represents normal butyl lithium, and t-BuLi represents tertiary butyl lithium.
  • R 18a , R 18b , R 18c , R 18d and X 18 are as defined above, and R 14ax , R 14ay and X 14az independently represent a hydrogen atom, a halogen atom, cyano group, C1-C6 alkyl optionally substituted with at least one halogen atom, C1-C6 alkoxy optionally substituted with at least one halogen atom, Cl- C6 alkylthio optionally substituted with at least one halogen atom, C1-C6 alkylsulfinyl optionally substituted with at least one halogen atom, or C1-C6 alkylsulfonyl optionally substituted with at least one halogen atom, can be produced, for example, according to the process shown in the following Scheme (18) .
  • R 18a , R 18b , R 18c , R 18d , X 18 , R 14ax , R 14ay and X 14az are as defined above.
  • X 14az and L 6 are as defined above.
  • R 18a , R 18b , R 18c , R 18d and X 18 are as defined above, £- 4ay - i re p resen ts a hydrogen atom or a halogen atom, R 30 represents C1-C6 alkyl optionally substituted with at least one halogen atom, and r represents an integer of 0 to 2, can be produced, for example, according to the process shown in the following Scheme (21) .
  • R 14ay Horhalo
  • R 18a , R 18b , R 18c , R 18d , X 18 , R 14 ⁇ "1 , R 30 , r and L 4 are as defined above.
  • Compund 8 Compounds of formula IA wherein R 2 , R 3 , M, R 19a , R 20a ⁇ and X corresponds to a row in Table A, and E substituted with
  • Compund 12 Compounds of formula IA wherein R 2 , R 3 , M, R 19a , R 20ay and X corresponds to a row in Table A, and E substituted with
  • Compund 17 Compounds of formula IA wherein R 2 , R 3 , M, R 19a , R 20a ⁇ and X corresponds to a row in Table A, and E substituted with
  • Compund 18 Compounds of formula IA wherein R 2 , R 3 , M, R 19a , R 20a ⁇ and X corresponds to a row in Table A, and E substituted with
  • Compund 19 Compounds of formula IA wherein R 2 , R 3 , M, R 19a , R 20ay and X corresponds to a row in Table A, and E substituted with
  • R is : Compund 20: Compounds of formula IA wherein R 2 , R 3 , M, R 19a , R 20ay and X corresponds to a row in Table A, and E substituted with
  • Compund 21 Compounds of formula IA wherein R 2 , R 3 , M, R 19a , R 20ay and X corresponds to a row in Table A, and E substituted with
  • Compund 22 Compounds of formula IA wherein R 2 , R 3 , M, R 19a , R 20ay and X corresponds to a row in Table A, and E substituted with
  • Compund 23 Compounds of formula IA wherein R 2 , R 3 , M, R 19a , R 2Oay and X corresponds to a row in Table A, and E substituted with
  • Compund 24 Compounds of formula IA wherein R 2 , R 3 , M, R 19a , R 20ay and X corresponds to a row in Table A, and E substituted with (R 4 )n is:
  • Compund 71 Compounds of formula 2A wherein R 2 , R 3 , M and R 20ay corresponds to a row in Table B, and E substituted with
  • R 4 is Compund 75: Compounds of formula 2A wherein R 2 , R 3 , M and R 20ay corresponds to a row in Table B, and E substituted with
  • Compund 81 Compounds of formula 2A wherein R ⁇ , R J , M and R ⁇ corresponds to a row in Table B, and E substituted with
  • Compund 82 Compounds of formula 2A wherein R z , R J , M and R ⁇ corresponds to a row in Table B, and E substituted with
  • Compund 83 Compounds of formula 2A wherein R ⁇ , R J , M and R ⁇ corresponds to a row in Table B, and E substituted with
  • Compund 84 Compounds of formula 2A wherein R 2 , R 3 , M and R 20ay corresponds to a row in Table B, and E substituted with
  • Compund 85 Compounds of formula 2A wherein R 2 , R 3 , M and R 203 ⁇ corresponds to a row in Table B, and E substituted with
  • Compund 86 Compounds of formula 2A wherein R 2 , R 3 , M and R 20ay corresponds to a row in Table B, and E substituted with
  • Compund 87 Compounds of formula 2A wherein R 2 , R 3 , M and R 20ay corresponds to a row in Table B, and E substituted with ( R' is :
  • Compund 129 Compounds of formula 3A wherein R , R 3 , M and R corresponds to a row in Table C, and E substituted with
  • Compund 135 Compounds of formula 3A wherein R 2 , R 3 , M and R 20ax corresponds to a row in Table C, and E substituted with
  • Compund 136 Compounds of formula 3A wherein R 2 , R 3 , M and R 20ax corresponds to a row in Table C, and E substituted with
  • Compund 137 Compounds of formula 3A wherein R 2 , R 3 , M and R 20ax corresponds to a row in Table C, and E substituted with
  • Compund 139 Compounds of formula 3A wherein R 2 , R 3 , M and R 20ax corresponds to a row in Table C, and E substituted with
  • Compund 141 Compounds of formula 3A wherein R 2 , R 3 , M and R 20ax corresponds to a row in Table C, and E substituted with (R 4 is :

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Abstract

A hydrazide compound represented by the formula (I), an N-oxide thereof or suitable salt thereof: has excellent pesticidal activity.

Description

DESCRIPTION
HETEROCYCLIC HYDRAZIDE COMPOUND AND
PESTICIDAL USE OF THE SAME
Technical Field
The present invention relates to a hydrazide compound and pesticidal use of the same.
Background Art
WO 2002/ 070483 discloses several 5- and 6-membered heteroaromatic diamide compounds activity. Furthermore, in WO 2007/020050 is heterobicylic diamide compounds described and their use of for controlling harmful pests in agriculture.
Disclosure of the Invention
The present invention is intended to provide a compound having excellent efficacy of controlling pests. The present inventors have intensively studied in order to find out a compound having excellent efficacy of controlling pests and, as a result, found out that a hydrazide compound represented by the following formula (1) has excellent controlling efficacy. Thus, the present invention has been completed. According to the present invention, there is provided:
A hydrazide compound represented by the formula (I) (hereinafter referred to as the present compound) , an N- oxide thereof or suitable salt thereof:
Figure imgf000003_0001
wherein,
A1 and A2 independently represent an oxygen atom or a sulfur atom;
E represents, together with the two contiguous linking carbon atoms, a 5- or 6-membered heteroaromatic ring system or a 8, 9 or 10-membered fused heterobicyclic ring system
R1 represents a hydrogen atom, C1-C6 alkyl optionally substituted with one or more halogen atoms, C2-C6 cyanoalkyl, C1-C6 hydroxyalkyl, C2-C6 alkoxyalkyl optionally substituted with one or more halogen atoms, C2- C6 alkenyl optionally substituted with one or more halogen atoms, C2-C6 alkynyl optionally substituted with one or more halogen atoms, C3-C6 cycloalkyl optionally substituted with one or more halogen atoms, C1-C6 alkylthio optionally substituted with one or more halogen atoms, C1-C6 alkylsulfinyl optionally substituted with one or more halogen atoms, Cl-Cβ alkylsulfonyl optionally substituted with one or more halogen atoms, C2-C6 alkylcarbonyl optionally substituted with one or more halogen atoms, C2- C6 alkoxycarbonyl, C2-C6 alkylaminocarbonyl, C3-C8 dialkylaminocarbonyl, C4-C6 cycloalkylaminocarbonyl, or C3- C6 trialkylsilyl; or represents phenyl, C7-C9 phenylalkyl or phenylcarbonyl : each said phenyl ring optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) hydroxyl, (5) carboxyl, (6) C1-C6 alkyl optionally substituted with one or more halogen atoms, (7) C1-C6 hydroxyalkyl, (8) C1-C6 alkoxy optionally substituted with one or more halogen atoms, (9) C2-C6 cyanoalkyl, (10) C2-C6 alkoxyalkyl optionally substituted with one or more halogen atoms, (11) C2-C6 alkenyl optionally substituted with one or more halogen atoms, (12) C2-C6 alkynyl optionally substituted with one or more halogen atoms, (13) C3-C6 cycloalkyl optionally substituted with one or more halogen atoms, (14) C1-C6 alkylthio optionally substituted with one or more halogen atoms, (15) Cl-Cβ alkylsulfinyl optionally substituted with one or more halogen atoms, (16) C1-C6 alkylsulfonyl optionally substituted with one or more halogen atoms, (17) Cl-Cβ alkylamino, (18) C2-C8 dialkylamino, (19) C3-C6 cycloalkylamino, (20) C2-C6 alkylcarbonyl, (21) C2-C6 alkoxycarbonyl, (22) C2-C6 alkylaminocarbonyl, (23) C3-C8 dialkylaminocarbonyl, (24) C4-C6 cycloalkylaminocarbonyl and (25) C3-C6 trialkylsilyl,
R2 and R3 independently represent a hydrogen atom, Cl- C6 alkyl optionally substituted with one or more halogen atoms, C2-C6 cyanoalkyl, C1-C6 hydroxyalkyl, C2-C6 alkoxyalkyl optionally substituted with one or more halogen atoms, C2-C6 alkenyl optionally substituted with one or more halogen atoms, C2-C6 alkynyl optionally substituted with one or more halogen atoms, C3-C6 cycloalkyl optionally substituted with one or more halogen atoms, C1-C6 alkylthio optionally substituted with one or more halogen atoms, Cl- Cβ alkylsulfinyl optionally substituted with one or more halogen atoms, C1-C6 alkylsulfonyl optionally substituted with one or more halogen atoms, C2-C6 alkylcarbonyl optionally substituted with one or more halogen atoms, C2- C6 alkoxycarbonyl, C2-C6 alkylaminocarbonyl, C3-C8 dialkylaminocarbonyl, C4-C6 cycloalkylaminocarbonyl, or C3- C6 trialkylsilyl; or represents phenyl, C7-C9 phenylalkyl or phenylcarbonyl : each said phenyl ring optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) hydroxyl, (5) carboxyl, (6) C1-C6 alkyl optionally substituted with one or more halogen atoms, (7) C1-C6 hydroxyalkyl, (8) C1-C6 alkoxy optionally substituted with one or more halogen atoms, (9) C2-C6 cyanoalkyl, (10) C2-C6 alkoxyalkyl optionally substituted with one or more halogen atoms, (11) C2-C6 alkenyl optionally substituted with one or more halogen atoms, (12) C2-C6 alkynyl optionally substituted with one or more halogen atoms, (13) C3-C6 cycloalkyl optionally substituted with one or more halogen atoms, (14) C1-C6 alkylthio optionally substituted with one or more halogen atoms, (15) C1-C6 alkylsulfinyl optionally substituted with one or more halogen atoms, (16) C1-C6 alkylsulfonyl optionally- substituted with one or more halogen atoms, (17) C1-C6 alkylamino, (18) C2-C8 dialkylamino, (19) C3-C6 cycloalkylamino, (20) C2-C6 alkylcarbonyl, (21) C2-C6 alkoxycarbonyl, (22) C2-C6 alkylaminocarbonyl, (23) C3-C8 dialkylaminocarbonyl, (24) C4-C6 cycloalkylaminocarbonyl and (25) C3-C6 trialkylsilyl; or
R2 and R3 are taken together with the two nitrogen atoms to which they are attached to form a 5 to 8 membered ring containing two nitrogen atoms, one or more CH2 or C(=0), and optionally one or two ring members selected from the group consisting of (1) an oxygen atom, (2) a sulfur atom, (3) S(=0), (4) S(=0)2 and (4) NRa (wherein Ra represents C1-C6 alkyl optionally substituted with one or more halogen atoms, C2-C6 alkoxycarbonyl optionally substituted with one or more halogen atoms, or a phenyl optionally substituted with one or more independent substituents from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) C1-C6 alkyl optionally substituted with one or more halogen atoms, (5) C1-C6 alkoxy optionally substituted with one or more halogen atoms, (6) C1-C6 alkylthio optionally substituted with one or more halogen atoms, (7) C1-C6 alkylsulfinyl optionally substituted with one or more halogen atoms, (8) C1-C6 alkylsulfonyl optionally substituted with one or more halogen atoms, (9) C1-C6 alkylamino optionally substituted with one or more halogen atoms, (10) C2-C6 dialkylamino optionally substituted with one or more halogen atoms, (11) C2-C6 alkylcarbonyl optionally substituted with one or more halogen atoms, (12) C2-C6 alkoxycarbonyl optionally substituted with one or more halogen atoms, (13) C2-C6 alkylaminocarbonyl optionally substituted with one or more halogen atoms and (14) C3-C6 dialkylaminocarbonyl optionally substituted with one or more halogen atoms); and wherein the ring at the carbon atoms is optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) C1-C6 alkyl optionally substituted with one or more halogen atoms, and (3) C2-C6 alkoxycarbonyl optionally substituted with one or more halogen atoms;
R4 represents a halogen atom, cyano, nitro, hydroxyl, carboxyl, C1-C6 alkyl optionally substituted with one or more halogen atoms, Cl-Cβ alkoxy optionally substituted with one or more halogen atoms, C2-C6 cyanoalkyl, C2-C6 alkoxyalkyl optionally substituted with one or more halogen atoms, C2-C6 alkenyl optionally substituted with one or more halogen atoms, C2-C6 alkynyl optionally substituted with one or more halogen atoms, C3-C6 cycloalkyl optionally substituted with one or more halogen atoms, C1-C6 alkylthio optionally substituted with one or more halogen atoms, Cl- Cβ alkylsulfinyl optionally substituted with one or more halogen atoms, Cl-Cβ alkylsulfonyl optionally substituted with one or more halogen atoms, Cl-Cβ alkylamino, C2-C8 dialkylamino, C3-C6 cycloalkylamino, C2-C6 alkylcarbonyl optionally substituted with one or more halogen atoms, C2- C6 alkoxycarbonyl, C2-C6 alkylaminocarbonyl, C3-C8 dialkylaminocarbonyl, or C3-C6 trialkylsilyl; or represents a phenyl, benzyl, phenoxy, or a 5- or 6- membered heteroaromatic ring, each ring optionally substituted with one or more substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) hydroxyl, (5) carboxyl, (6) C1-C6 alkyl optionally substituted with one or more halogen atoms, (7) C1-C6 hydroxyalkyl, (8) C1-C6 alkoxy optionally substituted with one or more halogen atoms, (9) C2-C6 cyanoalkyl, (10) C2-C6 alkoxyalkyl optionally substituted with one or more halogen atoms, (11) C2-C6 alkenyl optionally substituted with one or more halogen atoms, (12) C2-C6 alkynyl optionally substituted with one or more halogen atoms, (13) C3-C6 cycloalkyl optionally substituted with one or more halogen atoms, (14) Cl-Cβ alkylthio optionally substituted with one or more halogen atoms, (15) C1-C6 alkylsulfinyl optionally substituted with one or more halogen atoms, (16) C1-C6 alkylsulfonyl optionally substituted with one or more halogen atoms, (17) C1-C6 alkylamino, (18) C2-C8 dialkylamino, (19) C3-C6 cycloalkylamino, (20) C2-C6 alkylcarbonyl, (21) C2-C6 alkoxycarbonyl, (22) C2-C6 alkylaminocarbonyl, (23) C3-C8 dialkylaminocarbonyl, (24)
C4-C6 cycloalkylaminocarbonyl and (25) C3-C6 trialkylsilyl,
n represents an integer of 0 to 3 (provided that, when n is an integer of 2 or more, R4's may be the same or different) ; Q represents Ql , Q2 , Q3 , Q4 , Q5 or Q6 :
Ql : C(=A31)— R6
Q2 : C(=A32)— OR7
Q3 : C(=A33)— SR8
Q4 : CC=A34)- NR9R10
Q5 : S(O)-R11
Q6 : S(O)^-NR12R13 ,
A31, A32, A33 and A34 represent an oxygen atom, or a sulfur atom; m represents an integer of 0 to 2
R6 represents a hydrogen atom; C2-C6 alkenyl optionally substituted with one or more halogen atoms; C2- C6 alkynyl optionally substituted with one or more halogen atoms; C1-C6 alkyl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) C1-C6 alkoxy optionally substituted with one or more halogen atoms, (3) C1-C6 alkylthio optionally substituted with one or more halogen atoms, (4) C1-C6 alkylsulfinyl optionally substituted with one or more halogen atoms, (5) C1-C6 alkylsulfonyl optionally substituted with one or more halogen atoms, (6) C2-C6 dialkylamino optionally substituted with one or more halogen atoms, and (7) C3-C6 cycloalkyl optionally substituted with one or more halogen atoms; C3-C6 cycloalkyl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, and (2) C1-C6 alkyl optionally substituted with one or more halogen atoms; phenyl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) Cl-Cβ alkyl optionally substituted with one or more halogen atoms, (5) C1-C6 alkoxy optionally substituted with one or more halogen atoms, (6) C1-C6 alkylthio optionally substituted with one or more halogen atoms, (7) C1-C6 alkylsulfinyl optionally substituted with one or more halogen atoms, (8) C1-C6 alkylsulfonyl optionally substituted with one or more halogen atoms, (9) C1-C6 alkylamino optionally substituted with one or more halogen atoms, (10) C2-C6 dialkylamino optionally substituted with one or more halogen atoms, (11) C2-C6 alkylcarbonyl optionally substituted with one or more halogen atoms, (12) C2-C6 alkoxycarbonyl optionally substituted with one or more halogen atoms, (13) C2-C6 alkylaminocarbonyl optionally substituted with one or more halogen atoms and (14) C3-C6 dialkylaminocarbonyl optionally substituted with one or more halogen atoms; naphthyl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) C1-C6 alkyl optionally substituted with one or more halogen atoms and (5) C1-C6 alkoxy optionally substituted with one or more halogen atoms; 5- to 6-membered heteroaryl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) C1-C6 alkyl optionally substituted with one or more halogen atoms and (5) Cl-Cβ alkoxy optionally substituted with one or more halogen atoms; 3- to 8-membered non-aromatic heterocyclic ring optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, and (2) C1-C6 alkyl optionally substituted with one or more halogen atoms; C7-C9 phenylalkyl or C7-C9 phenoxyalkyl : each said phenyl ring optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) C1-C6 alkyl optionally substituted with one or more halogen atoms and (5) C1-C6 alkoxy optionally substituted with one or more halogen atoms,
R7 and R8 represent C1-C6 alkyl optionally substituted with one or more halogen atoms; C2-C6 alkoxyalkyl optionally substituted with one or more halogen atoms; C2- C6 alkenyl optionally substituted with one or more halogen atoms; C2-C6 alkynyl optionally substituted with one or more halogen atoms; C3-C6 cycloalkyl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, and (2) C1-C6 alkyl optionally substituted with one or more halogen atoms; phenyl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) C1-C6 alkyl optionally substituted with one or more halogen atoms, (5) C1-C6 alkoxy optionally substituted with one or more halogen atoms, (6) C1-C6 alkylthio optionally substituted with one or more halogen atoms, (7) C1-C6 alkylsulfinyl optionally substituted with one or more halogen atoms, (8) C1-C6 alkylsulfonyl optionally substituted with one or more halogen atoms, (9) C1-C6 alkylamino optionally substituted with one or more halogen atoms, (10) C2-C6 dialkylamino optionally substituted with one or more halogen atoms, (11) C2-C6 alkylcarbonyl optionally substituted with one or more halogen atoms, (12) C2-C6 alkoxycarbonyl optionally substituted with one or more halogen atoms, (13) C2-C6 alkylaminocarbonyl optionally substituted with one or more halogen atoms and (14) C3-C6 dialkylaminocarbonyl optionally substituted with one or more halogen atoms; 5- to 6-membered heteroaryl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) C1-C6 alkyl optionally substituted with one or more halogen atoms and (5) C1-C6 alkoxy optionally substituted with one or more halogen atoms; or C7-C9 phenylalkyl whose phenyl ring moiety optionally is substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) C1-C6 alkyl optionally substituted with one or more halogen atoms and (5) C1-C6 alkoxy optionally substituted with one or more halogen atoms,
R9 and R10 independently represent a hydrogen atom; Cl- C6 alkyl optionally substituted with one or more halogen atoms; C2-C6 alkoxyalkyl optionally substituted with one or more halogen atoms; C2-C6 alkenyl optionally substituted with one or more halogen atoms; C2-C6 alkynyl optionally substituted with one or more halogen atoms; C3-C6 cycloalkyl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, and (2) C1-C6 alkyl optionally substituted with one or more halogen atoms; phenyl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) C1-C6 alkyl optionally substituted with one or more halogen atoms, (5) C1-C6 alkoxy optionally substituted with one or more halogen atoms, (6) C1-C6 alkylthio optionally substituted with one or more halogen atoms, (7) C1-C6 alkylsulfinyl optionally substituted with one or more halogen atoms, (8) C1-C6 alkylsulfonyl optionally substituted with one or more halogen atoms, (9) C1-C6 alkylamino optionally substituted with one or more halogen atoms, (10) C2-C6 dialkylamino optionally substituted with one or more halogen atoms, (11) C2-C6 alkylcarbonyl optionally substituted with one or more halogen atoms, (12) C2-C6 alkoxycarbonyl optionally substituted with one or more halogen atoms, (13) C2-C6 alkylaminocarbonyl optionally substituted with one or more halogen atoms and (14) C3-C6 dialkylaminocarbonyl optionally substituted with one or more halogen atoms; 5- to 6-membered heteroaryl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) C1-C6 alkyl optionally substituted with one or more halogen atoms and (5) C1-C6 alkoxy optionally substituted with one or more halogen atoms; or C7-C9 phenylalkyl whose phenyl ring moiety optionally is substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) C1-C6 alkyl optionally substituted with one or more halogen atoms and (5) C1-C6 alkoxy optionally substituted with one or more halogen atoms,
R11 represents C1-C6 alkyl optionally substituted with one or more halogen atoms; C3-C6 cycloalkyl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, and (2) C1-C6 alkyl optionally substituted with one or more halogen atoms; or a phenyl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) C1-C6 alkyl optionally substituted with one or more halogen atoms and (5) Cl-Cβ alkoxy optionally substituted with one or more halogen atoms; 5- to 6-membered heteroaryl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) C1-C6 alkyl optionally substituted with one or more halogen atoms and (5) Cl-Cβ alkoxy optionally substituted with one or more halogen atoms; or 3- to 8-membered non-aromatic heterocyclic ring optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, and (2) Cl-Cβ alkyl optionally substituted with one or more halogen atoms,
R12 and R13 independently represent C1-C6 alkyl optionally substituted with one or more halogen atoms; C3- C6 cycloalkyl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, and (2) C1-C6 alkyl optionally substituted with one or more halogen atoms; or phenyl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) C1-C6 alkyl optionally substituted with one or more halogen atoms and (5) C1-C6 alkoxy optionally substituted with one or more halogen atoms;
J represents Jl or J2 :
Figure imgf000017_0001
Xa, Ya, Za, Xb, Yb and Zb independently represent CH or a nitrogen atom;
R19a and R19b represent a hydrogen atom; C1-C6 alkyl optionally substituted with one or more halogen atoms; C2- C6 cyanoalkyl, C2-C6 alkoxyalkyl optionally substituted with one or more halogen atoms; C2-C6 alkenyl optionally substituted with one or more halogen atoms; C2-C6 alkynyl optionally substituted with one or more halogen atoms; C3- C6 cycloalkyl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, and (2) C1-C6 alkyl optionally substituted with one or more halogen atoms; phenyl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) C1-C6 alkyl optionally substituted with one or more halogen atoms, (5) C1-C6 alkoxy optionally substituted with one or more halogen atoms, (6) C1-C6 alkylthio optionally substituted with one or more halogen atoms, (7) C1-C6 alkylsulfinyl optionally substituted with one or more halogen atoms, (8) C1-C6 alkylsulfonyl optionally substituted with one or more halogen atoms, (9) C1-C6 alkylamino optionally substituted with one or more halogen atoms, (10) C2-C6 dialkylamino optionally substituted with one or more halogen atoms, (11) C2-C6 alkylcarbonyl optionally substituted with one or more halogen atoms, (12) C2-C6 alkoxycarbonyl optionally substituted with one or more halogen atoms, (13) C2-C6 alkylaminocarbonyl optionally substituted with one or more halogen atoms and (14) C3-C6 dialkylaminocarbonyl optionally substituted with one or more halogen atoms; 5- to 6-membered heteroaryl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) Cl-Cβ alkyl optionally substituted with one or more halogen atoms, (5) C1-C6 alkoxy optionally substituted with one or more halogen atoms, (6) C1-C6 alkylthio optionally substituted with one or more halogen atoms, (7) C1-C6 alkylsulfinyl optionally substituted with one or more halogen atoms, (8) C1-C6 alkylsulfonyl optionally substituted with one or more halogen atoms, (9) C1-C6 alkylamino optionally substituted with one or more halogen atoms, (10) C2-C6 dialkylamino optionally substituted with one or more halogen atoms, (11) C2-C6 alkylcarbonyl optionally substituted with one or more halogen atoms, (12) C2-C6 alkoxycarbonyl optionally substituted with one or more halogen atoms, (13) C2-C6 alkylaminocarbonyl optionally substituted with one or more halogen atoms and
(14) C3-C6 dialkylaminocarbonyl optionally substituted with one or more halogen atoms; C7-C9 phenylalkyl whose phenyl ring is optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) C1-C6 alkyl optionally substituted with one or more halogen atoms, (5) C1-C6 alkoxy optionally substituted with one or more halogen atoms, (6) C1-C6 alkylthio optionally substituted with one or more halogen atoms, (7) C1-C6 alkylsulfinyl optionally substituted with one or more halogen atoms, (8) C1-C6 alkylsulfonyl optionally substituted with one or more halogen atoms, (9) C1-C6 alkylamino optionally substituted with one or more halogen atoms, (10) C2-C6 dialkylamino optionally substituted with one or more halogen atoms, (11) C2-C6 alkylcarbonyl optionally substituted with one or more halogen atoms, (12) C2-C6 alkoxycarbonyl optionally substituted with one or more halogen atoms, (13) C2-C6 alkylaminocarbonyl optionally substituted with one or more halogen atoms and (14) C3-C6 dialkylaminocarbonyl optionally substituted with one or more halogen atoms; or C7-C9 pyridinylalkyl whose pyridine ring is optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) C1-C6 alkyl optionally substituted with one or more halogen atoms, (5) C1-C6 alkoxy optionally substituted with one or more halogen atoms, (6) C1-C6 alkylthio optionally substituted with one or more halogen atoms, (7) C1-C6 alkylsulfinyl optionally substituted with one or more halogen atoms, (8) C1-C6 alkylsulfonyl optionally substituted with one or more halogen atoms, (9) C1-C6 alkylamino optionally substituted with one or more halogen atoms, (10) C2-C6 dialkylamino optionally substituted with one or more halogen atoms, (11) C2-C6 alkylcarbonyl optionally substituted with one or more halogen atoms, (12) C2-C6 alkoxycarbonyl optionally substituted with one or more halogen atoms, (13) C2-C6 alkylaminocarbonyl optionally substituted with one or more halogen atoms and (14) C3-C6 dialkylaminocarbonyl optionally substituted with one or more halogen atoms,
R20a and R2Ob represent a halogen atom; cyano; nitro; thiocyanato; C1-C6 alkyl optionally substituted with one or more halogen atoms; C1-C6 alkoxy optionally substituted with one or more halogen atoms; C2-C6 cyanoalkyloxy; C2-C6 alkoxyalkyloxy optionally substituted with one or more halogen atoms; C2-C6 alkenyloxy optionally substituted with one or more halogen atoms; C2-C6 alkynyloxy optionally substituted with one or more halogen atoms; C1-C6 alkylthio optionally substituted with one or more halogen atoms; Cl- C6 alkylsulfinyl optionally substituted with one or more halogen atoms; C1-C6 alkylsulfonyl optionally substituted with one or more halogen atoms; phenyl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) C1-C6 alkyl optionally substituted with one or more halogen atoms and (5) C1-C6 alkoxy optionally substituted with one or more halogen atoms; 5- to 6-membered heteroaryl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) C1-C6 alkyl optionally substituted with one or more halogen atoms and (5) C1-C6 alkoxy optionally substituted with one or more halogen atoms; or phenoxy optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) C1-C6 alkyl optionally substituted with one or more halogen atoms and (5) C1-C6 alkoxy optionally substituted with one or more halogen atoms,
p represents an integer of 0 to 3 (provided that, when p is an integer of 2 or 3, two or more R20a's may be the same or different) ;
q represents an integer of 0 to 3 (provided that, when q is an integer of 2 or 3, two or more R20b's may be the same or different) .
Furthermore this invention also contains a method of controlling an invertebrate pest applying the present compound, an N-oxide thereof or an agricultural suitable salt thereof by contacting directly to a pest, or to a place where a pest inhabits. With includes the use of the present compound, an N-oxide thereof or an agricultural suitable salt thereof as active ingredient in a pesticidal composition.
A composition comprising of the present compound, an ΪV-oxide thereof or an agricultural suitable salt thereof and at least one additional component selected from the group of surfactants, solid diluents and liquid diluents. This invention also includes a method for controlling an invertebrate pest by using the present compound, an N-oxide thereof or an agricultural suitable salt thereof as active ingredient in a pesticidal composition and a biological active amount of at least one additional compound or agent. The invention also pertains the use of the present compound, an N-oxide thereof or an agricultural suitable salt thereof for manufacturing a pesticidal preparation.
Best Mode for Carrying Out the Invention
The compounds of this invention include every possible sterioisomer in terms of enantiomers and diastereomers that can be formed from different configuration at centers of asymmetry and different double bond configuration according to well-accepted definition of configuration isomers (Eliel, Ernest L., Wilien, Samuel H., Stereochemistry of Organic Compounds, John Wiley & Son,
1994) . The compounds of the invention can be present as a mixture of the above-mentioned isomers, as a single diastereomer or in an optically enriched form as active ingredients. Furthermore, the compounds of formula I of this invention can be present as an N-oxide thereof or an agricultural suitable salt thereof. All available nitrogen atoms whose lone pairs are not part of an aromatic molecular π-orbital according to Huckel's rule can be oxidized at their lone pairs to form N-oxides by using commonly known methods. Agricultural suitable salts of the compounds of this invention can be formed by addition of an inorganic or organic acid to the compound like for example hydrochloric, hydrobromic, sulfuric, nitric and phosphoric acid as well as acetic, propionic, butyric, oxalic, malonic, tartaric, lactic, maleic, fumaric, citric, p- toluenesulfonic and salicylic acid. In case where compounds contain acidic moieties like carboxyl, sulfonyl or phenol, salts can be formed by addition of an inorganic or organic base like e.g. the hydroxides and carbonates of lithium, sodium, potassium, magnesium, calcium and barium or amines like ammonia, pyridine or triethylamine . The term 'aromatic' and Λheteroaromatic' indicates that the carbocyclic or heterocyclic ring system is fully unsaturated with a planar ring system allowing the ring systems p-orbitals and optionally lone pair orbitals of heteroatoms, which are perpendicular to the ring plane to overlap to form a π-molecular orbital with (4n+2) π- electrons according to Htickel's rule (n is 0 or a positive integer) . The term 'non-aromatic' or λnon- aromatic heterocyclic ring system' refers to a ring system, which is fully or partial saturated or which is fully unsaturated but does not fulfill the requirements of Huckel's rule as mentioned above. The term 'hetero' in 'heteroaromatic' , 'heterobicyclic' and 'non-aromatic heterocyclic ring' denotes a ring system that contains at least one or more atom different from carbon, selected from the group of oxygen, nitrogen and sulfur. The heterocyclic ring system can be attached at any available carbon or nitrogen atom by replacement of hydrogen.
Hereinafter, the examples of the "substituents" are illustrated.
Examples of the 5- or 6-membered heteroaromatic ring system substitutede with (R4) n include E-I to E-39 shown below. The heteroaromatic ring systems E-I to E-39 are attached with their upper right bond of an available carbon atom to the nitrogen atom of the -NR1 (C=A1) J moiety. The hydrazide moiety - (C=A2) NR2NR3Q is attached with the -(C=A2) carbon atom to an available carbon atom at the lower right bond of the exemplified ring systems E-I to E-39.
Figure imgf000026_0001
Figure imgf000027_0001
E-1 E-2 E-3 E-4 E-5
Figure imgf000027_0002
E-X8 <R4)"-l EX-9 <R4)»πζ E-10 °2V:5CS*.
Figure imgf000027_0003
Figure imgf000027_0004
Examples of the 8, 9 or 10-membered fused heterobicyclic ring system substituted with (R4) n include E-40 to E-109 shown below. Substitution of said heterobicyclic ring systems with substituents R4 is possible by substitution of carbon and nitrogen H-atoms on the aromatic ring systems as well as on non-aromatic linking moieties (E-97-101, E-103, E-105, E-107-109) . The heteroaromatic ring systems E-40 to E-109 are attached with their upper right bond of an available carbon atom to the nitrogen atom of the -NR1 (C=A1) J moiety. The hydrazide moiety -(C=A2JNR2NR3Q is attached with the -(C=A2) carbon atom to an available carbon atom at the lower right bond of the exemplified ring systems E-40 to E-109.
Figure imgf000029_0001
E-40 E-41 E-42 E-43 E-44
Figure imgf000029_0002
E-45 E-46 E-47 E-48 E^9
Figure imgf000029_0003
E-50 E-51 E-52 E-53 E-54
Figure imgf000029_0004
E-55 E-56 E-57 E-58 E-59
Figure imgf000029_0005
E-60 E-61 E-62 E-63 E-64
Figure imgf000029_0006
E-65 E-66 E-67 E-68 E-69
Figure imgf000029_0007
E-70 E-71 E-72 E-73 E-74
Figure imgf000030_0001
- E-90 ,,P E-91 E-92 E-93 E-94
Figure imgf000030_0002
E-95 E-96 E-97 E-98 E-99
Figure imgf000030_0003
E-100 E-101 E-102 E-103 E-104
Figure imgf000030_0004
E-105 E-106 E-107 E-108 E-109 Preferred ring systems include E-2, E-4, E-I, E-12, E-13, E-22, E-40 and E47; most preferred E-2 and E-4.
Examples of a halogen atom include a fluorine atom, a chlorine atom, a bromine atom and an iodine atom.
Examples of C1-C6 alkyl optionally substituted with one or more halogen atoms include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl and hexyl as well as fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, 2, 2, 2-trifluoroethyl, 1,1,2,2- tetrafluoroethyl and pentafluoroethyl .
Examples of C1-C6 alkyl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) C1-C6 alkoxy optionally substituted with one or more halogen atoms, (3) C1-C6 alkylthio optionally substituted with one or more halogen atoms, (4) C1-C6 alkylsulfinyl optionally substituted with one or more halogen atoms, (5) C1-C6 alkylsulfonyl optionally substituted with one or more halogen atoms, (6) C2-C6 dialkylamino optionally substituted with one or more halogen atoms, and (7) C3-C6 cycloalkyl optionally substituted with one or more halogen atoms include methyl, trifluoromethyl, trichloromethyl, chloromethyl, dichloromethyl, fluoromethyl, difluoromethyl, methoxymethyl, ethoxymethyl, methylthiomethyl, ethylthiomethyl, methylsulfinylmethyl, methylsulfonylmethyl, dimethylaminomethyl, cyclopropylmethyl, cyclopentylmethyl, cyclohexylmethyl, ethyl, pentafluoroethyl, propyl, isopropyl, butyl, isobutyl , sec-butyl, tert-butyl, pentyl and hexyl .
Examples of C2-C6 cyanoalkyl include cyanomethyl and 2-cyanoethyl .
Examples of C2-C6 cyanoalkoxy include cyanomethoxy and 2-cyanoethoxy .
Examples of Cl-Cβ hydroxyalky include hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, 1-hydroxypropyl, 2- hydroxypropyl, 3-hydroxypropyl and 2-hydroxy-isopropyl .
Examples of C1-C6 alkoxy optionally substituted with one or more halogen atoms include methoxy, trifluoromethoxy, ethoxy, 2, 2, 2-trifluoroethoxy, propyloxy, isopropyloxy, butoxy, isobutyloxy, sec-butoxy, tert-butoxy, pentyloxy and hexyloxy .
Examples of C2-C6 alkoxyalkyl optionally substituted with one or more halogen atoms include methoxymethyl, ethoxymethyl, 2-methoxyethyl, 2-ethoxyethyl and 2- isopropyloxyethyl .
Examples of C2-C6 alkoxyalkyloxy optionally substituted with one or more halogen atoms include 2- (methoxy) ethoxy .
Examples of C2-C6 alkenyl optionally substituted with one or more halogen atoms include 2-propenyl, 3-chloro-2- propenyl, 2-chloro-2-propenyl, 3, 3-dichloro-2-propenyl, 2- butenyl, 3-butenyl, 2-methyl-2-propenyl, 3-methyl-2-butenyl, 2-pentenyl and 2-hexenyl as well as polyenes like 1,3- pentadienyl and 2, 4-hexadienyl and all possible diastereomers .
Examples of C2-C6 alkenyloxy optionally substituted with one or more halogen atoms include 2-propenyloxy, 3,3- dichloro-2-propenoxy and 2-methyl-2-propenyloxy .
Examples of C2-C6 alkynyl optionally substituted with one or more halogen atoms include 2-propynyl, 3-chloro-2- propynyl, 3-bromo-2-propynyl, 2-butynyl and 3-butynyl as well as polyynes like 2, 5-hexadiynyl .
Examples of C2-C6 alkynyloxy optionally substituted with one or more halogen atoms include 2-propynyloxy, 3- chloro-2-propynyloxy and 2-butynyloxy .
Examples of Cl-Cβ alkylthio optionally substituted with one or more halogen atoms include methylthio, trifluoromethylthio, ethylthio, propylthio, isopropylthio, butylthio, isobutylthio, sec-butylthio, tert-butylthio, pentylthio and hexylthio.
Examples of C1-C6 alkylsulfinyl optionally substituted with one or more halogen atoms include methylsulfinyl, trifluoromethylsulfinyl, ethylsulfinyl, propylsulfinyl, isopropylsulfinyl, butylsulfinyl, isobutylsulfinyl, sec-butylsulfinyl, tert-butylsulfinyl, pentylsulfinyl and hexylsulfinyl . The definition includes both sulfoxide enantiomers .
Examples of C1-C6 alkylsulfonyl optionally substituted with one or more halogen atoms include methylsulfonyl, trifluoromethylsulfonyl, ethylsulfonyl, propylsulfonyl, isopropylsulfonyl, butylsulfonyl, isobutylsulfonyl, sec-butylsulfonyl, tert-butylsulfonyl, pentylsulfonyl and hexylsulfonyl .
Examples of C1-C6 alkylamino include methylamino, ethylamino, n-propylamino, isopropylamino, n-butylamino, sec-butylamino, isobutylamino and tert-butylamino .
Examples of C1-C6 alkylamino optionally substituted with one or more halogen atoms alkylamino include methylamino, ethylamino, n-propylamino, isopropylamino, n- butylamino, sec-butylamino, isobutylamino, tert-butylamino, 2-fluoroethyl amino, 2, 2, 2-trifluoroethyl amino, 2,2,3,3,3- pentafluoropropyl amino and 2, 2, 3, 3, 4 , 4 , 4-heptafluoroamino.
Examples of C2-C8 dialkylamino include dimethylamino, diethylamino, ethylmethylamino, di-n-propylamino, diisopropylamino and di-n-butylamino.
Examples of C2-C8 dialkylamino optionally substituted with one or more halogen atoms include dimethylamino, diethylamino, ethylmethylamino, bis (2,2,2- trifluoroethyl) amino, di-n-propylamino, diisopropylamino and di-n-butylamino.
Examples of C3-C6 cycloalkylamino include cyclopropyl amino, cyclobutylamino, cyclopentylamino and cyclohexylamino .
Examples of C2-C6 alkylcarbonyl include acetyl, propionyl, isobutyryl and trimethylacetyl . Examples of C2-C6 alkylcarbonyl optionally substituted with one or more halogen atoms include acetyl, trifluoroacetyl, trichloroacetyl, propionyl, pentafluoropropionyl, isobutyryl and trimethylacetyl .
Examples of C2-C6 alkoxycarbonyl include methoxycarbonyl, ethoxycarbonyl, isopropoxycarbonyl and tert-butoxycarbonyl
Examples of C2-C6 alkoxycarbonyl optionally substituted with one or more halogen atoms include methoxycarbonyl, ethoxycarbonyl, 2-fluoroethoxycarbonyl, 2,2, 2-trifluoroethoxycarbonyl, 2,2,2- trichloroethoxycarbonyl, isopropoxycarbonyl and tert- butoxycarbonyl .
Examples of C2-C6 alkylaminocarbonyl includes methylaminocarbonyl, ethylaminocarbonyl, n- propylaminocarbonylcarbonyl, isopropylaminocarbonyl, n- butylaminocarbonyl, see-butylaminocarbonyl, isobutylaminocarbonyl and tert-butylaminocarbonyl . Examples of C2-C6 alkylaminocarbonyl optionally substituted with one or more halogen atoms include methylaminocarbonyl, ethylaminocarbonyl, n- propylaminocarbonyl, isopropylaminocarbonyl, n- butylaminocarbonyl , sec-butylaminocarbonyl , isobutylaminocarbonyl, tert-butylaminocarbonyl, 2- fluoroethylaminocarbonyl, 2,2, 2-trifluoroethylaminocarbonyl, 2,2,3,3, 3-pentafluoropropylcarbonylaminocarbonyl and 2,2,3,3,4,4, 4-heptafluorobutylaminocarbonyl .
Examples of C3-C8 dialkylaminocarbonyl include dimethylaminocarbonyl and diethylaminocarbonyl .
Examples of C4-C6 cycloalkylaminocarbonyl include cyclopropylaminocarbonyl, cyclobutylaminocarbonyl, cyclopentylaminocarbonyl and cyclohexylaminocarbonyl .
Examples of C3-C6 trialkylsilyl include trimthylsilyl, triethylsilyl and tertbutyldimethylsilyl .
Examples of C3-C6 cycloalkyl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, and (2) C1-C6 alkyl optionally substituted with one or more halogen atoms include cyclopropyl, 2-methylcyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl.
Examples of phenyl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) hydroxyl, (5) carboxyl, (6) C1-C6 alkyl optionally substituted with one or more halogen atoms, (7) C1-C6 hydroxyalkyl, (8) C1-C6 alkoxy optionally substituted with one or more halogen atoms, (9) C2-C6 cyanoalkyl optionally substituted with one or more halogen atoms, (10) C2-C6 alkoxyalkyl optionally substituted with one or more halogen atoms, (11) C2-C6 alkenyl optionally substituted with one or more halogen atoms, (12) C2-C6 alkynyl optionally substituted with one or more halogen atoms, (13) C3-C6 cycloalkyl optionally substituted with one or more halogen atoms, (14) C1-C6 alkylthio optionally substituted with one or more halogen atoms, (15) C1-C6 alkylsulfinyl optionally substituted with one or more halogen atoms, (16) C1-C6 alkylsulfonyl optionally substituted with one or more halogen atoms, (17) C1-C6 alkylamino, (18) C2-C8
' dialkylamino, (19) C3-C6 cycloalkylamino, (20) C2-C6 alkylcarbonyl, (21) C2-C6 alkoxycarbonyl, (22) C2-C6 alkylaminocarbonyl, (23) C3-C8 dialkylaminocarbonyl, (24) C4-C6 cycloalkylaminocarbonyl and (25) C3-C6 trialkylsilyl include phenyl, 2-fluorophenyl, 3-fluorophenyl, 4-fluorophenyl, 2- chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2-bromophenyl, 2-iodophenyl, 2, 6-difluorophenyl, 2, 6-dichlorophenyl, 2- chloro-6-fluorophenyl, 2-chloro-4-fluorophenyl, 2- cyanophenyl, 3-cyanophenyl, 4-cyanophenyl, 2-nitrophenyl, 3-nitrophenyl, 4-nitrophenyl, 2-methylphenyl, 3- methylphenyl, 4-methylphenyl, 2-ethylphenyl, 2- isopropylphenyl, 2-tert-butylphenyl, 2- (trifluoromethyl) phenyl, 3- (trifluoromethyl) phenyl, A- (trifluoromethyl) phenyl, 2-methoxyphenyl, 3-methoxyphenyl,
4-methoxyphenyl, 2-ethoxyphenyl, 2- (trifluoromethoxy) phenyl, 2- (methylthio) phenyl, 2- (methylsulfinyl) phenyl and 2- (methylsulfonyl) phenyl .
Examples of benzyl optionally substituted with one or more substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) hydroxyl, (5) carboxyl, (6) C1-C6 alkyl optionally substituted with one or more halogen atoms, (7) C1-C6 hydroxyalkyl, (8) C1-C6 alkoxy optionally substituted with one or more halogen atoms, (9) C2-C6 cyanoalkyl optionally substituted with one or more halogen atoms, (10) C2-C6 alkoxyalkyl optionally substituted with one or more halogen atoms, (11) C2-C6 alkenyl optionally substituted with one or more halogen atoms, (12) C2-C6 alkynyl optionally substituted with one or more halogen atoms, (13) C3-C6 cycloalkyl optionally substituted with one or more halogen atoms, (14) C1-C6 alkylthio optionally substituted with one or more halogen atoms, (15) C1-C6 alkylsulfinyl optionally substituted with one or more halogen atoms, (16) C1-C6 alkylsulfonyl optionally substituted with one or more halogen atoms, (17) C1-C6 alkylamino, (18) C2-C8 dialkylamino, (19) C3-C6 cycloalkylamino, (20) C2-C6 alkylcarbonyl, (21) C2-C6 alkoxycarbonyl, (22) C2-C6 alkylaminocarbonyl, (23) C3-C8 dialkylaminocarbonyl, (24) C4-C6 cycloalkylaminocarbonyl and (25) C3-C6 trialkylsilyl include benzyl, 2-fluorobenzyl, 3-fluorobenzyl, 4-fluorobenzyl, 2- chlorobenzyl, 3-chlorobenzyl, 4-chlorobenzyl, 2-bromobenzyl, 2-iodobenzyl, 2, 6-difluorobenzyl, 2, 6-dichlorobenzyl, 2- chloro-6-fluorobenzyl, 2-chloro-4-fluorobenzyl, 2- cyanobenzyl, 3-cyanobenzyl, 4-cyanobenzyl, 2-nitrobenzyl, 3-nitrobenzyl, 4-nitrobenzyl, 2-methylbenzyl, 3- methylbenzyl, 4-methylbenzyl, 2-ethylbenzyl, 2- isopropylbenzyl, 2-tert-butylbenzyl, 2- (trifluoromethyl) benzyl, 3- (trifluoromethyl) benzyl, 4-
(trifluoromethyl) benzyl, 2-methoxybenzyl, 3-methoxybenzyl, 4-methoxybenzyl, 2-ethoxybenzyl, 2- (trifluoromethoxy) benzyl, 2- (methylthio) benzyl, 2- (methylsulfinyl) benzyl and 2- (methylsulfonyl ) benzyl .
Examples of C7-C9 phenylalkyl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) hydroxyl, (5) carboxyl, (6) C1-C6 alkyl optionally substituted with one or more halogen atoms, (7) C1-C6 hydroxyalkyl, (8) Cl-Cβ alkoxy optionally substituted with one or more halogen atoms, (9) C2-C6 cyanoalkyl optionally substituted with one or more halogen atoms, (10) C2-C6 alkoxyalkyl optionally substituted with one or more halogen atoms, (11) C2-C6 alkenyl optionally substituted with one or more halogen atoms, (12) C2-C6 alkynyl optionally substituted with one or more halogen atoms, (13) C3-C6 cycloalkyl optionally substituted with one or more halogen atoms, (14) C1-C6 alkylthio optionally substituted with one or more halogen atoms, (15) C1-C6 alkylsulfinyl optionally substituted with one or more halogen atoms, (16) C1-C6 alkylsulfonyl optionally substituted with one or more halogen atoms, (17) C1-C6 alkylamino, (18) C2-C8 dialkylamino, (19) C3-C6 cycloalkylamino, (20) C2-C6 alkylcarbonyl, (21) C2-C6 alkoxycarbonyl, (22) C2-C6 alkylaminocarbonyl, (23) C3-C8 dialkylaminocarbonyl, (24)
C4-C6 cycloalkylaminocarbonyl and (25) C3-C6 trialkylsilyl include benzyl, 1-phenylethyl, 2-phenylethyl, 2-chlorobenzyl, 3- chlorobenzyl, 4-chlorobenzyl, 2-cyanobenzyl, 3-cyanobenzyl, 4-cyanobenzyl, 2-nitrobenzyl, 3-nitrobenzyl, 4-nitrobenzyl, 2-methylbenzyl, 3-methylbenzyl, 4-methylbenzyl, 2- (trifluoromethyl) benzyl, 3- (trifluoromethyl) benzyl, 4- (trifluoromethyl) benzyl, 2-methoxybenzyl, 3-methoxybenzyl and 4-methoxybenzyl . Examples of phenoxy optionally substituted with one or more substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) hydroxyl, (5) carboxyl, (6) C1-C6 alkyl optionally substituted with one or more halogen atoms, (7) C1-C6 hydroxyalkyl, (8) Cl-Cβ alkoxy optionally substituted with one or more halogen atoms, (9) C2-C6 cyanoalkyl optionally substituted with one or more halogen atoms, (10) C2-C6 alkoxyalkyl optionally substituted with one or more halogen atoms, (11) C2-C6 alkenyl optionally substituted with one or more halogen atoms, (12) C2-C6 alkynyl optionally substituted with one or more halogen atoms, (13) C3-C6 cycloalkyl optionally substituted with one or more halogen atoms, (14) C1-C6 alkylthio optionally substituted with one or more halogen atoms, (15) C1-C6 alkylsulfinyl optionally substituted with one or more halogen atoms, (16) Cl-Cβ alkylsulfonyl optionally substituted with one or more halogen atoms, (17) Cl-Cβ alkylamino, (18) C2rC8 dialkylamino, (19) C3-C6 cycloalkylamino, (20) C2-C6 alkylcarbonyl, (21) C2-C6 alkoxycarbonyl, (22) C2-C6 alkylaminocarbonyl, (23) C3-C8 dialkylaminocarbonyl, (24) C4-C6 cycloalkylaminocarbonyl and (25) C3-C6 trialkylsilyl include phenoxy, 2-chlorophenoxy, 3-chlorophenoxy, 4-chlorophenoxy, 2-cyanophenoxy, 3-cyanophenoxy, 4-cyanophenoxy, 2- nitrophenoxy, 3-nitrophenoxy, 4-nitrophenoxy, 2- methylphenoxy, 3-methylphenoxy, 4-itιethylphenoxy, 2- (trifluoromethyl) phenoxy, 3- (trifluoromethyl) phenoxy, A- (trifluoromethyl) phenoxy, 2-methoxyphenoxy, 3- methoxyphenoxy, 4-methoxyphenoxy and A- (trifluoromethoxy) phenoxy
Examples of C7-C9 phenoxyalkyl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) C1-C6 alkyl optionally substituted with one or more halogen atoms and (5) C1-C6 alkoxy optionally substituted with one or more halogen atoms include phenoxymethyl, phenoxyethyl, 2-chlorophenoxymethyl, 2- chlorophenoxyethyl, 3-chlorophenoxymethyl, 3- chlorophenoxyethyl, 4-chlorophenoxymethyl, A- chlorophenoxyethyl, 2-cyanophenoxymethyl, 2- cyanophenoxyethyl, 3-cyanophenoxymethyl, 3- cyanophenoxyethyl, 4-cyanophenoxymethyl, A- cyanophenoxyethyl, 2-nitrophenoxymethyl, 2- nitrophenoxyethyl, 3-nitrophenoxymethyl, 3- nitrophenoxyethyl, 4-nitrophenoxymethyl, A- nitrophenoxyethyl, 2-methylphenoxymethyl, 2- methylphenoxyethyl, 3-methylphenoxymethyl, 3- methylphenoxyethyl, 4-methylphenoxymethyl, 4- methylphenoxyethyl, 2- ( trifluoromethyl) phenoxymethyl, 2-
( trifluoromethyl ) phenoxyethyl, 3-
(trifluoromethyl) phenoxymethyl, 3-
(trifluoromethyl ) phenoxyethyl, 4- (trifluoromethyl) phenoxymethyl, 4-
(trifluoromethyl) phenoxyethyl, 2-methoxyphenoxymethyl, 2- methoxyphenoxyethyl, 3-methoxyphenoxymethyl, 3- methoxyphenoxyethyl, 4-methoxyphenoxymethyl, 4- methoxyphenoxyethyl, 4- (trifluoromethoxy) phenoxymethyl and 4- (trifluoromethoxy) phenoxyethyl .
Examples of phenylcarbonyl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) hydroxyl, (5) carboxyl, (6) C1-C6 alkyl optionally substituted with one or more halogen atoms, (7) C1-C6 hydroxyalkyl, (8) C1-C6 alkoxy optionally substituted with one or more halogen atoms, (9) C2-C6 cyanoalkyl optionally substituted with one or more halogen atoms, (10) C2-C6 alkoxyalkyl optionally substituted with one or more halogen atoms, (11) C2-C6 alkenyl optionally substituted with one or more halogen atoms, (12) C2-C6 alkynyl optionally substituted with one or more halogen atoms, (13) C3-C6 cycloalkyl optionally substituted with one or more halogen atoms, (14) Cl-Cβ alkylthio optionally substituted with one or more halogen atoms, (15) C1-C6 alkylsulfinyl optionally substituted with one or more halogen atoms, (16) Cl-Cβ alkylsulfonyl optionally substituted with one or more halogen atoms, (17) C1-C6 alkylamino, (18) C2-C8 dialkylamino, (19) C3-C6 cycloalkylamino, (20) C2-C6 alkylcarbonyl, (21) C2-C6 alkoxycarbonyl, (22) C2-C6 alkylaminocarbonyl, (23) C3-C8 dialkylaminocarbonyl, (24) C4-C6 cycloalkylaminocarbonyl and (25) C3-C6 trialkylsilyl include benzoyl, 2-fluorobenzoyl, 3-fluorobenzoyl, 4-fluorobenzoyl, 2-chlorobenzoyl, 3-chlorobenzoyl, 4-chlorobenzoyl, 2- bromobenzoyl, 2-iodobenzoyl, 2, 6-difluorobenzoyl, 2,6- dichlorobenzoyl, 2-chloro-6-fluorobenzoyl, 2-chloro-4- fluorobenzoyl, 2-cyanobenzoyl, 3-cyanobenzoyl, 4- cyanobenzoyl, 2-nitrobenzoyl, 3-nitrobenzoyl, 4- nitrobenzoyl, 2-methylbenzoyl, 3-methylbenzoyl, 4- methylbenzoyl, 2-ethylbenzoyl, 2-isopropylbenzoyl, 2-tert- butylbenzoyl, 2- (trifluoromethyl) benzoyl, 3- (trifluoromethyl) benzoyl, 4- (trifluoromethyl) benzoyl, 2- methoxybenzoyl, 3-methoxybenzoyl, 4-methoxybenzoyl, 2- ethoxybenzoyl, 2- (trifluoromethoxy) benzoyl, 2- (methylthio) benzoyl, 2- (methylsulfinyl) benzoyl and 2- (methylsulfonyl) benzoyl .
Examples of naphthyl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) C1-C6 alkyl optionally substituted with one or more halogen atoms and (5) C1-C6 alkoxy optionally substituted with one or more halogen atoms include 1-naphthyl and 2-naphthyl.
Examples of 5- or 6-membered heteroaromatic ring optionally substituted with one or more substituents selected from the group consisting of (1) a halogen atom,
(2) cyano, (3) nitro, (4) hydroxyl, (5) carboxyl, (6) C1-C6 alkyl optionally substituted with one or more halogen atoms, (7) C1-C6 hydroxyalkyl, (8) C1-C6 alkoxy optionally substituted with one or more halogen atoms, (9) C2-C6 cyanoalkyl optionally substituted with one or more halogen atoms, (10) C2-C6 alkoxyalkyl optionally substituted with one or more halogen atoms, (11) C2-C6 alkenyl optionally substituted with one or more halogen atoms, (12) C2-C6 alkynyl optionally substituted with one or more halogen atoms, (13) C3-C6 cycloalkyl optionally substituted with one or more halogen atoms, (14) C1-C6 alkylthio optionally substituted with one or more halogen atoms, (15) C1-C6 alkylsulfinyl optionally substituted with one or more halogen atoms, (16) C1-C6 alkylsulfonyl optionally substituted with one or more halogen atoms, (17) C1-C6 alkylamino, (18) C2-C8 dialkylamino, (19) C3-C6 cycloalkylamino, (20) C2-C6 alkylcarbonyl, (21) C2-C6 alkoxycarbonyl, (22) C2-C6 alkylaminocarbonyl, (23) C3-C8 dialkylaminocarbonyl, (24) C4-C6 cycloalkylaminocarbonyl and (25) C3-C6 trialkylsilyl include
2-pyridinyl, 3-fluoro-2-pyridinyl, 3-chloro-2-pyridinyl, 3- bromo-2-pyridinyl, 3-iodo-2-pyridinyl, 3-methyl-2-pyridinyl, 3-trifluoromethyl-2-pyridinyl, 3-methoxy-2-pyridinyl, 3- cyano-2-pyridinyl, 3-nitro-2-pyridinyl, 3-pyridinyl, 2- chloro-3-pyridinyl, 4-chloro-3-pyridinyl, 4-pyridinyl, 3- chloro-4-pyridinyl, 3, 5-dichloro-4-pyridinyl, 2-pyrimidinyl, 4-methyl-2-pyrimidinyl, 4 , 6-dimethyl-2-pyrimidinyl, 4- pyrimidinyl, 5-chloro-4-pyrimidinyl, pyrazinyl, 3-methyl-2- pyrazinyl, 2-thiazolyl, l-methyl-5-pyrazolyl, 4-chloro-l- methyl-5-pyrazolyl, 4-chloro-l, 3-dimethyl-5-pyrazolyl and 4-chloro-5-methyl-3-isooxazolyl .
Examples of 3- to 8-membered non-aromatic heterocyclic ring optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, and (2) C1-C6 alkyl optionally substituted with one or more halogen atoms include pyrrolidin-1-yl, piperidino, 3, 5-dimethylpiperidino, hexamethyleneimin-1-yl, heptamethyleneimin-1-yl, morpholino, 2, 6-dimethylmorpholino, thiomorpholin-4-yl, 4- methylpiperazin-1-yl, 4- (ethoxycarbonyl) piperazin-1-yl and 4-phenylpiperazin-l-yl .
Examples of C7-C9 pyridinylalkyl whose pyridine ring is optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) C1-C6 alkyl optionally substituted with one or more halogen atoms, (5) C1-C6 alkoxy optionally substituted with one or more halogen atoms, (6) C1-C6 alkylthio optionally substituted with one or more halogen atoms, (7) C1-C6 alkylsulfinyl optionally substituted with one or more halogen atoms, (8) C1-C6 alkylsulfonyl optionally substituted with one or more halogen atoms, (9) C1-C6 alkylamino optionally substituted with one or more halogen atoms, (10) C2-C6 dialkylamino optionally substituted with one or more halogen atoms, (11) C2-C6 alkylcarbonyl optionally substituted with one or more halogen atoms, (12) C2-C6 alkoxycarbonyl optionally substituted with one or more halogen atoms, (13) C2-C6 alkylaminocarbonyl optionally substituted with one or more halogen atoms and (14) C3-C6 dialkylaminocarbonyl optionally substituted with one or more halogen atoms include 2-pyridinylmethyl, 3-pyridinylmethyl, 4-pyridinylmethyl , 3-chloro-2-pyridinylmethyl and 2-chloro-3-pyridinylmethyl . Examples of R2 and R3 are taken together with the two nitrogen atoms to which they are attached to form a 5 to 8 membered ring containing two nitrogen atoms, one or more CH2 or C (=0) , and optionally one or two ring members selected from the group consisting of (1) an oxygen atom, (2) a sulfur atom, (3) S (=0) , (4) S(=0)2 and (4) NRa are shown below as ring T. Said ring at the carbon atoms is substituted by one or more independent G6, which represents a halogen atom, C1-C6 alkyl optionally substituted with one or more halogen atoms, and C2-C6 alkoxycarbonyl optionally substituted with one or more halogen atoms. Further ring members from nitrogen -NRa- (not included the two contiguous linking nitrogen atoms) with free valences can be substituted by Ra which is selected from the group consisting of C1-C6 alkyl optionally substituted with one or more halogen atoms, C2-C6 alkoxycarbonyl optionally- substituted with one or more halogen atoms, or a phenyl optionally substituted with one or more independent substituents selected from the group consisting of a halogen atom, cyano, nitro, C1-C6 alkyl optionally substituted with one or more halogen atoms, C1-C6 alkoxy optionally substituted with one or more halogen atoms, Cl- C6 alkylthio optionally substituted with one or more halogen atoms, C1-C6 alkylsulfinyl optionally substituted with one or more halogen atoms, C1-C6 alkylsulfonyl optionally substituted with one or more halogen atoms, Cl- Cβ alkylamino optionally substituted with one or more halogen atoms, C2-C6 dialkylamino optionally substituted with one or more halogen atoms, C2-C6 alkylcarbonyl optionally substituted with one or more halogen atoms, C2- C6 alkoxycarbonyl optionally substituted with one or more halogen atoms, C2-C6 alkylaminocarbonyl optionally substituted with one or more halogen atoms and C3-C6 dialkylaminocarbonyl optionally substituted with one or more halogen atoms.
Figure imgf000051_0001
T-1 T-2 T-3 T-4 T-5 T-6
Figure imgf000051_0002
T-7 T-8 T-9 T-10 T-11 T-12
Figure imgf000051_0003
T-13 T-14 T-15 T-16 T-17 T-18
Figure imgf000051_0004
T-25 T-26 T-27 T-28 T-29 T-30
Figure imgf000051_0005
T-31 T-32 T-33 T-34 T-35
Said ring systems T are connected with the left upper nitrogen atom from the two contiguous linking nitrogen atoms via -(C=A2)- moiety with the ring system E, which represents, a 5- or 6-membered heteroaromatic ring system or a 8, 9 or 10-membered fused heterobicyclic ring system.
The substituent Q represents Ql, Q2, Q3, Q4 , Q5 or Q6:
Ql : C(=A31)—R6
Q2: C(=A32)—OR7
Q3: C(=A33)—SR8
Q4 : CC=A34J-NR9R10
Q5 : S(O)^r-R11
12r,13
Q6 : S(O)RT-NR1^R
A31, A32, A33 and A34 represent an oxygen atom, or a sulfur atom; m represents an integer of 0 to 2. Substituents R6 to R13 are selected as explained above in the summary of the invention.
J represents Jl or J2. Examples for said ring Jl and J2 are shown below as J-1.1 to J-1.8 and J-2.1 to J-2.8. The ring systems J-1.1 to J-1.8 and J-2.1 to J-2.8 are connected with their very left carbon atom via the -(C=A1)- group of the -NR1 (C=A1) J moiety with the ring system E, which represents, a 5- or 6-membered heteroaromatic ring system or a 8, 9 or 10-membered fused heterobicyclic ring system. One nitrogen atom is substituted by R19a (Jl) or R19b (J2) . Ring carbon atoms are optionally substituted by 1 to 3 substituents R20a (Jl) or R2Ob (J2) provided that, when 2 or 3 substituents R20a (Jl) or R2Ob (J2) are present, two or more R20a s and R20b's may be the same or different. Substituents R19a(Jl), R19b(J2), R20a(Jl) and R20b(J2) are selected as explained above in the summary of the invention.
Preferred ring systems include J-I.1, J-I.2, J-2.1 and J-2.2; most preferred J-I.1 and J-I.2.
J
Figure imgf000054_0001
Figure imgf000054_0002
J-1.1 J-1.2 J-1.3 J-1.4
Figure imgf000054_0003
J-1.5 J-1.6 J-1.7 J-1.8
Figure imgf000054_0004
J-2.1 J-2.2 J-2.3 J-2.4
Figure imgf000054_0005
J-2.5 J-2.6 J-2.7 J-2.8
Detailed examples of the group represented by Jl include l-phenylpyrazol-5-yl, 1- (2-chlorophenyl) pyrazol-5- yl, 1- (2-pyridinyl)pyrazol-5-yl, 1- (3-chloro-2- pyridinyl) pyrazol-5-yl, a 3-fluoro-l-phenylpyrazol-5-yl, 1- (2-chlorophenyl) -3-fluoropyrazol-5-yl, 3-fluoro-l- (2- pyridinyl) pyrazol-5-yl, 3-fluoro-l- (3-chloro-2- pyridinyl) pyrazol-5-yl, 3-chloro- l-phenylpyrazol-5-yl, 3-chloro-l- (2- chlorophenyl) pyrazol-5-yl, 3-chloro-l- (2- pyridinyl) pyrazol-5-yl, 3-chloro-l- (3-chloro-2- pyridinyl) pyrazol-5-yl, 3-bromo-l-phenylpyrazol-5-yl, 3- bromo-1- (2-chlorophenyl) pyrazol-5-yl, 3-bromo-l- (2- pyridinyl) pyrazol-5-yl, 3-bromo-l- (3-chloro-2- pyridinyl) pyrazol-5-yl, 3-iodo-l-phenylpyrazol-5-yl, 3- iodo-1- (2-chlorophenyl) pyrazol-5-yl, 3-iodo-l-(2- pyridinyl) pyrazol-5-yl, 3-iodo-l- (3-chloro-2- pyridinyl) pyrazol-5-yl, 3-methyl-l-phenylpyrazol-5-yl, 1- (2-chlorophenyl) -3-methylpyrazol-5-yl, 3-methyl-l- (2- pyridinyl) pyrazol-5-yl, 1- (3-chloro-2-pyridinyl) -3- methylpyrazol-5-yl, l-phenyl-3- (trifluoromethyl) pyrazol-5- yl, 1- (2-chlorophenyl) -3- (trifluoromethyl) pyrazol-5-yl, 1- (2-pyridinyl) -3- (trifluoromethyl) pyrazol-5-yl, 1- (3- chloro-2-pyridinyl) -3- (trifluoromethyl) pyrazol-5-yl, 3- chloro-1-methylpyrazol-5-yl, 3-chloro-l-ethylpyrazol-5-yl, 3-chloro-l-isopropylpyrazol-5-yl, l-tert-butyl-3- chloropyrazol-5-yl, 3-chloro-l- (3-fluoro-2- pyridinyl) pyrazol-5-yl, 1- ( 3-bromo-2-pyridinyl) -3- chloropyrazol-5-yl, 3-chloro-l- (3-iodo-2- pyridinyl) pyrazol-5-yl, 3-chloro-l- (3-methyl-2- pyridinyl) pyrazol-5-yl, 3-chloro-l- (3-trifluoromethyl-2- pyridinyl) pyrazol-5-yl, 3-chloro-l- (3-methoxy-2- pyridinyl) pyrazol-5-yl, 3-chloro-l- (3-cyano-2- pyridinyl) pyrazol-5-yl, 3-chloro-l- (3-nitro-2- pyridinyl) pyrazol-5-yl, 3-bromo-l-methylpyrazol-5-yl, 3- bromo-l-ethylpyrazol-5-yl, 3-bromo-l-isopropylpyrazol-5-yl, 3-bromo-l-tert-butylpyrazol-5-yl, 3-bromo-l- (3-fluoro-2- pyridinyl) pyrazol-5-yl, 3-bromo-l- (3-bromo-2- pyridinyl) pyrazol-5-yl, 3-bromo-l- (3-iodo-2- pyridinyl) pyrazol-5-yl, 3-bromo-l- (3-methyl-2- pyridinyl) pyrazol-5-yl, 3-bromo-l- (3-trifluoromethyl-2- pyridinyl) pyrazol-5-yl, 3-bromo-l- (3-methoxy-2- pyridinyl) pyrazol-5-yl, 3-bromo-l- (3-cyano-2- pyridinyl) pyrazol-5-yl, 3-bromo-l- (3-nitro-2- pyridinyl) pyrazol-5-yl, l-methyl-3- (trifluoromethyl) pyrazol-5-yl, l-ethyl-3-
(trifluoromethyl) pyrazol-5-yl, l-isopropyl-3-
(trifluoromethyl) pyrazol-5-yl, l-tert-butyl-3-
( trifluoromethyl) pyrazol-5-yl, 1- ( 3-fluoro-2-pyridinyl) -3-
(trifluoromethyl) pyrazol-5-yl, 1- (3-bromo-2-pyridinyl) -3- (trifluoromethyl) pyrazol-5-yl, l-(3-iodo-2- pyridinyl) -3- (trifluoromethyl) pyrazol-5-yl, 1- (3-methyl-2-pyridinyl) -3- (trifluoromethyl) pyrazol-5-yl, 1- (3-trifluoromethyl-2- pyridinyl) -3- (trifluoromethyl) pyrazol-5-yl, 1- (3-methoxy- 2-pyridinyl) -3- (trifluoromethyl) pyrazol-5-yl, 1- (3-cyano- 2-pyridinyl) -3- (trifluoromethyl) pyrazol-5-yl, l-(3-nitro- 2-pyridinyl) -3- ( trifluoromethyl) pyrazol- 5-yl, l-(3-chloro- 2-pyridinyl) -3-ethylpyrazol-5-yl, 1- (3-chloro-2- pyridinyl) -3-isopropylpyrazol-S-yl, 3-tert-butyl-l- (3- chloro-2-pyridinyl) pyrazol-5-yl, 1- (3-chloro-2-pyridinyl) - 3- (methylthio) pyrazol-5-yl, 1- (3-chloro-2-pyridinyl) -3- (ethylthio) pyrazol-5-yl, 1- (3-chloro-2-pyridinyl) -3- (isopropylthio) pyrazol-5-yl, 3-tert-butylthio-l- (3-chloro- 2-pyridinyl) pyrazol- 5-yl, 1- (3-chloro-2-pyridinyl) -3- (methylsulfinyl) pyrazol-5-yl, 1- (3-chloro-2-pyridinyl) -3- (ethylsulfinyl) pyrazol-5-yl, 1- (3-chloro-2-pyridinyl) -3- (isopropylsulfinyl) pyrazol-5-yl, 3-tert-butylsulfinyl-1- (3-chloro-2-pyridinyl) pyrazol-5-yl, 1- (3-chloro-2- pyridinyl) -3- (methylsulfonyl) pyrazol-5-yl, 1- (3-chloro-2- pyridinyl) -3- (ethylsulfonyl) pyrazol-5-yl, 1- (3-chloro-2- pyridinyl) -3- (isopropylsulfonyl) pyrazol-5-yl, 3-tert- butylsulfonyl-1- (3-chloro- 2-pyridinyl) pyrazol-5-yl, l-(3- chloro-2-pyridinyl) - 3- (2, 2, 2-trifluoroethoxy) pyrazol-5-yl, 1- (3-chloro- 2-pyridinyl) -3-cyanopyrazol-5-yl, l-(2- chlorophenyl) pyrrol-2-yl, 1- (3-chloro- 2-pyridinyl) pyrrol- 2-yl, 4-chloro-l- (2- chlorophenyl) pyrrol-2-yl, 4-chloro- 1- (3-chloro- 2-pyridinyl) pyrrol-2-yl, 5-chloro-l- (2- chlorophenyl) pyrrol-2-yl, 5-chloro-l- (3-chloro- 2- pyridinyl) pyrrol-2-yl, 1- (2-chlorophenyl) -4,5- dichloropyrrol-2-yl, 1- (3-chloro-2-pyridinyl) - 4,5- dichloropyrrol-2-yl, 4-bromo-l- (2- chlorophenyl) pyrrol-2- yl, 4-bromo-l- (3-chloro-2- pyridinyl) pyrrol-2-yl, 5- bromo-1- (2- chlorophenyl) pyrrol-2-yl, 5-bromo-l- (3-chloro- 2-pyridinyl) pyrrol-2-yl, 1- (2-chlorophenyl) -4,5- dibromopyrrol-2-yl, 1- (3-chloro-2-pyridinyl) - 4,5- dibromopyrrol-2-yl, 1- (2-chlorophenyl) -4- iodopyrrol-2-yl, 1- (3-chloro-2-pyridinyl) -4- iodopyrrol-2-yl, l-(2- chlorophenyl) -5- iodopyrrol-2-yl, 1- (3-chloro-2- pyridinyl) -5- iodopyrrol-2-yl, 1- (2-chlorophenyl) -4 , 5- diiodopyrrol-2-yl, 1- (3-chloro-2-pyridinyl) -4, 5- diiodopyrrol-2-yl, 1- (2-chlorophenyl) -4-
(trifluoromethyl) pyrrol-2-yl, 1- (3-chloro-2- pyridinyl) -4- (trifluoroinethyl) pyrrol-2-yl, 1- (2-chlorophenyl ) -5- (trifluoromethyl) pyrrol-2-yl, 1- (3-chloro-2-pyridinyl) -5- ( trifluoromethyl) pyrrol-2-yl, 1- (2-chlorophenyl) imidazol-2-yl, 1- (3-chloro-2- pyridinyl) imidazol-2-yl, 4-chloro-l- (2- chlorophenyl) imidazol-2-yl, 4-chloro-l- (3-chloro-2- pyridinyl) imidazol-2-yl, 4-bromo-l- (2- chlorophenyl) imidazol-2-yl, 4-bromo-l- (3-chloro-2- pyridinyl) imidazol-2-yl, 1- (2-chlorophenyl) -4-
(trifluoromethyl) imdazol-2-yl, 1- (3-chloro-2-pyridinyl) -A- (trifluoromethyl) imidazol-2-yl,
1- (2-chlorophenyl) -1,2, 4-triazol-5-yl, 1- (3-chloro-2- pyridinyl) -l,2,4-triazol-5-yl, 3-chloro-l- (2- chlorophenyl) -1,2, 4-triazol-5-yl, 3-chloro-l- (3-chloro-2- pyridinyl) -l,2,4-triazol-5-yl, 3-bromo-l- (2-chlorophenyl) - l,2,4-triazol-5-yl, 3-bromo-l- ( 3-chloro-2-pyridinyl ) - 1,2, 4-triazol-5-yl, 1- (2-chlorophenyl) -3- (trifluoromethyl) -1, 2, 4-triazol-5-yl and 1- (3-chloro-2- pyridinyl) -3- (trifluoromethyl) - 1, 2, 4-triazol-5-yl
Examples of the group represented by J2 include 1- methyl-3-phenylpyrazol-4-yl, 3- (2-chlorophenyl) -1- methylpyrazol-4-yl, l-methyl-3- (2-pyridinyl) pyrazol-4-yl, 3- (3-chloro-2-pyridinyl) -l-methylpyrazol-4-yl, l-methyl-5- phenylpyrazol-4-yl, 5- (2-chlorophenyl) -l-methylpyrazol-4-yl, 1-methyl-5- (2-pyridinyl) pyrazol-4-yl, 5- ( 3-chloro-2- pyridinyl) -l-methylpyrazol-4-yl, 3-phenyl-l- (2,2,2- trifluoroethyl) pyrazol-4-yl, 3- (2-chlorophenyl) -1- (2,2,2- trifluoroethyl) pyrazol-4-yl, 3- (2-pyridinyl) -1- (2, 2, 2- trifluoroethyl) pyrazol-4-yl, 3- (3-chloro-2- pyridinyl) -1- (2, 2, 2-trifluoroethyl) pyrazol-4-yl, 5-phenyl-l- (2,2,2- trifluoroethyl) pyrazol-4-yl, 5- (2-chlorophenyl) -1- (2,2,2- trifluoroethyl) pyrazol-4-yl, 5- (2-pyridinyl) -1- (2,2,2- trifluoroethyl) pyrazol- 4-yl, 5- (3-chloro-2-pyridinyl) -1- (2,2,2- trifluoroethyl) pyrazol-4-yl, 1- (difluoromethyl) -3- phenylpyrazol-4-yl, 3- (2-chlorophenyl) -1- (difluoromethyl) pyrazol-4-yl, 1- (difluoromethyl) - 3- (2- pyridinyl) pyrazol-4-yl, 3- (3-chloro-2- pyridinyl) -1- (difluoromethyl) pyrazol-4-yl, 1- (difluoromethyl) -5- phenylpyrazol-4-yl, 5- (2-chlorophenyl) -1- (difluoromethyl) pyrazol-4-yl, 1- (difluoromethyl) -5- (2- pyridinyl ) pyrazol-4-yl, 5- (3-chloro-2-pyridinyl) -1- (difluoromethyl) pyrazol-4-yl, 3- (2-chlorophenyl) -1- ethylpyrazol-4-yl, 3- (3-chloro-2-pyridinyl) -1-ethylpyrazol- 4-yl, 5- (2-chlorophenyl) -l-ethylpyrazol-4-yl, 5-(3-chloro- 2-pyridinyl) -l-ethylpyrazol-4-yl, 3- (2-chlorophenyl) -1- isopropylpyrazol-4-yl, 3- (3-chloro-2-pyridinyl) -1- isopropylpyrazol-4-yl, 5- (2-chlorophenyl) -1- isopropylpyrazol-4-yl, 5- (3-chloro-2-pyridinyl) -1- isopropylpyrazol-4-yl, 3- (2-chlorophenyl) -1-tert- butylpyrazol-4-yl, 3- (3-chloro-2-pyridinyl) -1-tert- butylpyrazol-4-yl, 5- (2-chlorophenyl) -1-tert-butylpyrazol- 4-yl and 5- (3-chloro-2-pyridinyl) -l-tert-butylpyrazol-4-yl
Hereinafter, preferred embodiments of the present invention are illustrated.
Preferred compounds are:
Preferred Compound 1: The compound according to the present compound, an i\7-oxide thereof or suitable salt thereof, wherein E is 5- or 6-membered heteroaromatic ring.
Preferred Compound 2: The compound according to the Preferred Compound 1, wherein A1 and A2 are oxygen atoms,
R1 is a hydrogen atom or alkyl optionally substituted with one or more halogen atoms.
Preferred Compound 3 : The compound according to the Preferred Compound 2, wherein J is J-I.1, J-I.2, J-2.1, J- 2.2 or J-2.3:
Figure imgf000061_0001
wherein R19a and R19b represent a hydrogen atom; C1-C6 alkyl optionally substituted with one or more halogen atoms; C3-C6 cycloalkyl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom and (2) C1-C6 alkyl optionally substituted with one or more halogen atoms; ■ phenyl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) C1-C6 alkyl optionally substituted with one or more halogen atoms, (5) C1-C6 alkoxy optionally substituted with one or more halogen atoms, (6) C1-C6 alkylthio optionally substituted with one or more halogen atoms, (7) C1-C6 alkylsulfinyl optionally substituted with one or more halogen atoms, (8) C1-C6 alkylsulfonyl optionally substituted with one or more halogen atoms, (9) C1-C6 alkylamino optionally substituted with one or more halogen atoms, (10) C2-C6 dialkylamino optionally substituted with one or more halogen atoms, (11) C2-C6 alkylcarbonyl optionally substituted with one or more halogen atoms, (12) C2-C6 alkoxycarbonyl optionally substituted with one or more halogen atoms, (13) C2-C6 alkylaminocarbonyl optionally substituted with one or more halogen atoms and (14) C3-C6 dialkylaminocarbonyl optionally substituted with one or more halogen atoms;
5- to 6-membered heteroaryl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) C1-C6 alkyl optionally substituted with one or more halogen atoms and (5) C1-C6 alkoxy optionally substituted with one or more halogen atoms; R20a and R20b represent a halogen atom, cyano, C1-C6 alkyl optionally substituted with one or more halogen atoms, Cl-Cβ alkoxy optionally substituted with one or more halogen atoms, C2-C6 cyanoalkyloxy, C2-C6 alkoxyalkyloxy optionally substituted with one or more halogen atoms, C2- C6 alkenyloxy optionally substituted with one or more halogen atoms, C1-C6 alkylthio optionally substituted with one or more halogen atoms, C1-C6 alkylsulfinyl optionally substituted with one or more halogen atoms, C1-C6 alkylsulfonyl optionally substituted with one or more halogen atoms, or phenyl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) C1-C6 alkyl optionally substituted with one or more halogen atoms and (5) C1-C6 alkoxy optionally substituted with one or more halogen atoms;
5- to 6-membered heteroaryl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) Cl-Cβ alkyl optionally substituted with one or more halogen atoms and (5) C1-C6 alkoxy optionally substituted with one or more halogen atoms or phenoxy optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) C1-C6 alkyl optionally substituted with one or more halogen atoms and (5) C1-C6 alkoxy optionally substituted with one or more halogen atoms; p represents an integer of 0 to 3, and q represents an integer of 0 to 3 (provided that, when p is an integer of 2 or 3, two or more R20a's may be the same or different and, when q is an integer of 2 or 3, two or more R20b's may be the same or different) .
Preferred Compound 4 : The compound according to the present compound, an N-oxide thereof or suitable salt thereof, wherein Q is Ql, A31 is oxygen and
R6 represents a hydrogen atom; C1-C6 alkyl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) C1-C6 alkoxy optionally substituted with one or more halogen atoms, (3) C1-C6 alkylthio optionally substituted with one or more halogen atoms, (4) C1-C6 alkylsulfinyl optionally substituted with one or more halogen atoms, (5) C1-C6 alkylsulfonyl optionally substituted with one or more halogen atoms, (6) C2-C6 dialkylamino optionally substituted with one or more halogen atoms, and (7) C3-C6 cycloalkyl optionally substituted with one or more halogen atoms;
C3-C6 cycloalkyl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, and (2) C1-C6 alkyl optionally substituted with one or more halogen atoms; phenyl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) C1-C6 alkyl optionally substituted with one or more halogen atoms, (5) C1-C6 alkoxy optionally substituted with one or more halogen atoms, (6) C1-C6 alkylthio optionally substituted with one or more halogen atoms, (7) C1-C6 alkylsulfinyl optionally substituted with one or more halogen atoms, (8) C1-C6 alkylsulfonyl optionally substituted with one or more halogen atoms, (9) C1-C6 alkylamino optionally substituted with one or more halogen atoms, (10) C2-C6 dialkylamino optionally substituted with one or more halogen atoms, (11) C2-C6 alkylcarbonyl optionally substituted with one or more halogen atoms, (12) C2-C6 alkoxycarbonyl optionally substituted with one or more halogen atoms, (13) C2-C6 alkylaminocarbonyl optionally substituted with one or more halogen atoms and (14) C3-C6 dialkylaminocarbonyl optionally substituted with one or more halogen atoms;
5- to 6-membered heteroaryl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) C1-C6 alkyl optionally substituted with one or more halogen atoms and (5) C1-C6 alkoxy optionally- substituted with one or more halogen atoms;
3- to 8-membered non-aromatic heterocyclic optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, and (2) C1-C6 alkyl optionally substituted with one or more halogen atoms or C7-C9 phenylalkyl or C7-C9 phenoxyalkyl : each said phenyl ring optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) C1-C6 alkyl optionally substituted with one or more halogen atoms and (5) C1-C6 alkoxy optionally substituted with one or more halogen atoms.
Preferred Compound 5: The compound according to the Preferred Compound 4, wherein A1 and A2 are oxygen atoms.
Preferred Compound 6: The compound according to the present compound, an N-oxide thereof or suitable salt thereof, wherein Q is Q2 , A32 is oxygen and R7 is C1-C6 alkyl optionally substituted with one or more halogen atoms; C2-C6 alkenyl optionally substituted with one or more halogen atoms; C3-C6 cycloalkyl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, and (2) C1-C6 alkyl optionally substituted with one or more halogen atoms; phenyl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) C1-C6 alkyl optionally substituted with one or more halogen atoms, (5) C1-C6 alkoxy optionally substituted with one or more halogen atoms, (6) C1-C6 alkylthio optionally substituted with one or more halogen atoms, (7) C1-C6 alkylsulfinyl optionally substituted with one or more halogen atoms, (8) C1-C6 alkylsulfonyl optionally substituted with one or more halogen atoms, (9) C1-C6 alkylamino optionally substituted with one or more halogen atoms, (10) C2-C6 dialkylamino optionally substituted with one or more halogen atoms, (11) C2-C6 alkylcarbonyl optionally substituted with one or more halogen atoms, (12) C2-C6 alkoxycarbonyl optionally substituted with one or more halogen atoms, (13) C2-C6 alkylaminocarbonyl optionally substituted with one or more halogen atoms and (14) C3-C6 dialkylaminocarbonyl optionally substituted with one or more halogen atoms;
5- to 6-membered heteroaryl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) C1-C6 alkyl optionally substituted with one or more halogen atoms and (5) C1-C6 alkoxy optionally substituted with one or more halogen atoms or C7-C9 phenylalkyl whose ring moiety is optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) C1-C6 alkyl optionally substituted with one or more halogen atoms and (5) C1-C6 alkoxy optionally substituted with one or more halogen atoms .
Preferred Compound 7: The compound according to the Preferred Compound 6, wherein A1 and A2 are oxygen atoms.
Preferred Compound 8: The compound according to the present compound, an 7\7-oxide thereof or suitable salt thereof, wherein Q is Q4 , A34 is oxygen and
R9 and R10 independently represent a hydrogen atom; C1-C6 alkyl optionally substituted with one or more halogen atoms; C3-C6 cycloalkyl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, and (2) C1-C6 alkyl optionally substituted with one or more halogen atoms; phenyl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) C1-C6 alkyl optionally substituted with one or more halogen atoms, (5) C1-C6 alkoxy optionally substituted with one or more halogen atoms, (6) C1-C6 alkylthio optionally substituted with one or more halogen atoms, (7) C1-C6 alkylsulfinyl optionally substituted with one or more halogen atoms, (8) Cl-Cβ alkylsulfonyl optionally substituted with one or more halogen atoms, (9) C1-C6 alkylamino optionally substituted with one or more halogen atoms, (10) C2-C6 dialkylamino optionally substituted with one or more halogen atoms, (11) C2-C6 alkylcarbonyl optionally substituted with one or more halogen atoms, (12) C2-C6 alkoxycarbonyl optionally substituted with one or more halogen atoms, (13) C2-C6 alkylaminocarbonyl optionally substituted with one or more halogen atoms and (14) C3-C6 dialkylaminocarbonyl optionally substituted with one or more halogen atoms;
5- to 6-membered heteroaryl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) C1-C6 alkyl optionally substituted with one or more halogen atoms and (5) C1-C6 alkoxy optionally substituted with one or more halogen atoms or C7-C9 phenylalkyl whose ring moiety is optionally- substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) C1-C6 alkyl optionally substituted with one or more halogen atoms and (5) C1-C6 alkoxy optionally substituted with one or more halogen atoms . Preferred Compound 9: The compound according to the Preferred Compound 8, wherein A1 and A2 are oxygen atoms.
Preferred Compound 10: A hydrazide compound represented by the formula (II-l) or (II-2),
Figure imgf000070_0001
wherein
Xa represents a nitrogen atom or CR20ax,
Y and Z represent independently a nitrogen atom or
CR4b, but not Y and Z are CR4b at the same time ,
R1 represets a hydrogen atom or C1 -C 6 alkyl optionally substituted with one or more halogen atoms , R2 and R3 independently represent a hydrogen atom, Cl- C6 alkyl optionally substituted with one or more halogen atoms, C2-C6 cyanoalkyl, C1-C6 hydroxyalkyl, C2-C6 alkoxyalkyl optionally substituted with one or more halogen atoms, C2-C6 alkenyl optionally substituted with one or more halogen atoms, C2-C6 alkynyl optionally substituted with one or more halogen atoms, C3-C6 cycloalkyl optionally substituted with one or more halogen atoms, C1-C6 alkylthio optionally substituted with one or more halogen atoms, Cl- C6 alkylsulfinyl optionally substituted with one or more halogen atoms, C1-C6 alkylsulfonyl optionally substituted with one or more halogen atoms, C2-C6 alkylcarbonyl optionally substituted with one or more halogen atoms, C2- C6 alkoxycarbonyl, C2-C6 alkylaminocarbonyl, C3-C8 dialkylaminocarbonyl, C4-C6 cycloalkylaminocarbonyl, or C3- C6 trialkylsilyl, or represents phenyl, C7-C9 phenylalkyl or phenylcarbonyl : each said phenyl ring optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) hydroxyl, (5) carboxyl, (6) C1-C6 alkyl optionally substituted with one or more halogen atoms, (7) C1-C6 hydroxyalkyl, (8) C1-C6 alkoxy optionally substituted with one or more halogen atoms, (9) C2-C6 cyanoalkyl, (10) C2-C6 alkoxyalkyl optionally substituted with one or more halogen atoms, (11) C2-C6 alkenyl optionally substituted with one or more halogen atoms, (12) C2-C6 alkynyl optionally substituted with one or more halogen atoms, (13) C3-C6 cycloalkyl optionally substituted with one or more halogen atoms, (14) C1-C6 alkylthio optionally substituted with one or more halogen atoms, (15) C1-C6 alkylsulfinyl optionally substituted with one or more halogen atoms, (16) C1-C6 alkylsulfonyl optionally substituted with one or more halogen atoms, (17) C1-C6 alkylamino, (18) C2-C8 dialkylamino, (19) C3-C6 cycloalkylamino, (20) C2-C6 alkylcarbonyl, (21) C2-C6 alkoxycarbonyl, (22) C2-C6 alkylaminocarbonyl, (23) C3-C8 dialkylaminocarbonyl, (24) C4-C6 cycloalkylaminocarbonyl and (25) C3-C6 trialkylsilyl or R2 and R3 are taken together with the two nitrogen atoms to which they are attached to form a 5 to 8 membered ring containing two nitrogen atoms, one or more CH2 or C(=O), and optionally one or two ring members selected from the group consisting of (1) an oxygen atom, (2) a sulfur atom, (3) S (=0) , (4) S(=0)2 and (4) NRa (wherein Ra represents C1-C6 alkyl optionally substituted with one or more halogen atoms, C2-C6 alkoxycarbonyl optionally substituted with one or more halogen atoms, or a phenyl optionally substituted with one or more independent substituents from (1) a halogen atom, (2) cyano, (3) nitro, (4) C1-C6 alkyl optionally substituted with one or more halogen atoms, (5) C1-C6 alkoxy optionally substituted with one or more halogen atoms, (6) C1-C6 alkylthio optionally substituted with one or more halogen atoms, (7) C1-C6 alkylsulfinyl optionally substituted with one or more halogen atoms, (8) Cl-Cβ alkylsulfonyl optionally- substituted with one or more halogen atoms, (9) C1-C6 alkylamino optionally substituted with one or more halogen atoms, (10) C2-C6 dialkylamino optionally substituted with one or more halogen atoms, (11) C2-C6 alkylcarbonyl optionally substituted with one or more halogen atoms, (12) C2-C6 alkoxycarbonyl optionally substituted with one or more halogen atoms, (13) C2-C6 alkylaminocarbonyl optionally substituted with one or more halogen atoms and (14) C3-C6 dialkylaminocarbonyl optionally substituted with one or more halogen atoms; and wherein the ring at the carbon atoms is optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) C1-C6 alkyl optionally substituted with one or more halogen atoms, and (3) C2-C6 alkoxycarbonyl optionally substituted with one or more halogen atoms;
R4a, R4b and R4c independently represent a halogen atom, cyano, nitro, hydroxyl, carboxyl, C1-C6 alkyl optionally substituted with one or more halogen atoms, C2-C6 alkoxy optionally substituted with one or more halogen atoms, C2- C6 cyanoalkyl , C2-C6 alkoxyalkyl optionally substituted with one or more halogen atoms, C2-C6 alkenyl optionally substituted with one or more halogen atoms, C2-C6 alkynyl optionally substituted with one or more halogen atoms, C3- C6 cycloalkyl optionally substituted with one or more halogen atoms, C1-C6 alkylthio optionally substituted with one or more halogen atoms, C1-C6 alkylsulfinyl optionally substituted with one or more halogen atoms, C1-C6 alkylsulfonyl optionally substituted with one or more halogen atoms, C1-C6 alkylamino, C2-C8 dialkylamino, C3-C6 cycloalkylamino, C2-C6 alkylcarbonyl optionally substituted with one or more halogen atoms, C2-C6 alkoxycarbonyl, C2-C6 alkylaminocarbonyl, C3-C8 dialkylaminocarbonyl, C3-C6 trialkylsilyl; or represents independently phenyl, benzyl, phenoxy, or 5- or 6-membered heteroaromatic ring, each ring optionally substituted with one or more substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) hydroxyl, (5) carboxyl, (6) C1-C6 alkyl optionally substituted with one or more halogen atoms, (7) C1-C6 hydroxyalkyl, (8) C1-C6 alkoxy optionally substituted with one or more halogen atoms, (9) C2-C6 cyanoalkyl, (10) C2-C6 alkoxyalkyl optionally substituted with one or more halogen atoms, (11) C2-C6 alkenyl optionally substituted with one or more halogen atoms, (12) C2-C6 alkynyl optionally substituted with one or more halogen atoms, (13) C3-C6 cycloalkyl optionally substituted with one or more halogen atoms, (14) C1-C6 alkylthio optionally substituted with one or more halogen atoms, (15) Cl-Cβ alkylsulfinyl optionally substituted with one or more halogen atoms, (16) C1-C6 alkylsulfonyl optionally- substituted with one or more halogen atoms, (17) C1-C6 alkylamino, (18) C2-C8 dialkylamino, (19) C3-C6 cycloalkylamino, (20) C2-C6 alkylcarbonyl, (21) C2-C6 alkoxycarbonyl, (22) C2-C6 alkylaminocarbonyl, (23) C3-C8 dialkylaminocarbonyl, (24) C4-C6 cycloalkylaminocarbonyl and (25) C3-C6 trialkylsilyl;
M is a hydrogen atom; C1-C6 alkyl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) C1-C6 alkoxy optionally substituted with one or more halogen atoms, (3) C1-C6 alkylthio optionally substituted with one or more halogen atoms, (4) C1-C6 alkylsulfinyl optionally substituted with one or more halogen atoms, (5) C1-C6 alkylsulfonyl optionally substituted with one or more halogen atoms, (6) C2-C6 dialkylamino optionally substituted with one or more halogen atoms, and (7) C3-C6 cycloalkyl optionally substituted with one or more halogen atoms; C1-C6 alkoxy optionally substituted with one or more halogen atoms; C1-C6 alkylthio optionally substituted with one or more halogen atoms; C1-C6 alkylamino; C2-C8 dialky1amino; phenyl, C7-C9 phenylalkyl or C7-C9 phenoxyalkyl : each said phenyl ring optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) C1-C6 alkyl optionally substituted with one or more halogen atoms, and (5) C1-C6 alkoxy optionally substituted with one or more halogen atoms;
5- to 6-membered heteroaryl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) C1-C6 alkyl optionally substituted with one or more halogen atoms, and (5) C1-C6 alkoxy optionally substituted with one or more halogen atoms; or 3- to 8-membered non-aromatic heterocyclic ring optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, and (2) C1-C6 alkyl optionally substituted with one or more halogen atoms;
R i9ax represents a hydrogen atom; C1-C6 alkyl optionally substituted with one or more halogen atoms; C2- C6 cyanoalkyl; C2-C6 alkoxyalkyl optionally substituted with one or more halogen atoms; C2-C6 alkenyl optionally substituted with one or more halogen atoms; C2-C6 alkynyl optionally substituted with one or more halogen atoms; C3- C6 cycloalkyl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, and (2) C1-C6 alkyl optionally substituted with one or more halogen atoms; phenyl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) C1-C6 alkyl optionally substituted with one or more halogen atoms, (5) C1-C6 alkoxy optionally substituted with one or more halogen atoms, (6) C1-C6 alkylthio optionally substituted with one or more halogen atoms, (7) C1-C6 alkylsulfinyl optionally substituted with one or more halogen atoms, (8) C1-C6 alkylsulfonyl optionally substituted with one or more halogen atoms, (9) Cl-Cβ alkylamino optionally substituted with one or more halogen atoms, (10) C2-C6 dialkylamino optionally substituted with one or more halogen atoms, (11) C2-C6 alkylcarbonyl optionally substituted with one or more halogen atoms, (12) C2-C6 alkoxycarbonyl optionally substituted with one or more halogen atoms, (13) C2-C6 alkylaminocarbonyl optionally substituted with one or more halogen atoms and (14) C3-C6 dialkylaminocarbonyl optionally substituted with one or more halogen atoms; 5- to 6-membered heteroaryl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) C1-C6 alkyl optionally substituted with one or more halogen atoms, (5) C1-C6 alkoxy optionally substituted with one or more halogen atoms, (6) C1-C6 alkylthio optionally substituted with one or more halogen atoms, (7) C1-C6 alkylsulfinyl optionally substituted with one or more halogen atoms, (8) Cl-Cβ alkylsulfonyl optionally substituted with one or more halogen atoms, (9) C1-C6 alkylamino optionally substituted with one or more halogen atoms, (10) C2-C6 dialkylamino optionally substituted with one or more halogen atoms, (11) C2-C6 alkylcarbonyl optionally substituted with one or more halogen atoms, (12) C2-C6 alkoxycarbonyl optionally substituted with one or more halogen atoms, (13) C2-C6 alkylaminocarbonyl optionally substituted with one or more halogen atoms and (14) C3-C6 dialkylaminocarbonyl optionally substituted with one or more halogen atoms; C7-C9 phenylalkyl whose phenyl ring is optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) C1-C6 alkyl optionally substituted with one or more halogen atoms, (5) C1-C6 alkoxy optionally substituted with one or more halogen atoms, (6) C1-C6 alkylthio optionally substituted with one or more halogen atoms, (7) C1-C6 alkylsulfinyl optionally substituted with one or more halogen atoms, (8) C1-C6 alkylsulfonyl optionally substituted with one or more halogen atoms, (9) C1-C6 alkylamino optionally substituted with one or more halogen atoms, (10) C2-C6 dialkylamino optionally substituted with one or more halogen atoms, (11) C2-C6 alkylcarbonyl optionally substituted with one or more halogen atoms, (12) C2-C6 alkoxycarbonyl optionally substituted with one or more halogen atoms, (13) C2-C6 alkylaminocarbonyl optionally substituted with one or more halogen atoms and (14) C3-C6 dialkylaminocarbonyl optionally substituted with one or more halogen atoms; or C7-C9 pyridinylalkyl whose pyridine ring is optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) C1-C6 alkyl optionally substituted with one or more halogen atoms, (5) C1-C6 alkoxy optionally substituted with one or more halogen atoms, (6) C1-C6 alkylthio optionally substituted with one or more halogen atoms, (7) C1-C6 alkylsulfinyl optionally substituted with one or more halogen atoms, (8) C1-C6 alkylsulfonyl optionally substituted with one or more halogen atoms, (9) C1-C6 alkylamino optionally substituted with one or more halogen atoms, (10) C2-C6 dialkylamino optionally substituted with one or more halogen atoms, (11) C2-C6 alkylcarbonyl optionally substituted with one or more halogen atoms, (12) C2-C6 alkoxycarbonyl optionally substituted with one or more halogen atoms, (13) C2-C6 alkylaminocarbonyl optionally substituted with one or more halogen atoms and (14) C3-C6 dialkylaminocarbonyl optionally substituted with one or more halogen atoms;
R20ax, R20ay and R20az represent a halogen atom; cyano ; nitro; thiocyanato; C1-C6 alkyl optionally substituted with one or more halogen atoms; C1-C6 alkoxy optionally substituted with one or more halogen atoms; C2-C6 cyanoalkyloxy; C2-C6 alkoxyalkyloxy optionally substituted with one or more halogen atoms; C2-C6 alkenyloxy optionally substituted with one or more halogen atoms; C2-C6 alkynyloxy optionally substituted with one or more halogen atoms; C1-C6 alkylthio optionally substituted with one or more halogen atoms; C1-C6 alkylsulfinyl optionally substituted with one or more halogen atoms; Cl-Cβ alkylsulfonyl optionally substituted with one or more halogen atoms; phenyl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) C1-C6 alkyl optionally substituted with one or more halogen atoms and (5) C1-C6 alkoxy optionally substituted with one or more halogen atoms;
5- to 6-membered heteroaryl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) C1-C6 alkyl optionally substituted with one or more halogen atoms and (5) C1-C6 alkoxy optionally substituted with one or more halogen atoms; or phenoxy optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) C1-C6 alkyl optionally substituted with one or more halogen atoms and (5) C1-C6 alkoxy optionally substituted with one or more halogen atoms.
Preferred Compound 11: The compound according to the Preferred Compound 10, wherein R1 is a hydrogen atom, R2 is a hydrogen atom or C1-C6 alkyl optionally substituted with one or more halogen atoms,
R3 is a hydrogen atom, C1-C6 alkyl optionally substituted with one or more halogen atoms or C2-C6 alkoxycarbonyl,
R4a is a halogen atom or C1-C6 alkyl optionally substituted with one or more halogen atoms,
R4c is a hydrogen atom, a halogen atom, cyano or Cl- C6 alkyl optionally substituted with one or more halogen atoms,
Figure imgf000082_0001
wherein Xb is a nitrogen atom or CR21a, R20aχ and R 20ay are independently a hydrogen atom, a halogen atom,- Cl-Cβ alkyl optionally substituted with one or more halogen atoms, C1-C6 alkoxy optionally substituted with one or more halogen atoms or C1-C6 alkylthio optionally substituted with one or more halogen atoms, R20az is a hydrogen atom,
R21a, R21b and R21c are independently selected from the group consisting of a hydrogen atom, a halogen atom or Cl- Cβ alkyl optionally substituted with one or more halogen atoms .
Preferred Compound 12: The compound according to the Preferred Compound 11, wherein Xa and Xb are nitrogen atoms, Y is CH and Z is a nitrogen atom.
Preferred Compound 13: The compound according to the Preferred Compound 11, wherein Xa and Xb are nitrogen atoms, Y is a nitrogen atom Z is CH and.
Preferred Compound 14: The compound according to the Preferred Compound 11, wherein R4b is a hydrogen atom.
Preferred Compound 15: The compound according to the Preferred Compound 14, wherein M is a hydrogen atom, C1-C6 alkyl, C1-C6 alkoxy, amino, C1-C6 alkylamino or C2-C8 dialkylamino .
Preferred Compound 16: The compound according to the Preferred Compound 15, wherein
R2 is a hydrogen atom, methyl or ethyl, R3 is a hydrogen atom, methyl, ethyl or methoxycarbonyl ,
R4a is methyl, chloro, bromo or iodo,
R4c is hydrogen, fluoro, chloro, bromo, iodo or cyano, R20ay ^3 ch]_orO/ bromo, iodo, trifluoromethyl or pentafluoroethoxy,
R22b is a hydrogen atom, R22c is chloro or bromo,
M is hydrogen, methoxy, ethoxy, methylamino or dimethylamino . Preferred Compound 17 : The compound of the Preferred Compound 16, wherein R2 is a hydrogen atom, R3 is methyl or ethyl and M is a hydrogen atom.
Preferred Compound 18: The compound of the Preferred Compound 17, wherein R2 and R3 are independently hydrogen, methyl or ethyl and
M is methoxy or ethoxy.
Preferred Compound 19: A hydrazide compound represented by the formula (II-l),
Xa, Y, Z, R1, R2, R3, R4a, R4b, R4c, M, R19ax, R20ax, R20ay, and R20az are discribed above.
Preferred Compound 20: The compound according to the Preferred Compound 19, wherein R1 is a hydrogen atom, R2 is a hydrogen atom or C1-C6 alkyl optionally substituted with one or more halogen atoms, R3 is a hydrogen atom, Cl-Cβ alkyl optionally substituted with one or more halogen atoms or C2-C6 alkoxycarbonyl ,
R4a is a halogen atom or Cl-Cβ alkyl optionally substituted with one or more halogen atoms, R4c is a hydrogen atom, a halogen atom, cyano or 1-C6 alkyl optionally substituted with one or more halogen atoms, R19a is
Figure imgf000085_0001
wherein Xb is a nitrogen atom or CR21a, R20aχ and R 20ay are inc}epenc}entIy a hydrogen atom, a halogen atom, C1-C6 alkyl optionally substituted with one or more halogen atoms, C1-C6 alkoxy optionally substituted with one or more halogen atoms or C1-C6 alkylthio optionally substituted with one or more halogen atoms, R20az is a hydrogen atom,
R21a, R21b and R21c are independently selected from the group consisting of a hydrogen atom, a halogen atom or Cl- C6 alkyl optionally substituted with one or more halogen atoms .
Preferred Compound 21: The compound according to the Preferred Compound 20, wherein Xa and Xb are nitrogen atoms,
Y is CH and
Z is a nitrogen atom.
Preferred Compound 22: The compound according to the Preferred Compound 20, wherein Xa and Xb are nitrogen atoms, Y is a nitrogen atom Z is CH and.
Preferred Compound 23: The compound according to the Preferred Compound 20, wherein R4b is a hydrogen atom.
Preferred Compound 24: The compound according to the Preferred Compound 23, wherein M is a hydrogen atom, Cl-Cβ alkyl, C1-C6 alkoxy, amino, C1-C6 alkylamino or C2-C8 dialkylamino .
Preferred Compound 25: The compound according to the Preferred Compound 24, wherein
R2 is a hydrogen atom, methyl or ethyl, R3 is a hydrogen atom, methyl, ethyl or methoxycarbonyl ,
R4a is methyl, chloro, bromo or iodo,
R4c is hydrogen, fluoro, chloro, bromo, iodo or cyano, R20ay is chloro, bromo, iodo, trifluoromethyl or pentafluoroethoxy,
R22b is a hydrogen atom, R22c is chloro or bromo,
M is hydrogen, methoxy, ethoxy, methylamino or dimethylamino . Preferred Compound 26: The compound of the Preferred Compound 25, wherein R2 is a hydrogen atom, R3 is methyl or ethyl and M is a hydrogen atom.
Preferred Compound 27 : The compound of the Preferred Compound 26, wherein R2 and R3 are independently hydrogen, methyl or ethyl and
M is methoxy or ethoxy.
This invention further pertains:
A pesticide comprising the present compound or , an N- oxide thereof or suitable salt thereof as an active ingredient . A method of controlling a pest which comprises applying the present compound, an iV-oxide thereof or suitable salt thereof directly to a pest, or to a place where a pest inhabits.
Use of the present compound, an N-oxide thereof or suitable salt thereof for controlling a pest.
Use of the present compound, an N-oxide thereof or suitable salt thereof for manufacturing a pesticidal preparation. Hereinafter, a process for producing the present compound will be explained.
The present compound can be produced, for example, by the following Process A-I to Process C-I. Process A-I
Among the present compounds, a compound represented by the formula (I) :
Figure imgf000088_0001
wherein R1, R2, R3, R4, A1, A2, J and n are as defined above, E represents, together with the two contiguous linking carbon atoms, a 5- or 6-membered heteroaromatic ring system or a 8 , 9 or 10-membered fused heterobicyclic ring system, Q' represents a group selected from the group consisting of Ql to Q6 (provided that the compound wherein Q' is Q4 , and R8 and R9 are a hydrogen atom is excluded) (hereinafter, referred to as the compound (I)) can be produced by reacting a compound represented by the formula (2) :
Figure imgf000089_0001
wherein R1, R2, R3, R4, A1, A2, J and n are as defined above (hereinafter, referred to as the compound (2)), and a compound represented by the formula (3) : L1—Q1 (3) wherein Q' is as defined above, and L1 represents a halogen atom or a Q' -O- (provided that the case where Q' is Q4, and R8 and R9 are a hydrogen atom is excluded) (hereinafter, referred to as the compound (3)) . The reaction is performed in the presence or the absence of a solvent. Examples of the solvent to be used in the reaction include ethers such as 1,4-dioxane, diethyl ether, tetrahydrofuran, methyl tert-butyl ether, and the like, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1, 2-dichloroethane, chlorobenzene, and the like, hydrocarbons such as toluene, benzene, xylene, and the like, nitriles such as acetonitrile and the like, aprotic polar solvents such as N, N-dimethylformamide, N-methlpyrrolidone, 1, 3-dimethyl-2- imidadzolidinone, dimethyl sulfoxide, and the like, and a mixture thereof. The amount of the compound (3) to be used in the reaction is usually 1 to 2 mols per 1 mol of the compound (2) .
The reaction is performed in the presence of a base, if necessary. Examples of the base include nitrogen- containing heterocyclic compounds such as pyridine, picoline, 2, 6-lutidine, 1, 8-diazabicyclo [5, 4, 0] 7-undecene (DBU), 1, 5-diazabicyclo[4, 3, 0] 5-nonene (DBN), and the like, tertiary amines such as triethylamine, N, N- diisopropylethylamine, and the like, and inorganic bases such as potassium carbonate, sodium hydride, and the like. The amount of the base when the reaction is performed in the presence of the base is usually 1 to 2 mols per 1 mol of the compound (2), while the base may be used in an excess amount in case that the base used is liquid under the reaction conditions such as pyridine, and the like.
The reaction temperature is usually in a range of 0 to 1000C, and the reaction time is usually in a range of 0.1 to 24 hours. After completion of the reaction, the compound (1-i) can be isolated by pouring the reaction mixture into water and extracting the mixture with an organic solvent, or collecting a deposited precipitate by filtration. The isolated compound (1-i) may be further purified by recrystallization, chromatography, or the like. Proces s A-2
Among the present compounds , a compound represented by the formula ( 1-ii ) :
Figure imgf000091_0001
wherein R1, R2, R3, R4, A1, A2, A34, J and n are as defined above, and R9a represents C1-C6 alkyl optionally substituted with at least one halogen atom; C2-C6 alkoxyalkyl optionally substituted with at least one halogen atom; C2-C6 alkenyl optionally substituted with at least one halogen atom; 3-C6 alkynyl optionally substituted with at least one halogen atom; C3-C6 cycloalkyl optionally- substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom and (2) C1-C6 alkyl group; a phenyl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom (2) cyano group, (3) nitro group, (4) Cl-Cβ alkyl optionally substituted with at least one halogen atom, (5) C1-C6 alkoxy optionally substituted with at least one halogen atom, (6) C1-C6 alkylthio optionally substituted with at least one halogen atom, (7) C1-C6 alkylsulfinyl optionally substituted with at least one halogen atom, (8) C1-C6 alkylsulfonyl optionally substituted with at least one halogen atom, (9) C2-C6 dialkylamino optionally substituted with at least one halogen atom and (10) C2-C6 alkoxycarbonyl optionally substituted with at least one halogen atom; 5- to 6- membered heteroaryl optionally substituted with one or more independent substituents selected from the group consisting of (1) halogen atom, (2) cyano group, (3) nitro group, (4) C1-C6 alkyl optionally substituted with at least one halogen atom and (5) C1-C6 alkoxy optionally substituted with at least one halogen atom; or C7-C9 phenylaklyl whose benzene ring moiety may be substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano group, (3) nitro group,
(4) C1-C6 alkyl optionally substituted with at least one halogen atom and (5) C1-C6 alkoxy optionally substituted with at least one halogen atom (hereinafter, referred to as the compound (1-ii)) can be produced by reacting the compound (2) with a compound represented by the formula (4) :
A34^C=N-R93 (4) wherein A34 and R9a are as defined above (hereinafter, referred to as the compound (4)) . The reaction is performed in the presence or the absence of a solvent. Examples of the solvent to be used in the reaction include ethers such as 1,4-dioxane, diethyl ether, tetrahydrofuran, methyl tert-butyl ether, and the like, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1, 2-dichloroethane, chlorobenzene, and the like, hydrocarbons such as toluene, benzene, xylene, and the like, nitriles such as acetonitrile, and the like, aprotic polar solvents such as N,N-dimethylformamide, N-methylpyrrolidone, 1, 3-dimethyl-2- imidazolidinone, dimethyl sulfoxide, and the like, and a mixture thereof.
The amount of the compound (4) used in the reaction is usually 1 to 2 mols per 1 mol of the compound (2) . The reaction temperature is usually in a range of 0 to 1000C, and the reaction time is a usually a range of 0.1 to 24 hours.
After completion of the reaction, the compound (1-ii) can be isolated by pouring the reaction mixture into water, and extracting the mixture with an organic solvent, or collecting a deposited precipitate by filtration. The isolated compound (1-ii) may be further purified by recrystallization, chromatography, or the like. Process A-3 Among the present compounds, a compound represented by the formula ( 1-iii ) :
Figure imgf000094_0001
wherein R1, R2, R3, R4, A1' A2, A34, J and n are as defined above (hereinafter, referred to as the compound (I-iii)) can be produced by reacting the compound (2) and a cyanate or a thiocyanate.
The reaction is performed in the presence of a solvent. Examples of the solvent used in the reaction include acids such as organic acids such as acetic acids, and the like and mineral acids such as hydrochloric acid, and the like, as well as a mixture of these acids and water, chloroform, or the like.
The amount of the cyanate or the thiocyanate used in the reaction is usually 1 to 2 mols per 1 mol of the compound (2) .
The reaction temperature is usually in a range of 0 to 1000C, and the reaction time is usually in a range of 0.1 to 24 hours.
Examples of the cyanate or the thiocyanate include potassium cyanate, sodium cyanate, ammonium cyanate, potassium thiocyanate, sodium thiocyanate and ammonium thiocyanate .
After completion of the reaction, the compound (I-iii) can be isolated by pouring the reaction mixture into water and extracting the mixture with an organic solvent, or collecting a deposited precipitate by filtration. The isolated Compound (I-iii) may be further purified by recrystallization, chromatography, or the like. Process B-I
The present compound can be produced by reacting a compound represented by the formula (6):
Figure imgf000095_0001
wherein R1, R2, R3, R4, A2, Q and n are as defined above
(hereinafter, referred to as Compound (6)) and a compound represented by the formula (7) :
L2—C—J
N1 (7) A1 wherein A and J are as define above, and L represents a halogen atom (hereinafter, referred to as the compound (7)).
The reaction is performed in the presence or the absence of a solvent. Examples of the solvent used in the reaction include ethers such as 1,4-dioxane, diethyl ether, tetrahydrofuran, methyl tert-butyl ether, and the like, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1, 2-dichloroethane, chlorobenzene, and the like, hydrocarbons such as toluene, benzene, xylene, and the like, nitriles such as acetonitrile, and the like, aprotic polar solvents such as N, N-dimethylformamide, N-methylpyrrolidone, 1, 3-dimethyl-2- imidazolidinone, dimethyl sulfoxide, and the like, and a mixture thereof.
The amount of the compound (7) used in the reaction is usually 1 to 2 mols per 1 mol of the compound (6) .
The reaction is performed in the presence of a base, if necessary. Examples of the base include nitrogen- containing heterocyclic compounds such as pyridine, picoline, 2, 6-lutidine, 1, 8-diazabicyclo [5, 4 , 0] 7-undecene (DBU), l,5-diazadicyclo[4,3,0] 5-nonene (DBN), and the like, tertiary amines such as triethylamine, N, N- diisopropylethylamine, and the like, and inorganic bases such as potassium carbonate, sodium hydride, and the like. The amount of the base when the reaction is performed in the presence of the base is usually 1 to 2 mole per 1 mol of the compound (6), while the base may be used in an excess amount in case that the base used is liquid under the reaction conditions such as pyridine, and the like.
The reaction temperature is usually in a range of 0 to 1000C, and the reaction time is usually in a range of 0.1 to 24 hours .
After completion of the reaction, the present compound can be isolated by pouring the reaction mixture into water, and extracting the mixture with an organic solvent, or collecting a deposited precipitation by filtration. The isolated present compound may be further purified by recrystallization, chromatography, or the like. Process B-2
Among the present compounds, a compound represented by the formula (I-iv) :
Figure imgf000097_0001
wherein R1, R2, R3, R4, A2, J, Q and n are as defined above (hereinafter referred to as the compound (I-iv) ) can be produced by reacting the compound (6) and a compound represented by the formula (8):
Figure imgf000097_0002
wherein J is as defined above (hereinafter, referred to as the compound (8)) in the presence of a dehydrating agent.
The reaction is performed in the presence or the absence of a solvent. Examples of the solvent to be used in the reaction include ethers such as 1,4-dioxane, diethyl ether, tetrahydrofuran, methyl tert-butyl ether, and the like, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1, 2-dichloroethane, chlorobenzene, and the like, hydrocarbons such as toluene, benzene, xylene, and the like, nitriles such as acetonitrile, and the like, aprotic polar solvents such as N,N-dimethylformamide, N-methylpyrrolidone, 1, 3-dimethyl-2- imidazolidinone, dimethyl sulfoxide, and the like, and a mixture thereof.
The amount of the compound (8) used in the reaction is usually 1 to 2 mols per 1 mol of the compound (6) .
Examples of the dehydrating agent to be used in the reaction include carbodiimides such as dicyclohexylcarbodiimide (DCC), l-ethyl-3- (3- dimethylaminopropyl) carbodiimide hydrochloride (WSC), and the like. The amount of the dehydrating agent to be used is usually 1 to 2 mols per 1 mol of the compound (6) .
The reaction temperature is usually in a range of 0 to 1000C, and the reaction time is usually in a range of 0.1 to 24 hours.
After completion of the reaction, the compound (I-iv) can be isolated by pouring the reaction mixture into water, and extracting the mixture with an organic solvent, or collecting a deposited precipitate by filtration. The isolated compound (1-iv) may be further purified by recrystallization, chromatography, or the like. Process C-I
Among the present compounds, a compound represented by the formula (1-v) :
Figure imgf000099_0001
wherein R2, R3, R4, J, Q and n are as defined above
(hereinafter, referred to as the compound (1-v)) can be produced by reacting a compound represented by the formula (9) :
Figure imgf000099_0002
wherein R4, J and n are as defined above (hereinafter, referred to as the compound (9) ) and a compound represented by the formula (10) :
Figure imgf000099_0003
wherein R2, R3 and Q are as defined above (hereinafter, referred to as the compound (10)). The reaction is performed in the presence or the absence of a solvent. Examples of the solvent used in the reaction include ethers such as 1,4-dioxane, diethyl ether, tetrahydrofuran, methyl tert-butyl ether, and the like, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1, 2-dichloroethane, chlorobenzene, and the like, hydrocarbons such as toluene, benzene, xylene, and the like, nitriles such as acetonitrile, and the like, aprotic polar solvents such as N,N-dimethylformamide, N-methylpyrrolidone, 1, 3-dimethyl-2- imidaozolidinone, dimethyl sulfoxide, and the like, and a mixture thereof.
The amount of the compound (10) to be used in the reaction is usually 1 to 20 mols per 1 mol of the compound (9).
The reaction temperature is usually in a range of 0 to 1000C, and the reaction time is usually in a range of 0.1 to 48 hours.
After completion of the reaction, the compound (1-v) can be isolated by pouring the reaction mixture into water, and extracting the mixture with an organic solvent, or collecting a deposited precipitate by filtration. The isolated compound (1-v) may be further purified by recrystallization, chromatography, or the like. Process C-2 Among the present compounds, a compound represented by the formula (1-vi) :
Figure imgf000101_0001
wherein R2, R3, R4, A1, J, Q and n are as defined above, R1 a represents C1-C6 alkyl optionally substituted with at least one halogen atom; C2-C6 cyanoalkyl group; C2-C6 alkoxyalkyl optionally substituted with at least one halogen atom; C2- C6 alkenyl optionally substituted with at least one halogen atom; C3-C6 alkynyl optionally substituted with at least one halogen atom; or C7-C9 phenylalkyl in which a benzene ring part may be substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano group, (3) nitro group, (4) Cl-Cβ alkyl optionally substituted with at least one halogen atom and (5) Cl-Cβ alkoxy optionally substituted with at least one halogen atom (hereinafter, referred to as the compound (1-vi)) can be produced by reacting a compound represented by the formula (11) :
Figure imgf000102_0001
wherein R1"3, R4, A1, J and n are as defined above, and L3 represents a halogen atom (hereinafter, referred to as the compound (H)) and the compound (10) . The reaction is performed in the presence or the absence of a solvent. Examples of the solvent to be used in the reaction include ethers such as 1,4-dioxane, diethyl ether, tetrahydrofuran, methyl tert-butyl ether, and the like, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1, 2-dichlorethane, chlorobenzene, and the like, hydrocarbons such as toluene, benzene, xylene, and the like, nitriles such as acetonitrile, and the like, aprotic polar solvents such as N, N-diethylformamide, N-methylpyrrolidone, 1, 3-dimethyl-2- imidazolidinone, dimethyl sulfoxide, and the like, and a mixture thereof.
The amount of the compound (10) to be used in the reaction is usually 1 to 2 mols per 1 mol of the compound
(H) • The reaction is performed in the presence of a base, if necessary. Examples of the base include nitrogen- containing heterocyclic compounds such as pyridine, picoline, 2, 6-lutidine, 1, 8-diazabicyclo [5, 4 , 0] 7-undecene (DBU), 1, 5-diazabicyclo[4, 3, 0] 5-nonene (DBN), and the like, tertiary amines such as triethylamine, N, N- diisopropylethylamine, and the like, and inorganic bases such as potassium carbonate, sodium hydride, and the like.
The amount of the base to be used when the reaction is performed in the presence of the base is usually 1 to 2 mols per 1 mol of the compound (11), while the base may be used in an excess amount in the case that the base used is liquid under the reaction conditions such as pyridine and the like.
The reaction temperature is usually in a range of 0 to
1000C, and the reaction time is usually in a range of 0.1 to 24 hours.
After completion of the reaction, the compound (1-vi) can be isolated after pouring the reaction mixture into water, and extracting the mixture with an organic solvent, or collecting a deposited precipitate by filtration. The isolated compound (1-vi) may be further purified by recrystallization, chromatography or the like.
Process C-3
The compound (1-vi) can also be produced by reacting a compound represented by the formula (12) :
Figure imgf000104_0001
wherein R4, R1 a' A1, J and n are as defined above (hereinafter, referred to as Compound (12)) and the compound (10) in the presence of a dehydrating agent. The reaction is performed in the presence or the absence of a solvent. Examples of the solvent to be used in the reaction include ethers such as 1,4-dioxane, diethyl ether, tetrahydrofuran, methyl tert-butyl ether, and the like, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1, 2-dichlroethane, chlorobenzene, and the like, hydrocarbons such as toluene, benzene, xylene, and the like, nitriles such as acetonitrile, and the like, aprotic polar solvents such as N, N-dimethylformamide, N-methylpyrrolidone, 1, 3-dimethyl-2- imidazolidinone, dimethyl sulfoxide, and the like, and a mixture thereof.
The amount of the compound (10) used in the reaction is usually 1 to 2 mols per 1 mol of the compound (12) .
Examples of the dehydrating agent used in the reaction include carbodiimides such as dicyclohexylcarbodiimide (DCC) , l-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (WSC), and the like. The amount of the dehydrating agent to be used is usually 1 to 2 mols per 1 mol of the compound (12) .
The reaction temperature is usually in a range of 0 to 1000C, and the reaction time is usually in a range of 0.1 to 24 hours.
After completion of the reaction, the compound (1-vi) can be isolated by pouring the reaction mixture into water and extracting the mixture with an organic solvent, or collecting a deposited precipitate by filtration. The isolated compound (1-vi) may be further purified by recrystallization, chromatography, or the like.
Then, a process for producing intermediates for producing the present compound will be explained. Reference Process 1
Among the compound (2), a compound represented by the formula (2-i) :
Figure imgf000105_0001
wherein R , R , R4, J and n are as defined above (hereinafter, referred to as the compound (2-i)) can be produced by reacting the compound (9) and a compound represented by the formula (13) :
Figure imgf000106_0001
wherein R2 and R3 are as defined above (hereinafter, referred to as the compound (13)). The reaction is performed in the presence or the absence of a solvent. Examples of the solvent used in the reaction include ethers such as 1,4-dioxane, diethyl ether, tetrahydrofuran, methyl tert-butyl ether, and the like, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1, 2-dichloroethane, chlorobenzene and the like, hydrocarbons such as toluene, benzene, xylene and the like, nitriles such as acetonitrile, and the like, aprotic polar solvents such as N, N- dimethylformamide, N-methylpyrrolidone, 1, 3-dimethyl-2- imidazolidinone, dimethyl sulfoxide, and the like, alcohols such as methanol, ethanol, 2-propanol, and the like, and a mixture thereof.
The amount of the compound (13) to be used in the reaction is usually 1 to 5 mols per 1 mol of the compound (9) .
The reaction temperature is usually in a range of -50 to 1000C, and the reaction time is usually in a range of 0.1 to 24 hours.
After completion of the reaction, the compound (2-i) can be isolated by pouring the reaction mixture into water, and extracting the mixture with an organic solvent, or collecting a deposited precipitate by filtration. The isolated compound (2-i) may be further purified by recrystallization, chromatography, or the like. Reference Process 2
Among the compound (2), a compound represented by the formula (2-ii) :
Figure imgf000107_0001
wherein R2, R3, R4, J and n are as defined above (hereinafter, referred to as Compound (2-ii)) can be produced by reacting a compound represented by the formula (14) :
Figure imgf000107_0002
wherein R , J and n are as defined above (hereinafter, referred to as the compound (14)) and the compound (13).
The reaction is performed in the presence or the absence of a solvent. Examples of the solvent to be used in the reaction include ethers such as 1,4-dioxane, diethyl ether, tetrahydrofuran, methyl tert-butyl ether, and the like, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1, 2-dichloroethane, chlorobenzene and the like, hydrocarbons such as toluene, benzene, xylene, and the like, nitriles such as acetonitrile, and the like, aprotic polar solvents such as N, N-dimethylformamide, N-methylpyrrolidone, 1, 3-dimethyl-2- imidazolidinone, dimethyl sulfoxide, and the like, alcohols such as methanol, ethanol, 2-propanol, and the like, and a mixture thereof.
The amount of the compound (13) to be used in the reaction is usually 1 to 5 mols per 1 mol of the compound (14) . The reaction temperature is usually in a range of -50 to 1000C, and the reaction time is usually in a range of 0.1 to 24 hours.
After completion of the reaction, the compound (2-ii) can be isolated by pouring the reaction mixture into water, and extracting the mixture with an organic solvent, or collecting a deposited precipitate by filtration. The isolated compound (2-ii) may be further purified by recrystallization, chromatography, or the like. Reference Process 3 Among the compound (2), a compound represented by the formula ( 2-iii ) :
Figure imgf000109_0001
wherein R1 a, R2, R3, R4, A1, J and n are as defined above (hereinafter, referred to as the compound (2-iii)) can be produced by reacting the compound (11) and the compound (13) .
The reaction is performed in the presence or the absence of a solvent. Examples of the solvent used in the reaction include ethers such as 1,4-dioxane, diethyl ether, tetrahydrofuran, methyl tert-butyl ether, and the like, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1, 2-dichloroethane, chlorobenzene, and the like, hydrocarbons such as toluene, benzene, xylene, and the like, nitriles such as acetonitrile, and the like, aprotic polar solvents such as N, N-dimethylformamide, N-methylpyrrolidone, 1, 3-dimethyl-2- imidazolidinone, dimethyl sulfoxide, and the like, and a mixture thereof.
The amount of Compound (13) used in the reaction is usually 2 to 10 mols per 1 mol of the compound (11) .
The reaction temperature is usually in a range of -50 to 1000C, and the reaction time is in a range of 0.1 to 24 hours .
After completion of the reaction, the compound (2-iii) can be isolated by pouring the reaction mixture into water, and extracting the mixture with an organic solvent, or collecting a deposited precipitate by filtration. The isolated compound (2-iii) may be further purified by recrystallization, chromatography, or the like. Reference Process 4 The compound (9) can be produced by reacting a compound represented by the formula (16) .
Figure imgf000110_0001
wherein R4 and n are as defined above (hereinafter, referred to as the compound (16)) and a compound represented by the formula (7') :
Figure imgf000110_0002
wherein J and L2 are as defined above (hereinafter, referred to as Compound (7')).
The reaction is performed in the presence or the absence of a solvent in the presence of a base. Examples of the solvent to be used in the reaction include ethers such as 1,4-dioxane, diethyl ether, tetrahydrofuran, methyl tert-butyl ether, and the like, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1, 2-dichloroethane, chlorobenzene, and the like, hydrocarbons such as toluene, benzene, xylene, and the like, nitriles such as acetonitrile, and the like, aprotic polar solvents such as N, N-dimethylformamide, N-methylpyrrolidone, 1, 3-dimethyl-2-imidazolidinone, dimethyl sulfoxide, and the like, and a mixture thereof.
The amount of the compound (7') used in the reaction is usually 0.5 to 2 mols per 1 mol of the compound (16) .
Examples of the base to be used in the reaction include nitrogen-containing heterocyclic compounds such as pyridine, picoline, 2, 6-lutidine, 1, 8-diazabicyclo [5, 4 , 0] 7- undecene (DBU) , 1, 5-diazabicyclo [4 , 3, 0] 5-nonene (DBN), and the like, tertiary amines such as triethylamine, N, N- diisopropylethylamine, and the like, and inorganic bases such as potassium carbonate, sodium hydride, and the like. The amount of the base to be used is usually 1 to 2 mols per 1 mol of the compound (16), while the base may be used in an excess amount in case that the base is liquid under the reaction conditions such as pyridine, and the like. The reaction temperature is usually in a range of 50 to 15O0C, and the reaction time is usually in a range of 1 to 24 hours.
After completion of the reaction, the compound (9) can be isolated by pouring the reaction mixture into water, and extracting the mixture with an organic solvent, or collecting a deposited precipitates by filtration. The isolated compound (9) may be further purified by recrystallization, chromatography, or the like. Reference Process 5 The compound (9) can be produced by reacting a compound represented by the formula (17) :
Figure imgf000112_0001
wherein R4 and n are as defined above (hereinafter, referred to as Compound (17)) and the compound (7'). The reaction is performed in the presence or the absence of a solvent. Examples of the solvent to be used in the reaction include ethers such as 1,4-dioxane, diethyl ether, tetrahydrofuran, methyl tert-butyl ether, and the like, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1, 2-dichloroethane, chlorobenzene, and the like, hydrocarbons such as toluene, benzene, xylene, and the like, nitriles such as acetonitrile, and the like, aprotic polar solvents such as N,N-dimethylformamide, N-methylpyrrolidone, 1, 3-dimethyl-2- imidazolidinone, dimethyl sulfoxide, and the like, and a mixture thereof. The process comprises the following step 5-1 and step 5-2. Step 5-1
This step is performed by reacting the compound (17) and the compound (7') in the presence of a base. The amount of the compound (7') to be used in this step is usually 1 to 2 mols per 1 mol of the compound (17) . Examples of the base include nitrogen-containing heterocyclic compounds such as pyridine, picoline, 2,6- lutidine, 1, 8-diazabicyclo [5, 4 , 0] 7-undecene (DBU), 1,5- diazabicyclo [4 , 3, 0] 5-nonene (DBN), and the like, tertiary amines such as triethylamine, N, N-diisopropylethylamine, and the like, and inorganic bases such as potassium carbonate, sodium hydride, and the like. The amount of the base to be used is usually 1 to 2 mols per 1 mol of the compound (17) .
The reaction temperature of this step is usually in a range of 0 to 500C, and the reaction time is usually in a range of 0.1 to 24 hours.
After completion of this step, usually, the reaction mixture is used as it is in the next step 5-2. Step 5-2
This step is performed by reacting the reaction mixture in the step 5-1 and a sulfonyl halide in the presence of a base. Examples of the sulfonyl halide used in this step include methanesulfonyl chloride, p-toluenesulfonyl chloride, and trifluoromethanesulfonyl chloride. The amount of the sulfonyl halide to be used in this step is usually 1 to 2 mols per 1 mol of the compound (17) used in the step 5-1.
Examples of the base include the same bases as those described with respect to the step 5-1. The amount of the base is usually 2 to 4 mols per 1 mol of the compound (17) used in the step 5-1. The reaction temperature of this step is usually in a range of 0 to 500C, and the reaction time is usually in a range of 0.1 to 24 hours.
After completion of this step, the compound (9) can be isolated by pouring the reaction mixture into water, followed by conventional extraction with an organic solvent.
The isolated compound (9) may be further purified by recrystallization, chromatography, or the like.
Reference Process 6
The compound (14) can be produced by reacting the compound (9) with a thiocarbonylation agent. The reaction is performed in the presence or the absence of a solvent. Examples of the solvent to be used in the reaction include ethers such as 1,4-dioxane, diethyl ether, tetrahydrofuran, methyl tert-butyl ether, diglyme, and the like, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1,2- dichloroethane, chlorobenzene, and the like, hydrocarbons such as toluene, benzene, xylene, and the like, nitriles such as acetonitrile, and the like, pyridines such as pyridine, picoline, lutidine, and the like, and a mixture thereof.
Examples of the thiocarbonylation agent to be used in the reaction include diphosphorus pentasulfide, a Lawesson's reagent (2, 4-bis- (4-methoxyphenyl) -1, 3-dithia- 2, 4-diphosphetane 2, 4-disulfide) , and the like.
The amount of the thiocarbonylation agent to be used in the reaction is usually 1 to 3 mols per 1 mol of the compound ( 9) .
The reaction temperature is usually in a range of 00C to 2000C, and the reaction time is usually in a range of 1 to 24 hours.
After completion of the reaction, the compound (14) can be isolated by collecting a precipitate deposited in the reaction mixture by filtration, or extracting the reaction mixture with an organic solvent. The isolated compound (14) may be further purified by recrystallization, chromatography, or the like. Reference Process 7
The compound (11) can be produced by reacting the compound (12) with a halogenating agent.
The reaction is performed in the presence or the absence of a solvent. Examples of the solvent to be used in the reaction include ethers such as 1,4-dioxane, diethyl ether, tetrahydrofuran, methyl tert-butyl ether, and the like, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1, 2-dichloroethane, chlorobenzene, and the like, hydrocarbons such as toluene, benzene, xylene, and the like, nitriles such as acetonitrile, and the like, aprotic polar solvents such as N, N-dimethylformamide, N-methylpyrrolidone, 1, 3-dimethyl-2- imidazolidinone, dimethyl sulfoxide, and the like, and a mixture thereof.
Examples of the halogenating agent to be used in the reaction include thionyl chloride, thionyl bromide, phosphorus oxychloride, phosphorus oxybromide, phosphorus pentachloride, oxalyl chloride, and phosgene.
The amount of the halogenating agent to be used in the reaction is usually 1 to 2 mols per 1 mol of the compound (12) and, in some cases, the halogenating agent may be used in an excess amount. The reaction temperature is usually in a range of 00C to 1500C, and the reaction time is usually in a range of 0.1 to 24 hours.
After completion of the reaction, the compound (11) can be isolated by collecting a precipitate deposited in the reaction mixture, or concentrating the reaction mixture. The isolated compound (11) is usually used as it is in the next step and, if necessary, may be further purified by recrystallization, or the like. Reference Process 8
The compound (12) can be produced by reacting a compound represented by the formula (18'):
Figure imgf000117_0001
wherein R1"3, R4 and n are- as defined above (hereinafter, referred to as the compound (18')) and the compound (7).
The reaction is performed in the presence or the absence of a solvent. Examples of the solvent used in the reaction include ethers such as 1,4-dioxane, diethyl ether, tetrahydrofuran, methyl tert-butyl ether, and the like, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1, 2-dichloroethane, chlorobenzene, and the like, hydrocarbons such as toluene, benzene, xylene, and the like, nitriles such as acetonitrile, and the like, aprotic polar solvents such as N, N-dimethylformamide, N-methylpyrrolidone, 1, 3-dimethyl-2- imidazolidinone, dimethyl sulfoxide, and the like, and a mixture thereof.
The amount of the compound (7) to be used in the reaction is usually 1 to 2 mols per 1 mol of the compound (18') . The reaction is performed in the presence of a base. Examples of the base to be used include nitrogen-containing heterocyclic compounds such as pyridine, picoline, 2,6- lutidine, 1, 8-diazabicyclo [5, 4 , 0] 7-undecene (DBU), 1,5- diazabicyclo [4 , 3, 0] 5-nonene (DBN), and the like, tertiary amines such as triethylamine, N,N-diisopropylethylamine, and the like, inorganic bases such as potassium carbonate, sodium hydride, and the like. The amount of the base to be used is usually 1 to 2 mols per 1 mol of the compound (18') .
The reaction temperature is usually in a range of 0 to 500C, and the reaction time is usually in range of 0.1 to 24 hours.
After completion of the reaction, the compound (12) can be isolated by pouring the reaction mixture into water, followed by conventional extraction with an organic solvent, or collecting a deposited precipitate by filtration. The isolated compound (12) may be further purified by recrystallization, chromatography, or the like. Reference Process 9
The compound (6) can be produced by reacting a compound represented by the formula (20) :
Figure imgf000119_0001
wherein R1, R4 and n are as defined above (hereinafter, referred to as the compound 20)) and the compound (10).
The reaction is performed in the presence or the absence of a solvent. Examples of the solvent used in the reaction include ethers such as 1,4-dioxane, diethyl ether, tetrahydrofuran, methyl tert-butyl ether, and the like, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1, 2-dichloroethane, chlorobenzene, and the like, hydrocarbons such as toluene, benzene, xylene, and the like, nitriles such as acetonitrile, and the like, aprotic polar solvents such as N, N-dimethylformamide, N-methylpyrrolidone, 1, 3-dimethyl-2- imidazolidinone, dimethyl sulfoxide, and the like, alcohols such as methanol, ethanol, isopropyl alcohol, and the like, and a mixture thereof. The amount of the compound (10) to be used in the reaction is usually 1 to 2 mols per 1 mol of the compound (20) .
The reaction temperature is usually in a range of -20 to 1500C, and the reaction time is usually in a range of 0.1 to 24 hours.
After completion of the reaction, the compound (20) can be isolated by pouring the reaction mixture into water, and extracting the mixture with an organic solvent, or collecting a deposited precipitate by filtration. The isolated Compound (20) may be further purified by recrystallization, chromatography, or the like.
The compounds (3), (4) and (13) are known compounds, or can be produced from known compounds according to known processes (e.g. see Organic Functional Group Preparations, 2nd edition, Vol.l, chapter 12, p.359-376 (Stanley R. Sandler, Wolf Karo.) or Organic Functional Group Preparations, 2nd edition, Vol.l, chapter 14, p.434-465 (Stanley R. Sandler, Wolf Karo.)). As an aspect of the compound (2), the following compound is mentioned:
A hydrazide compound of the formula (II) :
Figure imgf000121_0001
wherein
Xa represents a nitrogen atom or CR20ax,
Y and Z represent independently a nitrogen atom or CR4b, but not Y and Z are CR4b at the same time,
R1 is a hydrogen atom or C1-C6 alkyl optionally- substituted with one or more halogen atoms,
R2 represent a hydrogen atom, C1-C6 alkyl optionally substituted with one or more halogen atoms, C2-C6 cyanoalkyl, C1-C6 hydroxyalkyl, C2-C6 alkoxyalkyl optionally substituted with one or more halogen atoms, C2- C6 alkenyl optionally substituted with one or more halogen atoms, C2-C6 alkynyl optionally substituted with one or more halogen atoms, C3-C6 cycloalkyl optionally substituted with one or more halogen atoms, C1-C6 alkylthio optionally substituted with one or more halogen atoms, C1-C6 alkylsulfinyl optionally substituted with one or more halogen atoms, C1-C6 alkylsulfonyl optionally substituted with one or more halogen atoms, C2-C6 alkylcarbonyl optionally substituted with one or more halogen atoms, C2- C6 alkoxycarbonyl, C2-C6 alkylaminocarbonyl, C3-C8 dialkylaminocarbonyl , C4-C6 cycloalkylaminocarbonyl, or C3- C6 trialkylsilyl, or represents phenyl, C7-C9 phenylalkyl or phenylcarbonyl : each said phenyl ring optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) hydroxyl, (5) carboxyl, (6) C1-C6 alkyl optionally substituted with one or more halogen atoms, (7) Cl-Cβ hydroxyalkyl, (8) C1-C6 alkoxy optionally substituted with one or more halogen atoms, (9) C2-C6 cyanoalkyl, (10) C2-C6 alkoxyalkyl optionally substituted with one or more halogen atoms, (11) C2-C6 alkenyl optionally substituted with one or more halogen atoms, (12) C2-C6 alkynyl optionally substituted with one or more halogen atoms, (13) C3-C6 cycloalkyl optionally substituted with one or more halogen atoms, (14) C1-C6 alkylthio optionally substituted with one or more halogen atoms, (15) C1-C6 alkylsulfinyl optionally substituted with one or more halogen atoms, (16) C1-C6 alkylsulfonyl optionally substituted with one or more halogen atoms, (17) C1-C6 alkylamino, (18) C2-C8 dialkylamino, (19) C3-C6 cycloalkylamino, (20) C2-C6 alkylcarbonyl, (21) C2-C6 alkoxycarbonyl, (22) C2-C6 alkylaminocarbonyl, (23) C3-C8 dialkylaminocarbonyl, (24) C4-C6 cycloalkylaminocarbonyl and (25) C3-C6 trialkylsilyl
R4a, R4b and R4c are independently a halogen atom, cyano, nitro, hydroxyl, carboxyl, C1-C6 alkyl optionally substituted with one or more halogen atoms, C1-C6 alkoxy optionally substituted with one or more halogen atoms, C2- C6 cyanoalkyl , C2-C6 alkoxyalkyl optionally substituted with one or more halogen atoms, C2-C6 alkenyl optionally substituted with one or more halogen atoms, C2-C6 alkynyl optionally substituted with one or more halogen atoms, C3- C6 cycloalkyl optionally substituted with one or more halogen atoms, C1-C6 alkylthio optionally substituted with one or more halogen atoms, C1-C6 alkylsulfinyl optionally substituted with one or more halogen atoms, C1-C6 alkylsulfonyl optionally substituted with one or more halogen atoms, C1-C6 alkylamino, C2-C8 dialkylamino, C3-C6 cycloalkylamino, C2-C6 alkylcarbonyl optionally substituted with one or more halogen atoms, C2-C6 alkoxycarbonyl, C2-C6 alkylaminocarbonyl, C3-C8 dialkylaminocarbonyl, C3-C6 trialkylsilyl or represents independently phenyl, benzyl or phenoxy, each ring optionally substituted with one or more substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) hydroxyl, (5) carboxyl, (6) C1-C6 alkyl optionally substituted with one or more halogen atoms, (7) C1-C6 hydroxyalkyl, (8) C1-C6 alkoxy optionally substituted with one or more halogen atoms, (9) C2-C6 cyanoalkyl, (10) C2-C6 alkoxyalkyl optionally substituted with one or more halogen atoms, (11) C2-C6 alkenyl optionally substituted with one or more halogen atoms, (12) C2-C6 alkynyl optionally substituted with one or more halogen atoms, (13) C3-C6 cycloalkyl optionally substituted with one or more halogen atoms, (14) C1-C6 alkylthio optionally substituted with one or more halogen atoms, (15) C1-C6 alkylsulfinyl optionally substituted with one or more halogen atoms, (16) Cl-Cβ alkylsulfonyl optionally substituted with one or more halogen atoms, (17) C1-C6 alkylamino, (18) C2-C8 dialkylamino, (19) C3-C6 cycloalkylamino, (20) C2-C6 alkylcarbonyl, (21) C2-C6 alkoxycarbonyl, (22) C2-C6 alkylaminocarbonyl, (23) C3-C8 dialkylaminocarbonyl, (24)
C4-C6 cycloalkylaminocarbonyl and (25) C3-C6 trialkylsilyl; or 5- or β-membered heteroaromatic optionally substituted with one or more substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) hydroxyl, (5) carboxyl, (6) C1-C6 alkyl optionally substituted with one or more halogen atoms, (7) C1-C6 hydroxyalkyl, (8) C1-C6 alkoxy optionally substituted with one or more halogen atoms, (9) C2-C6 cyanoalkyl, (10) C2-C6 alkoxyalkyl optionally substituted with one or more halogen atoms, (11) C2-C6 alkenyl optionally substituted with one or more halogen atoms, (12) C2-C6 alkynyl optionally substituted with one or more halogen atoms, (13) C3-C6 cycloalkyl optionally substituted with one or more halogen atoms, (14) C1-C6 alkylthio optionally substituted with one or more halogen atoms, (15) C1-C6 alkylsulfinyl optionally substituted with one or more halogen atoms, (16) C1-C6 alkylsulfonyl optionally substituted with one or more halogen atoms, (17) C1-C6 alkylamino, (18) C2-C8 dialkylamino, (19) C3-C6 cycloalkylamino, (20) C2-C6 alkylcarbonyl, (21) C2-C6 alkoxycarbonyl, (22) C2-C6 alkylaminocarbonyl, (23) C3-C8 dialkylaminocarbonyl, (24) C4-C6 cycloalkylaminocarbonyl and (25) C3-C6 trialkylsilyl;
R19ax represent a hydrogen atom; C1-C6 alkyl optionally substituted with one or more halogen atoms; C2- C6 cyanoalkyl; C2-C6 alkoxyalkyl optionally substituted with one or more halogen atoms; C2-C6 alkenyl optionally substituted with one or more halogen atoms; C2-C6 alkynyl optionally substituted with one or more halogen atoms; C3- C6 cycloalkyl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, and (2) C1-C6 alkyl optionally substituted with one or more halogen atoms; phenyl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) C1-C6 alkyl optionally substituted with one or more halogen atoms, (5) C1-C6 alkoxy optionally substituted with" one or more halogen atoms, (6) Cl-Cβ alkylthio optionally substituted with one or more halogen atoms, (7) C1-C6 alkylsulfinyl optionally substituted with one or more halogen atoms, (8) C1-C6 alkylsulfonyl optionally substituted with one or more halogen atoms, (9) C1-C6 alkylamino optionally substituted with one or more halogen atoms, (10) C2-C6 dialkylamino optionally substituted with one or more halogen atoms, (11) C2-C6 alkylcarbonyl optionally substituted with one or more halogen atoms, (12) C2-C6 alkoxycarbonyl optionally substituted with one or more halogen atoms, (13) C2-C6 alkylaminocarbonyl optionally substituted with one or more halogen atoms and (14) C3-C6 dialkylaminocarbonyl optionally substituted with one or more halogen atoms;
5- to 6-membered heteroaryl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) C1-C6 alkyl optionally substituted with one or more halogen atoms, (5) C1-C6 alkoxy optionally substituted with one or more halogen atoms, (6) C1-C6 alkylthio optionally substituted with one or more halogen atoms, (7) C1-C6 alkylsulfinyl optionally substituted with one or more halogen atoms, (8) Cl-Cβ alkylsulfonyl optionally substituted with one or more halogen atoms, (9) C1-C6 alkylamino optionally substituted with one or more halogen atoms, (10) C2-C6 dialkylamino optionally substituted with one or more halogen atoms, (11) C2-C6 alkylcarbonyl optionally substituted with one or more halogen atoms, (12) C2-C6 alkoxycarbonyl optionally substituted with one or more halogen atoms, (13) C2-C6 alkylaminocarbonyl optionally substituted with one or more halogen atoms and (14) C3-C6 dialkylaminocarbonyl optionally substituted with one or more halogen atoms; C7-C9 phenylalkyl whose phenyl ring is optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) C1-C6 alkyl optionally substituted with one or more halogen atoms, (5) C1-C6 alkoxy optionally substituted with one or more halogen atoms, (6) C1-C6 alkylthio optionally substituted with one or more halogen atoms, (7) C1-C6 alkylsulfinyl optionally substituted with one or more halogen atoms, (8) C1-C6 alkylsulfonyl optionally substituted with one or more halogen atoms, (9) Cl-Cβ alkylamino optionally substituted with one or more halogen atoms, (10) C2-C6 dialkylamino optionally substituted with one or more halogen atoms, (11) C2-C6 alkylcarbonyl optionally substituted with one or more halogen atoms, (12) C2-C6 alkoxycarbonyl optionally substituted with one or more halogen atoms, (13) C2-C6 alkylaminocarbonyl optionally substituted with one or more halogen atoms and (14) C3-C6 dialkylaminocarbonyl optionally substituted with one or more halogen atoms; or C7-C9 pyridinylalkyl whose pyridine ring is optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) C1-C6 alkyl optionally substituted with one or more halogen atoms, (5) C1-C6 alkoxy optionally substituted with one or more halogen atoms, (6) C1-C6 alkylthio optionally substituted with one or more halogen atoms, (7) C1-C6 alkylsulfinyl optionally substituted with one or more halogen atoms, (8) C1-C6 alkylsulfonyl optionally substituted with one or more halogen atoms, (9) C1-C6 alkylamino optionally substituted with one or more halogen atoms, (10) C2-C6 dialkylamino optionally substituted with one or more halogen atoms, (11) C2-C6 alkylcarbonyl optionally substituted with one or more halogen atoms, (12) C2-C6 alkoxycarbonyl optionally substituted with one or more halogen atoms, (13) C2-C6 alkylaminocarbonyl optionally substituted with one or more halogen atoms and (14) C3-C6 dialkylaminocarbonyl optionally substituted with one or more halogen atoms;
R20ax, R20ay and R20az represent a halogen atom; cyano; nitro; thiocyanato; C1-C6 alkyl optionally substituted with one or more halogen atoms; C1-C6 alkoxy optionally substituted with one or more halogen atoms; C2-C6 cyanoalkyloxy; C2-C6 alkoxyalkyloxy optionally substituted with one or more halogen atoms; C2-C6 alkenyloxy optionally substituted with one or more halogen atoms; C2-C6 alkynyloxy optionally substituted with one or more halogen atoms; C1-C6 alkylthio optionally substituted with one or more halogen atoms; C1-C6 alkylsulfinyl optionally substituted with one or more halogen atoms; C1-C6 alkylsulfonyl optionally substituted with one or more halogen atoms; phenyl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) C1-C6 alkyl optionally substituted with one or more halogen atoms and (5) C1-C6 alkoxy optionally substituted with one or more halogen atoms;
5- to 6-membered heteroaryl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) C1-C6 alkyl optionally substituted with one or more halogen atoms and (5) C1-C6 alkoxy optionally substituted with one or more halogen atoms; or phenoxy optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) C1-C6 alkyl optionally substituted with one or more halogen atoms and (5) C1-C6 alkoxy optionally substituted with one or more halogen atoms.
The compound (10) can be produced, for example, according to the following scheme (1) . Scheme (1)
Figure imgf000130_0002
thiocyanate
Figure imgf000130_0001
In Scheme (I), A34, L1, Q', R2, R3 and R9a are as defined above .
Among the compound (10), a compound represented by the formula (10-i) :
Figure imgf000130_0003
wherein R2, R3 and R7 are as defined above, can be produced, for example, according to the following scheme (2) . Scheme (2)
Figure imgf000130_0004
In Scheme (2), R2, R3 and R7 are as defined above. The compound (17) can be produced, for example, according to the following Scheme (3) . Scheme (3)
Figure imgf000131_0001
In Scheme (3), R4 and n are as defined above.
The compounds (16), (18') and (20) can be produced, for example, according to the following Scheme (4). Scheme (4)
Figure imgf000132_0001
R1-a_L4 R1-a_|_4
R1-aOS(O)2OR1-a base etc.
Figure imgf000132_0002
In Scheme (4), R1"3, R4 and n are as defined above, and L4 represents a leaving group (e.g. a halogen atom, a methanesulfonyloxy group, a p-toluenesulfonyloxy etc.).
The compound (8) can be produced, for example, according to the process shown in the following Scheme (7) . Scheme (7)
R^0-C-J Hydrolysis HO-C-J /β) O O
1) Base
(LDA, n-BuLι etc.)
H-J *- (8j
2) CO2
1) Metal-halogen exchange
Br J (t-BuL i etc ) (8)
2) CO2
CH3 — J Oxidation (KMnO4 etc. )
(8)
Ox i dat i on H — c — j (KMnO4. Cr (VI) etc. )
Il »~ (8)
Figure imgf000133_0001
In Scheme (7), J is as defined above, R17 represents a methyl or an ethyl group, LDA represents lithium diisopropylamide, n-BuLi represents normal butyl lithium, and t-BuLi represents tertiary butyl lithium.
Among the compound (8), a compound represented by the formula (8-i)
Figure imgf000133_0002
wherein R13a, R14a, Xa, Ya, Za and p are as defined above, can be produced, for example, according to the process shown in the following Scheme (8) . Scheme (8) e e.. gg.. C nuuOu
base
Figure imgf000134_0001
Figure imgf000134_0002
Figure imgf000134_0003
( 8-i )
In Scheme (8), R13a, R14a, Xa, Ya, Za, p, LDA and n-BuLi are as defined above, and L5 represents a leaving group (e.g. a halogen atom, a methanesulfonyloxy group, a p- toluenesulfonyloxy group, a methylsulfonyl etc.).
Among the compound (8), a compound represented by the formula (8-ii) :
Figure imgf000134_0004
wherein R14a and p are as defined above, R18a, R18b, R18c and R18d, each, independently, represent a hydrogen atom, a halogen atom, cyano group, nitro group, C1-C6 alkyl optionally substituted with at least one halogen atom, Cl- C6 alkoxy optionally substituted with at least one halogen atom, C1-C6 alkylthio optionally substituted with at least one halogen atom, C1-C6 alkylsulfinyl optionally substituted with at least one halogen atom, or C1-C6 alkylsulfonyl optionally substituted with at least one halogen atom, can be produced, for example, according to the process shown in the following Scheme (9) . Scheme (9)
Figure imgf000135_0001
( 8-ii )
In Scheme (9), R14a, R18a, R18b, R18c, R18d, LDA and p are as defined above, and L6 represents a leaving group (e.g. a halogen atom, a methylsulfonyl etc.).
Among the compound (8), a compound represented by the formula (8-iii) : )
Figure imgf000136_0001
wherein R18a, R18b, R18c, R18d and R18e independently represent a hydrogen atom, a halogen atom, cyano group, nitro group, C1-C6 alkyl optionally substituted with at least one halogen atom, Cl-Cβ alkoxy optionally substituted with at least one halogen atom, Cl-Cβ alkylthio optionally- substituted with at least one halogen atom, C1-C6 alkylsulfinyl optionally substituted with at least one halogen atom, or C1-C6 alkylsulfonyl optionally substituted with at least one halogen atom, can be produced, for example, according to the process shown in the following Scheme (10) .
Scheme (10)
Figure imgf000137_0001
( 8-iii )
In Scheme (10), R18a, R18b, R18c, R18d and R18e are as defined above .
Among the compound (8), a compound represented by the formula (8-iv) :
Figure imgf000137_0002
wherein X18 represents -N=, or -CR18e=; R18a, R18b, R18c, R18d and R18e are as defined above, and R148"1 represents C1-C6 alkyl optionally substituted with at least one halogen atom, can be produced, for example, according to the process shown in the following Scheme (11) . Scheme (11)
Figure imgf000138_0001
(8-iv)
In Scheme (11), R14aΛ R17, R18a, R18b, R18c, R18d and X18 are as defined above, and R20 represents a methyl or an ethyl group.
Among the compound (8), a compound represented by the formula (8-vii) :
Figure imgf000138_0002
wherein R13b, R14b, Xb, Yb, Zb and q are as defined above, can be produced, for example, according to the process shown in the following Scheme (14) . Scheme (14)
Figure imgf000139_0001
Hydrolysis
Figure imgf000139_0002
(8-vii)
In Scheme (14), R13b, R14b, R17, Xb, Yb, Zb, L5 and q are as defined above.
Among the compound (8), a compound represented by the formula (8-viii) and the formula (8-ix):
Figure imgf000139_0003
( 8-viii) ( 8-'x)
[wherein R13b is as defined above, X19 represents -N=, or -CR19e=, R19a, R19b, R19c, R19d and R19e, each, independently, represent a hydrogen atom, a halogen atom, cyano group, a nitro group, C1-C6 alkyl optionally substituted with at least one halogen atom, C1-C6 alkoxy optionally substituted with at least one halogen atom, C1-C6 alkylthio optionally substituted with at least one halogen atom, C1-C6 alkylsulfinyl optionally substituted with at least one halogen atom, or C1-C6 alkylsulfonyl optionally substituted with at least one halogen atom] can be produced, for example, according to the process shown in the following Scheme (15) . Scheme (15)
Figure imgf000141_0001
( 8-viii) (8-ix)
Hydrolysis Hydrolysis
Figure imgf000141_0002
( 8-viu) ( 8-ix)
In Scheme (15), R13b, R17, R19a, R19b, R19c, R19d, L5 and X19 are as defined above.
Among the compound (7), a compound represented by the formula (7-i) :
Figure imgf000142_0001
wherein L2 and J are as defined above, can be produced, for example, according to the process shown in the following Scheme (16) . Scheme (16)
HO
Figure imgf000142_0002
(8) ( 7-i )
In Scheme (16), L2 and J are as defined above.
Among the compound (7), a compound represented by the formula (7-ii) :
L2—C-J
Il (7-ii) S wherein L2 and J are as defined above, can be produced, for example, according to the process shown in the following scheme ( 17 ) . Scheme (17)
aaggeenntt
Figure imgf000142_0003
2) CS2
In Scheme (17), L2 and J are as defined above, LDA represents lithium diisopropylamide, n-BuLi represents normal butyl lithium, and t-BuLi represents tertiary butyl lithium.
Among the compound (8), a compound represented by the formula (8-v) :
Figure imgf000143_0001
wherein R18a, R18b, R18c, R18d and X18 are as defined above, and R14ax, R14ay and X14az independently represent a hydrogen atom, a halogen atom, cyano group, C1-C6 alkyl optionally substituted with at least one halogen atom, C1-C6 alkoxy optionally substituted with at least one halogen atom, Cl- C6 alkylthio optionally substituted with at least one halogen atom, C1-C6 alkylsulfinyl optionally substituted with at least one halogen atom, or C1-C6 alkylsulfonyl optionally substituted with at least one halogen atom, can be produced, for example, according to the process shown in the following Scheme (18) . Scheme (18)
Figure imgf000144_0001
(21) ( 8-v)
In Scheme (18) , R18a, R18b, R18c, R18d, X18, R14ax, R14ay and X14az are as defined above.
The compounds (21) in scheme (18) can be produced, for example, according to the process shown in the following Scheme (19) . Scheme (19)
Figure imgf000145_0001
In Scheme (19) , R18a, R18b, R18c, R18d, R18e, X18, R14ax, R14ay,
X14az and L6 are as defined above.
Among the compounds (21) in scheme (18), a compound represented by the formula (21-i), the formula (21-ii), and the formula (21-iii):
Figure imgf000146_0001
(21-i) (21-ii) (21-iii) wherein R18a, R18b, R18c, R18d and X18 are as defined above, and halo(x) and halo(y) independently represent a halogen atom, can be produced, for example, according to the process shown in the following Scheme (20) . Scheme (20)
Figure imgf000146_0002
(21-iii)
In Scheme (20) , R18a, R18b, R18c, R18d, X18, halo(x) and halo (y) are as defined above. Among the compound (8), a compound represented by the formula (8-vi) :
Figure imgf000147_0001
wherein R18a, R18b, R18c, R18d and X18 are as defined above, £-4ay-i represents a hydrogen atom or a halogen atom, R30 represents C1-C6 alkyl optionally substituted with at least one halogen atom, and r represents an integer of 0 to 2, can be produced, for example, according to the process shown in the following Scheme (21) . Scheme (21)
Figure imgf000148_0001
(21)
((RR1144aaxx = R14az=H,
R14ay = Horhalo)
Figure imgf000148_0002
Oxidation (KMnO4, etc.)
Figure imgf000148_0003
( 8-vi) ( 8-vi) (r = 0) (r=lor2)
In Scheme (21), R18a, R18b, R18c, R18d, X18 , R14^"1 , R30, r and L4 are as defined above.
The specific examples of the present compound are summarized in the following compounds 1 to 277.
Figure imgf000149_0001
Compound 1 :
Compounds of formula IA wherein R2, R3, M, R19a, R20aγ and X corresponds to a row in Table A, and E substituted with (R4)n is:
Figure imgf000149_0002
Compund 2 :
Compounds of formula IA wherein R2, R3, M, R19a, R20aγ and X corresponds to a row in Table A, and E substituted with
(R4 is :
Figure imgf000149_0003
Compund 3 :
Compounds of formula IA wherein R2, R3, M, R19a, R20ay and X corresponds to a row in Table A, and E substituted with
(R4)n is:
Figure imgf000149_0004
Compund 4 :
Compounds of formula IA wherein R2, R3, M, R19a, R20ay and X corresponds to a row in Table A, and E substituted with
(R4)n is:
Figure imgf000150_0001
Compund 5 :
Compounds of formula IA wherein R2, R3, M, R19a, R20ay and X corresponds to a row in Table A, and E substituted with
(R4)n is:
Figure imgf000150_0002
Compund 6 :
Compounds of formula IA wherein R2, R3, M, R19a, R20ay and X corresponds to a row in Table A, and E substituted with
(R4 is
Figure imgf000150_0003
Compund 7 :
Compounds of formula IA wherein R2, R3, M, R19a, R20ay and X corresponds to a row in Table A, and E substituted with
(R4 is
Figure imgf000150_0004
Compund 8 : Compounds of formula IA wherein R2, R3, M, R19a, R20aγ and X corresponds to a row in Table A, and E substituted with
(R4 is
Figure imgf000151_0001
Compund 9 :
Compounds of formula IA wherein R2, R3, M, R19a, R20ay and X corresponds to a row in Table A, and E substituted with
(R4)n xs :
Figure imgf000151_0002
Compund 10:
Compounds of formula IA wherein R2, R3, M, R19a, R20aγ and X corresponds to a row in Table A, and E substituted with
(R4)n is:
Figure imgf000151_0003
Compund 11:
Compounds of formula IA wherein R2, R3, M, R19a, R20ay and X corresponds to a row in Table A, and E substituted with
(R4)n is:
Figure imgf000151_0004
Compund 12: Compounds of formula IA wherein R2, R3, M, R19a, R20ay and X corresponds to a row in Table A, and E substituted with
(R4)n is:
Figure imgf000152_0001
Compund 13:
Compounds of formula IA wherein R2, R3, M, R19a, R20ay and X corresponds to a row in Table A, and E substituted with
(R4 is :
Figure imgf000152_0002
Compund 14:
Compounds of formula IA wherein R2, R3, M, R19a, R20ay and X corresponds to a row in Table A, and E substituted with
(R4)n is:
Figure imgf000152_0003
Compund 15:
Compounds of formula IA wherein R2, R3, M, R19a, R20ay and X corresponds to a row in Table A, and E substituted with
(R4 ) n is :
Figure imgf000152_0004
Compund 16 :
Compounds of formula IA wherein R2, R3, M, R19a, R20ay and X corresponds to a row in Table A, and E substituted with (R4)n is:
Figure imgf000153_0001
Compund 17 : Compounds of formula IA wherein R2, R3, M, R19a, R20aγ and X corresponds to a row in Table A, and E substituted with
(R4 is :
Figure imgf000153_0002
Compund 18: Compounds of formula IA wherein R2, R3, M, R19a, R20aγ and X corresponds to a row in Table A, and E substituted with
(R4)n is:
Figure imgf000153_0003
Compund 19: Compounds of formula IA wherein R2, R3, M, R19a, R20ay and X corresponds to a row in Table A, and E substituted with
(R" is :
Figure imgf000153_0004
Compund 20: Compounds of formula IA wherein R2, R3, M, R19a, R20ay and X corresponds to a row in Table A, and E substituted with
( R' I S
Figure imgf000154_0001
Compund 21 : Compounds of formula IA wherein R2 , R3, M, R19a, R20ay and X corresponds to a row in Table A, and E substituted with
( R4 I S
Figure imgf000154_0002
Compund 22 : Compounds of formula IA wherein R2, R3, M, R19a, R20ay and X corresponds to a row in Table A, and E substituted with
(R IS
Figure imgf000154_0003
Compund 23: Compounds of formula IA wherein R2, R3, M, R19a, R2Oay and X corresponds to a row in Table A, and E substituted with
(R4)π is:
Figure imgf000154_0004
Compund 24: Compounds of formula IA wherein R2, R3, M, R19a, R20ay and X corresponds to a row in Table A, and E substituted with (R4)n is:
Figure imgf000155_0001
Compund 25:
Compounds of formula IA wherein R2, R3, M, R19a, R2Oay and X corresponds to a row in Table A, and E substituted with (R4)n is:
Figure imgf000155_0002
Compund 26 :
Compounds of formula IA wherein R2 , R3 , M, R19a, R20ay and X corresponds to a row in Table A, and E substituted with
( R4 ) n i s :
Figure imgf000155_0003
Compund 27 :
Compounds of formula IA wherein R2, R3, M, R19a, R20ay and X corresponds to a row in Table A, and E substituted with
(R4)n is:
Figure imgf000155_0004
Compund 28:
Compounds of formula IA wherein R2, R3, M, R19a, R20ay and X corresponds to a row in Table A, and E substituted with ( R* i s
Figure imgf000156_0001
Compund 29 :
Compounds of formula IA wherein R2, R3, M, R19a, R20ay and X corresponds to a row in Table A, and E substituted with
(R4 ) n is :
Figure imgf000156_0002
Compund 30 :
Compounds of formula IA wherein R2, R3, M, R19a, R2Oay and X corresponds to a row in Table A, and E substituted with
(R4)n is:
Figure imgf000156_0003
Compund 31:
Compounds of formula IA wherein R2, R3, M, R19a, R20ay and X corresponds to a row in Table A, and E substituted with
(R4)n is:
Figure imgf000156_0004
Compund 32 :
Compounds of formula IA wherein R2, R3, M, R19a, R20ay and X corresponds to a row in Table A, and E substituted with (R4)n is:
Figure imgf000157_0001
Compund 33:
Compounds of formula IA wherein R2, R3, M, R19a, R20aγ and X corresponds to a row in Table A, and E substituted with (R4)n is:
Figure imgf000157_0002
Compund 34 :
Compounds of formula IA wherein R2, R3, M, R19a, R20ay and X corresponds to a row in Table A, and E substituted with
(R4)n is:
Figure imgf000157_0003
Compund 35:
Compounds of formula IA wherein R2, R3, M, R19a, R20aγ and X corresponds to a row in Table A, and E substituted with
(R4)n IS
Figure imgf000157_0004
Compund 36:
Compounds of formula IA wherein R2, R3, M, R19a, R20ay and X corresponds to a row in Table A, and E substituted with (R4)n is:
Figure imgf000158_0001
Compund 37 :
Compounds of formula IA wherein R2, R3, M, R19a, R20ay and X corresponds to a row in Table A, and E substituted with
(R4 is
Figure imgf000158_0002
Compund 38:
Compounds of formula IA wherein R2, R3, M, R19a, R20ay and X corresponds to a row in Table A, and E substituted with
(R i s
Figure imgf000158_0003
Compund 39 :
Compounds of formula IA wherein R2, R3, M, R19a, R2Oay and X corresponds to a row in Table A, and E substituted with (R4)n is:
Figure imgf000158_0004
Compund 40 :
Compounds of formula IA wherein R2, R3, M, R19a, R20ay and X corresponds to a row in Table A, and E substituted with (R4)n is:
Figure imgf000159_0001
Compund 41:
Compounds of formula IA wherein R2, R3, M, R19a, R2Oay and X corresponds to a row in Table A, and E substituted with
(R4 is
Figure imgf000159_0002
Compund 42:
Compounds of formula IA wherein R2, R3, M, R19a, R20ay and X corresponds to a row in Table A, and E substituted with
(R' is
Figure imgf000159_0003
Compund 43:
Compounds of formula IA wherein R2, R3, M, R19a, R20ay and X corresponds to a row in Table A, and E substituted with
(R* is :
Figure imgf000159_0004
Compund 44 :
Compounds of formula IA wherein R2, R3, M, R19a, R20ay and X corresponds to a row in Table A, and E substituted with (R4)n is:
Figure imgf000160_0001
Compund 45:
Compounds of formula IA wherein R2, R3, M, R19a, R20aγ and X corresponds to a row in Table A, and E substituted with
(Rq is :
Figure imgf000160_0002
Compund 46:
Compounds of formula IA wherein R2, R3, M, R19a, R20ay and X corresponds to a row in Table A, and E substituted with
( R4 xs
Figure imgf000160_0003
Compund 47 :
Compounds of formula IA wherein R2, R3, M, R19a, R20aγ and X corresponds to a row in Table A, and E substituted with (R4)n is:
Figure imgf000160_0004
Compund 48:
Compounds of formula IA wherein R2, R3, M, R19a, R2Oay and X corresponds to a row in Table A, and E substituted with (R4)n is:
Figure imgf000161_0001
Compund 49 :
Compounds of formula IA wherein R2, R3, M, R19a, R20aγ and X corresponds to a row in Table A, and E substituted with
(R' is
Figure imgf000161_0002
Compund 50:
Compounds of formula IA wherein R2, R3, M, R19a, R20ay and X corresponds to a row in Table A, and E substituted with
[R* is :
Figure imgf000161_0003
Compund 51:
Compounds of formula IA wherein R2, R3, M, R19a, R20ay and X corresponds to a row in Table A, and E substituted with
(R4)n is :
Figure imgf000161_0004
Compund 52 :
Compounds of formula IA wherein R2, R3, M, R19a, R20ay and X corresponds to a row in Table A, and E substituted with (R4)n is:
Figure imgf000162_0001
Compund 53:
Compounds of formula IA wherein R2, R3, M, R19a, R20aγ and X corresponds to a row in Table A, and E substituted with
(R4)n is
Figure imgf000162_0002
Compund 54 :
Compounds of formula IA wherein R2, R3, M, R19a, R20aγ and X corresponds to a row in Table A, and E substituted with
( R' i s
Figure imgf000162_0003
Compund 55 :
Compounds of formula IA wherein R2, R3, M, R19a, R20ay and X corresponds to a row in Table A, and E substituted with
(R4 is
Figure imgf000162_0004
Compund 56:
Compounds of formula IA wherein R2, R3, M, R19a, R20ay and X corresponds to a row in Table A, and E substituted with (R4)n is:
Figure imgf000163_0001
Compund 57 :
Compounds of formula IA wherein R2, R3, M, R19a, R20ay and X corresponds to a row in Table A, and E substituted with (R4)n is:
Figure imgf000163_0002
Compund 58:
Compounds of formula IA wherein R2, R3, M, R19a, R20ay and X corresponds to a row in Table A, and E substituted with
(R' xs :
Figure imgf000163_0003
Compund 59:
Compounds of formula IA wherein R2, R3, M, R19a, R20ay and X corresponds to a row in Table A, and E substituted with
(R4 is
Figure imgf000163_0004
Compund 60:
Compounds of formula IA wherein R2, R3, M, R19a, R20ay and X corresponds to a row in Table A, and E substituted with (R4)n is:
Figure imgf000164_0001
Compund 61:
Compounds of formula IA wherein R2, R3, M, R19a, R2Oay and X corresponds to a row in Table A, and E substituted with
(R' is
Compund 62 : ,i
Compounds of formula IA wherein R2, R3, M, R19a, R20aγ and X corresponds to a row in Table A, and E substituted with
(R* is
Figure imgf000164_0002
Compund 63 :
Compounds of formula IA wherein R2, R3, M, R19a, R20aγ and X corresponds to a row in Table A, and E substituted with (R4)n is:
Figure imgf000164_0003
Compund 64 :
Compounds of formula IA wherein R2, R3, M, R19a, R20ay and X corresponds to a row in Table A, and E substituted with (R4)n is:
Figure imgf000165_0001
Table A
Figure imgf000165_0002
Figure imgf000166_0001
Figure imgf000167_0001
Figure imgf000168_0001
Figure imgf000169_0001
Figure imgf000170_0001
Figure imgf000171_0001
Figure imgf000172_0001
Figure imgf000173_0001
Figure imgf000174_0001
Figure imgf000175_0001
Figure imgf000176_0001
Figure imgf000177_0001
Figure imgf000178_0001
Figure imgf000179_0001
Figure imgf000180_0001
Figure imgf000181_0001
Figure imgf000182_0001
Figure imgf000183_0001
Figure imgf000184_0001
Figure imgf000185_0001
Figure imgf000186_0001
Figure imgf000187_0001
Figure imgf000188_0001
Figure imgf000189_0001
Figure imgf000190_0001
Figure imgf000191_0001
Figure imgf000192_0001
Figure imgf000193_0001
Figure imgf000194_0001
Figure imgf000195_0001
Figure imgf000196_0001
Figure imgf000197_0001
Figure imgf000198_0001
Figure imgf000199_0001
Figure imgf000200_0001
Figure imgf000201_0001
Figure imgf000202_0001
Figure imgf000203_0001
Figure imgf000204_0001
Figure imgf000205_0001
Figure imgf000206_0001
Figure imgf000207_0001
Figure imgf000208_0001
Figure imgf000209_0001
Figure imgf000210_0001
Figure imgf000211_0001
Figure imgf000212_0001
Figure imgf000213_0001
Figure imgf000214_0001
Figure imgf000215_0001
Figure imgf000216_0001
Figure imgf000217_0001
Figure imgf000218_0001
Figure imgf000219_0001
Figure imgf000220_0001
Figure imgf000221_0001
Figure imgf000222_0001
Figure imgf000223_0001
Figure imgf000224_0001
Figure imgf000225_0001
Figure imgf000226_0001
Figure imgf000227_0001
Figure imgf000228_0001
Figure imgf000229_0001
Figure imgf000230_0001
Figure imgf000231_0001
Figure imgf000232_0001
Figure imgf000233_0001
Figure imgf000234_0001
Figure imgf000235_0001
Figure imgf000236_0001
Figure imgf000237_0001
Figure imgf000238_0001
Figure imgf000239_0001
Figure imgf000240_0001
Figure imgf000241_0001
Figure imgf000242_0001
Figure imgf000243_0001
Figure imgf000244_0001
Figure imgf000245_0001
Figure imgf000246_0001
Figure imgf000247_0001
Figure imgf000248_0001
Figure imgf000249_0001
Figure imgf000250_0001
Figure imgf000251_0001
Figure imgf000252_0001
Figure imgf000253_0001
Figure imgf000255_0001
Figure imgf000256_0001
Figure imgf000257_0001
Figure imgf000258_0001
Figure imgf000259_0001
Figure imgf000260_0001
Figure imgf000261_0001
Figure imgf000262_0001
Figure imgf000263_0001
Figure imgf000264_0001
Figure imgf000265_0001
Figure imgf000266_0001
Figure imgf000267_0001
Figure imgf000268_0001
Figure imgf000269_0001
Figure imgf000270_0001
Figure imgf000271_0001
Figure imgf000272_0001
Figure imgf000273_0001
Figure imgf000274_0001
Figure imgf000275_0001
Figure imgf000276_0001
Figure imgf000277_0001
Figure imgf000278_0001
Figure imgf000279_0001
Figure imgf000280_0001
Figure imgf000281_0001
Figure imgf000282_0001
Figure imgf000283_0001
Figure imgf000284_0001
Figure imgf000285_0001
Figure imgf000286_0001
Figure imgf000287_0001
Figure imgf000288_0001
Figure imgf000289_0001
Figure imgf000290_0004
Figure imgf000290_0001
Compund 65:
Compounds of formula 2A wherein Rz, RJ, M and R^ corresponds to a row in Table B, and E substituted with (R4)n is:
Figure imgf000290_0002
Compund 66:
Compounds of formula 2A wherein Rz, RJ, M and Rz corresponds to a row in Table B, and E substituted with
:R4)n is:
Figure imgf000290_0003
Compund 67 :
Compounds of formula 2A wherein R2, R3, M and R20ay corresponds to a row in Table B, and E substituted with
(R4 is
Figure imgf000291_0001
Compund 68 :
Compounds of formula 2A wherein Rz, RJ, M and Rz corresponds to a row in Table B, and E substituted with
(R4 is
Figure imgf000291_0002
Compund 69:
Compounds of formula 2A wherein R^, RJ, M and R^ corresponds to a row in Table B, and E substituted with
(R4)π is :
Figure imgf000291_0003
Compund 70:
Compounds of formula 2A wherein R2, R3, M and R20ay corresponds to a row in Table B, and E substituted with
(R4)n is:
Figure imgf000291_0004
Compund 71: Compounds of formula 2A wherein R2, R3, M and R20ay corresponds to a row in Table B, and E substituted with
(R4)n is:
Figure imgf000292_0001
Compund 72:
Compounds of formula 2A wherein Rz, RJ, M and R^ corresponds to a row in Table B, and E substituted with
(R' is
Figure imgf000292_0002
Compund 73:
Compounds of formula 2A wherein R^, RJ, M and Rz corresponds to a row in Table B, and E substituted with (R4)n is:
Figure imgf000292_0003
Compund 74:
Compounds of formula 2A wherein R2, R3, M and R20ay corresponds to a row in Table B, and E substituted with
(R4 is
Figure imgf000292_0004
Compund 75: Compounds of formula 2A wherein R2, R3, M and R20ay corresponds to a row in Table B, and E substituted with
(R4)n is:
Figure imgf000293_0001
Compund 76 :
Compounds of formula 2A wherein R2, R3, M and R20ay corresponds to a row in Table B, and E substituted with (R4)n is:
Figure imgf000293_0002
Compund 77:
Compounds of formula 2A wherein R , R , M and R203^ corresponds to a row in Table B, and E substituted with
(R4)n is:
Figure imgf000293_0003
Compund 78:
Compounds of formula 2A wherein R^, R"5, M and R^ corresponds to a row in Table B, and E substituted with
(R4)n is:
Figure imgf000293_0004
Compund 79:
Compounds of formula 2A wherein R2, R3, M and R203^ corresponds to a row in Table B, and E substituted with
(R4)n is:
Figure imgf000294_0001
Compund 80 :
Compounds of formula 2A wherein R2, R3, M and R20ay corresponds to a row in Table B, and E substituted with
(R" IS
Figure imgf000294_0002
Compund 81 : Compounds of formula 2A wherein R^, RJ, M and R^ corresponds to a row in Table B, and E substituted with
(R4)n is :
Figure imgf000294_0003
Compund 82: Compounds of formula 2A wherein Rz, RJ, M and R^ corresponds to a row in Table B, and E substituted with
(R4)n is:
Figure imgf000294_0004
Compund 83: Compounds of formula 2A wherein R^, RJ, M and R^ corresponds to a row in Table B, and E substituted with
(Rq IS
Figure imgf000295_0001
Compund 84: Compounds of formula 2A wherein R2, R3, M and R20ay corresponds to a row in Table B, and E substituted with
(R4 IS
Figure imgf000295_0002
Compund 85: Compounds of formula 2A wherein R2, R3, M and R203^ corresponds to a row in Table B, and E substituted with
(R4)n is:
Figure imgf000295_0003
Compund 86 : Compounds of formula 2A wherein R2, R3, M and R20ay corresponds to a row in Table B, and E substituted with
(R4)n is:
Figure imgf000295_0004
Compund 87: Compounds of formula 2A wherein R2, R3, M and R20ay corresponds to a row in Table B, and E substituted with (R' is :
Figure imgf000296_0001
Compund 88 :
Compounds of formula 2A wherein R2, R3, M and R20ay corresponds to a row in Table B, and E substituted with
(R4 is
Figure imgf000296_0002
Compund 89:
Compounds of formula 2A wherein Rz, RJ, M and R^ corresponds to a row in Table B, and E substituted with (R4)n is:
Figure imgf000296_0003
Compund 90:
Compounds of formula 2A wherein R2, R3, M and R203^ corresponds to a row in Table B, and E substituted with
(R4)n is:
Figure imgf000296_0004
Compund 91:
Compounds of formula 2A wherein R^, RJ, M and R^ corresponds to a row in Table B, and E substituted with (R4 is
Figure imgf000297_0001
Compund 92 :
Compounds of formula 2A wherein Rz, RJ, M and R^ corresponds to a row in Table B, and E substituted with (R4)n is:
Figure imgf000297_0002
Compund 93 :
Compounds of formula 2A wherein R , R , M and R203^ corresponds to a row in Table B , and E substituted with
( R4 ) n i s :
Figure imgf000297_0003
Compund 94 :
Compounds of formula 2A wherein R2, R3, M and R20ay corresponds to a row in Table B, and E substituted with (R4)n is:
Figure imgf000297_0004
Compund 95:
Compounds of formula 2A wherein R*, RJ, M and R^ corresponds to a row in Table B, and E substituted with (R4)π is:
Figure imgf000298_0001
Compund 96:
Compounds of formula 2A wherein R2, R3, M and R20ay corresponds to a row in Table B, and E substituted with
(R4 is
Figure imgf000298_0002
Compund 97 :
Compounds of formula 2A wherein Rz, RJ, M and R^ corresponds to a row in Table B, and E substituted with
(R' is
Figure imgf000298_0003
Compund 98:
Compounds of formula 2A wherein Rz, RJ, M and R^ corresponds to a row in Table B, and E substituted with
(Rq is
Figure imgf000298_0004
Compund 99:
Compounds of formula 2A wherein R2, R3, M and R20ay corresponds to a row in Table B, and E substituted with (R4)n is:
Figure imgf000299_0001
Compund 100 :
Compounds of formula 2A wherein R2, R3, M and R20ay corresponds to a row in Table B, and E substituted with
(R4)n is:
Figure imgf000299_0002
Compund 101:
Compounds of formula 2A wherein Rz, RJ, M and Rz corresponds to a row in Table B, and E substituted with
( R4 ) n is :
Figure imgf000299_0003
Compund 102 :
Compounds of formula 2A wherein R2, R3, M and R20ay corresponds to a row in Table B, and E substituted with
( R4 i s
Figure imgf000299_0004
Compund 103 :
Compounds of formula 2A wherein R2, R3, M and R20ay corresponds to a row in Table B, and E substituted with (R4)n is:
Figure imgf000300_0001
Compund 104:
Compounds of formula 2A wherein R2, R3, M and R20ay corresponds to a row in Table B, and E substituted with is :
Compund 105:
Compounds of formula 2A wherein R^, RJ, M and Rz corresponds to a row in Table B, and E substituted with
(R4)n IS
Figure imgf000300_0003
Compund 106:
Compounds of formula 2A wherein Rz, RJ, M and R^ corresponds to a row in Table B, and E substituted with (R4)n is:
Figure imgf000300_0004
Compund 107:
Compounds of formula 2A wherein R2, R3, M and R20ay corresponds to a row in Table B, and E substituted with (R4)n is:
Figure imgf000301_0001
Compund 108 :
Compounds of formula 2A wherein R^, RJ, M and R^ corresponds to a row in Table B, and E substituted with
( R4 is :
Figure imgf000301_0002
Compund 109 :
Compounds of formula 2A wherein R2, R3, M and R20ay corresponds to a row in Table B, and E substituted with
(R4)n is:
Figure imgf000301_0003
Compund 110:
Compounds of formula 2A wherein R2, R3, M and R20ay corresponds to a row in Table B, and E substituted with
(R4 i s
Figure imgf000301_0004
Compund 111 :
Compounds of formula 2A wherein R2, R3, M and R20ay corresponds to a row in Table B, and E substituted with (R4)n is:
Figure imgf000302_0001
Compund 112:
Compounds of formula 2A wherein R2, R3, M and R203^ corresponds to a row in Table B, and E substituted with
( R4 i s
Figure imgf000302_0002
Compund 113 :
Compounds of formula 2A wherein Rz, RJ, M and R^ corresponds to a row in Table B, and E substituted with
(R4)n is :
Figure imgf000302_0003
Compund 114:
Compounds of formula 2A wherein Rz, RJ, M and R^ corresponds to a row in Table B, and E substituted with (R4)n is:
Figure imgf000302_0004
Compund 115:
Compounds of formula 2A wherein R2, R3, M and R20ay corresponds to a row in Table B, and E substituted with (R4)n is:
Figure imgf000303_0001
Compund 116:
Compounds of formula 2A wherein R2, R3, M and R20ay corresponds to a row in Table B, and E substituted with
(Rq is :
Figure imgf000303_0002
Compund 117:
Compounds of formula 2A wherein Rz, RJ, M and R^ corresponds to a row in Table B, and E substituted with
(R4)n IS
Figure imgf000303_0003
Compund 118:
Compounds of formula 2A wherein R2, R3, M and R20ay corresponds to a row in Table B, and E substituted with ( R4 ) n is :
Figure imgf000303_0004
Compund 119 :
Compounds of formula 2A wherein R2, R3, M and R20ay corresponds to a row in Table B, and E substituted with (R4)n is:
Figure imgf000304_0001
Compund 120:
Compounds of formula 2A wherein R2, R3, M and R20ay corresponds to a row in Table B, and E substituted with
(R4 is
Figure imgf000304_0002
Compund 121:
Compounds of formula 2A wherein R2, R3, M and R20ay corresponds to a row in Table B, and E substituted with
(R*) n is:
Figure imgf000304_0003
Compund 122:
Compounds of formula 2A wherein R^, RJ, M and R^ corresponds to a row in Table B, and E substituted with
(R4 is
Figure imgf000304_0004
Compund 123:
Compounds of formula 2A wherein R^, RJ, M and R^ corresponds to a row in Table B, and E substituted with (R4)n is:
Figure imgf000305_0001
Compund 124 :
Compounds of formula 2A wherein R2, R3, M and R203^ corresponds to a row in Table B, and E substituted with
(R4 is
Figure imgf000305_0002
Compund 125:
C Compounds of formula 2A wherein R^, RJ, M and R^ corresponds to a row in Table B, and E substituted with
[R' is :
Compund 126: ,i
Compounds of formula 2A wherein R2, R3, M and R20ay corresponds to a row in Table B, and E substituted with ( R4 ) n is :
Figure imgf000305_0003
Compund 127 :
Compounds of formula 2A wherein R2, R3, M and R20ay corresponds to a row in Table B, and E substituted with (R4)n is:
Figure imgf000306_0001
Compund 128:
Compounds of formula 2A wherein R , R , M and R20ay corresponds to a row in Table B, and E substituted with (R4)n is:
Figure imgf000306_0002
Table B
Figure imgf000306_0003
Figure imgf000307_0001
Figure imgf000308_0002
Figure imgf000308_0001
Compund 129: Compounds of formula 3A wherein R , R3, M and R corresponds to a row in Table C, and E substituted with
(Rq IS
Figure imgf000309_0001
Compund 130:
Compounds of formula 3A wherein R2, R3, M and R20ax corresponds to a row in Table C, and E substituted with
(R4 IS
Figure imgf000309_0002
Compund 131:
Compounds of formula 3A wherein R , R3, M and R corresponds to a row in Table C, and E substituted with
(R4)n is:
Figure imgf000309_0003
Compund 132:
Compounds of formula 3A wherein R2, R3, M and R20ax corresponds to a row in Table C, and E substituted with
(R4)n is:
Figure imgf000309_0004
Compund 133:
Compounds of formula 3A wherein R2, R3, M and R20ax corresponds to a row in Table C, and E substituted with
(R4)n is:
Figure imgf000310_0001
Compund 134:
Compounds of formula 3A wherein R2, R3, M and R20ax corresponds to a row in Table C, and E substituted with
(R* is :
Figure imgf000310_0002
Compund 135: Compounds of formula 3A wherein R2, R3, M and R20ax corresponds to a row in Table C, and E substituted with
(R* IS
Figure imgf000310_0003
Compund 136: Compounds of formula 3A wherein R2, R3, M and R20ax corresponds to a row in Table C, and E substituted with
(R4)n is:
Figure imgf000310_0004
Compund 137 : Compounds of formula 3A wherein R2, R3, M and R20ax corresponds to a row in Table C, and E substituted with
(R4 is :
Figure imgf000311_0001
Compund 138:
Compounds of formula 3A wherein R2, R3, M and R20ax corresponds to a row in Table C, and E substituted with
(R4 IS
Figure imgf000311_0002
Compund 139: Compounds of formula 3A wherein R2, R3, M and R20ax corresponds to a row in Table C, and E substituted with
[R* is :
Figure imgf000311_0003
Compund 140: Compounds of formula 3A wherein Rz, RJ, M and R^ corresponds to a row in Table C, and E substituted with
(R4)π xs :
Figure imgf000311_0004
Compund 141: Compounds of formula 3A wherein R2, R3, M and R20ax corresponds to a row in Table C, and E substituted with (R4 is :
Figure imgf000312_0001
Compund 142:
Compounds of formula 3A wherein R2, R3, M and R20ax corresponds to a row in Table C, and E substituted with
[R" is
Figure imgf000312_0002
Compund 143:
Compounds of formula 3A wherein R2, R3, M and R20ax corresponds to a row in Table C, and E substituted with
(R4 is
Figure imgf000312_0003
Compund 144 :
Compounds of formula 3A wherein R2, R3, M and R20ax corresponds to a row in Table C, and E substituted with
(R4)n is:
Figure imgf000312_0004
Compund 145:
Compounds of formula 3A wherein R2, R3, M and R20ax corresponds to a row in Table C, and E substituted with (R4 is :
Figure imgf000313_0001
Compund 146:
Compounds of formula 3A wherein Rz, RJ, M and R^ corresponds to a row in Table C, and E substituted with
[R4)n is :
Figure imgf000313_0002
Compund 147:
Compounds of formula 3A wherein Rz, RJ, M and R^ corresponds to a row in Table C, and E substituted with
(R4 is :
Figure imgf000313_0003
Compund 148:
Compounds of formula 3A wherein R2, R3, M and R20ax corresponds to a row in Table C, and E substituted with
(R4)n is:
Figure imgf000313_0004
Compund 149:
Compounds of formula 3A wherein R2, R3, M and R20ax corresponds to a row in Table C, and E substituted with (R4)n is:
Figure imgf000314_0001
Compund 150:
Compounds of formula 3A wherein R2, R3, M and R20ax corresponds to a row in Table C, and E substituted with
(R4 is :
Figure imgf000314_0002
Compund 151:
Compounds of formula 3A wherein R2, R3, M and R20ax corresponds to a row in Table C, and E substituted with
(R" is :
Figure imgf000314_0003
Compund 152:
Compounds of formula 3A wherein R2, R3, M and R20ax corresponds to a row in Table C, and E substituted with (R4)n is:
Figure imgf000314_0004
Compund 153:
Compounds of formula 3A wherein R2, R3, M and R2Oax corresponds to a row in Table C, and E substituted with (R4)n is:
Figure imgf000315_0001
Compund 154 :
Compounds of formula 3A wherein R2, R3, M and R20ax corresponds to a row in Table C, and E substituted with
(R' is :
Figure imgf000315_0002
Compund 155:
Compounds of formula 3A wherein R , R3, M and R corresponds to a row in Table C, and E substituted with
(R4)n IS
Figure imgf000315_0003
Compund 156:
Compounds of formula 3A wherein R2, R3, M and R20ax corresponds to a row in Table C, and E substituted with
(R* is
Figure imgf000315_0004
Compund 157:
Compounds of formula 3A wherein R2, R3, M and R20ax corresponds to a row in Table C, and E substituted with (R4)n is:
Figure imgf000316_0001
Compund 158 :
Compounds of formula 3A wherein R2, R3, M and R20ax corresponds to a row in Table C, and E substituted with (R4)n is:
Figure imgf000316_0002
Compund 159:
Compounds of formula 3A wherein R2, R3, M and R20ax corresponds to a row in Table C, and E substituted with
(R4 is
Figure imgf000316_0003
Compund 160:
Compounds of formula 3A wherein R2, R3, M and R20ax corresponds to a row in Table C, and E substituted with
(R4 is
Figure imgf000316_0004
Compund 161:
Compounds of formula 3A wherein R2, R3, M and R20ax corresponds to a row in Table C, and E substituted with (R4)n is:
Figure imgf000317_0001
Compund 162:
Compounds of formula 3A wherein R2, R3, M and R20ax corresponds to a row in Table C, and E substituted with
(R4 XS:
Figure imgf000317_0002
Compund 163:
Compounds of formula 3A wherein R2, R3, M and R20ax corresponds to a row in Table C, and E substituted with
( R' i s :
Figure imgf000317_0003
Compund 164 :
Compounds of formula 3A wherein R2, R3, M and R20ax corresponds to a row in Table C, and E substituted with
(R4 is :
Figure imgf000317_0004
Compund 165:
Compounds of formula 3A wherein R2, R3, M and R20ax corresponds to a row in Table C, and E substituted with (R4)n is:
Figure imgf000318_0001
Compund 166 :
Compounds of formula 3A wherein R2, R3, M and R20ax corresponds to a row in Table C, and E substituted with
( R4 i s
Figure imgf000318_0002
Compund 167 :
Compounds of formula 3A wherein R2, R3, M and R20ax corresponds to a row in Table C, and E substituted with (R4)n is:
Figure imgf000318_0003
Compund 168:
Compounds of formula 3A wherein R2, R3, M and R20ax corresponds to a row in Table C, and E substituted with
(R* xs
Figure imgf000318_0004
Compund 169:
Compounds of formula 3A wherein R2, R3, M and R20ax corresponds to a row in Table C, and E substituted with (R4)n is:
Figure imgf000319_0001
Compund 170:
Compounds of formula 3A wherein R2, R3, M and R2Oax corresponds to a row in Table C, and E substituted with
(R" is
Figure imgf000319_0002
Compund 171:
Compounds of formula 3A wherein R2, R3, M and R20ax corresponds to a row in Table C, and E substituted with
( R4 ) n i s :
Figure imgf000319_0003
Compund 172 :
Compounds of formula 3A wherein R2, R3, M and R2Oax corresponds to a row in Table C, and E substituted with
( R" i s
Figure imgf000319_0004
Compund 173 :
Compounds of formula 3A wherein R2, R3, M and R2Oax corresponds to a row in Table C, and E substituted with (R4)n is:
Figure imgf000320_0001
Compund 174:
Compounds of formula 3A wherein R2, R3, M and R20ax corresponds to a row in Table C, and E substituted with
( R4 i s :
Compund 175 :
Compounds of formula 3A wherein R2, R3, M and R20ax corresponds to a row in Table C, and E substituted with
(Rq is :
Figure imgf000320_0003
Compund 176:
Compounds of formula 3A wherein R2, R3, M and R20ax corresponds to a row in Table C, and E substituted with
(R* is :
Figure imgf000320_0004
Compund 177:
Compounds of formula 3A wherein R2, R3, M and j>20ax corresponds to a row in Table C, and E substituted with (R4)n is:
Figure imgf000321_0001
Compund 178:
Compounds of formula 3A wherein R2, R3, M and R20ax corresponds to a row in Table C, and E substituted with
(R4 is
Figure imgf000321_0002
Compund 179:
Compounds of formula 3A wherein R2, R3, M and R20ax corresponds to a row in Table C, and E substituted with
(R4)n is:
Figure imgf000321_0003
Compund 180:
Compounds of formula 3A wherein R2, R3, M and R20ax corresponds to a row in Table C, and E substituted with (R4)n is:
Figure imgf000321_0004
Compund 181:
Compounds of formula 3A wherein R2, R3, M and R20ax corresponds to a row in Table C, and E substituted with (R4)n is:
Figure imgf000322_0001
Compund 182 :
Compounds of formula 3A wherein R2, R3, M and R20ax corresponds to a row in Table C, and E substituted with
( R4 is :
Figure imgf000322_0002
Compund 183 :
Compounds of formula 3A wherein R2, R3, M and R20ax corresponds to a row in Table C, and E substituted with
(R4)n is:
Figure imgf000322_0003
Compund 184:
Compounds of formula 3A wherein R2, R3, M and R20ax corresponds to a row in Table C, and E substituted with (R4)n is:
Figure imgf000322_0004
Compund 185 :
Compounds of formula 3A wherein R2, R3, M and R20ax corresponds to a row in Table C, and E substituted with (R4)n is:
Figure imgf000323_0001
Compund 186:
Compounds of formula 3A wherein R2, R3, M and R2Oax corresponds to a row in Table C, and E substituted with (R4)n is:
Figure imgf000323_0002
Compund 187:
Compounds of formula 3A wherein R2, R3, M and R20ax corresponds to a row in Table C, and E substituted with ( R4 ) n is :
Figure imgf000323_0003
Compund 188 :
Compounds of formula 3A wherein R2, R3, M and R20ax corresponds to a row in Table C, and E substituted with
(R4 is
Figure imgf000323_0004
Compund 189:
Compounds of formula 3A wherein R2, R3, M and R20ax corresponds to a row in Table C, and E substituted with (R4)n is:
Figure imgf000324_0001
Compund 190:
Compounds of formula 3A wherein R2, R3, M and R20ax corresponds to a row in Table C, and E substituted with
(R4 xs :
Figure imgf000324_0002
Compund 191:
Compounds of formula 3A wherein R2, R3, M and R20ax corresponds to a row in Table C, and E substituted with
(R* is :
Figure imgf000324_0003
Compund 192:
Compounds of formula 3A wherein R2, R3, M and p>20ax corresponds to a row in Table C, and E substituted with (R4)n is:
Figure imgf000324_0004
Table C:
Figure imgf000324_0005
Figure imgf000325_0001
Figure imgf000326_0001
Figure imgf000327_0004
Figure imgf000327_0001
Compund 193:
Compounds of formula 4A wherein R^, RJ, M and R^ corresponds to a row in Table D, and E substituted with
(R4)n is:
Figure imgf000327_0002
Compund 194:
Compounds of formula 4A wherein R2, R3, M and R20ay corresponds to a row in Table D, and E substituted with
(R4)n is:
Figure imgf000327_0003
Compund 195: Compounds of formula 4A wherein R2, R3, M and R20ay corresponds to a row in Table D, and E substituted with
(Rq is
Figure imgf000328_0001
Compund 196:
Compounds of formula 4A wherein Rz, RJ, M and R^ corresponds to a row in Table D, and E substituted with
:R' IS
Figure imgf000328_0002
Compund 197:
Compounds of formula 4A wherein R2, R3, M and R20ay corresponds to a row in Table D, and E substituted with
(R4)n is:
Figure imgf000328_0003
Compund 198:
Compounds of formula 4A wherein Rz, RJ, M and Rz corresponds to a row in Table D, and E substituted with
( R4 ) n i s :
Figure imgf000328_0004
Compund 199 :
Compounds of formula 4A wherein R2, R3, M and R20ay corresponds to a row in Table D, and E substituted with
(R" is :
Figure imgf000329_0001
Compund 200:
Compounds of formula 4A wherein R"% RJ, M and R^ corresponds to a row in Table D, and E substituted with
(Rq is
Figure imgf000329_0002
Compund 201: Compounds of formula 4A wherein Rz, RJ, M and R^ corresponds to a row in Table D, and E substituted with
(R' is :
Figure imgf000329_0003
Compund 202: Compounds of formula 4A wherein RΔ, RJ, M and R^ corresponds to a row in Table D, and E substituted with
(R' is
Figure imgf000329_0004
Compund 203: Compounds of formula 4A wherein R2, R3, M and R20aγ corresponds to a row in Table D, and E substituted with (R4)n is:
Figure imgf000330_0001
Compund 204 :
Compounds of formula 4A wherein Rz, RJ, M and R^ corresponds to a row in Table D, and E substituted with (R4)n is:
Me
N
Compund 205 C.AΛ
Compounds of formula 4A wherein R , R , M and R y corresponds to a row in Table D, and E substituted with
(R* is
Figure imgf000330_0002
Compund 206:
Compounds of formula 4A wherein R^, RJ, M and Rz corresponds to a row in Table D, and E substituted with
(R4)n is:
Figure imgf000330_0003
Compund 207:
Compounds of formula 4A wherein R2, R3, M and R20ay corresponds to a row in Table D, and E substituted with (R4)π is:
Figure imgf000331_0001
Compund 208:
Compounds of formula 4A wherein R2, R3, M and R203^ corresponds to a row in Table D, and E substituted with
(R" is :
Figure imgf000331_0002
Compund 209:
Compounds of formula AA wherein R2, R3, M and R20ay corresponds to a row in Table D, and E substituted with
(R4 is :
Figure imgf000331_0003
Compund 210:
Compounds of formula 4A wherein R^, RJ, M and R^ corresponds to a row in Table D, and E substituted with (R4)n is:
Figure imgf000331_0004
Compund 211 :
Compounds of formula ' 4A wherein R2, R3, M and R20ay corresponds to a row in Table D, and E substituted with (R4)n is:
Figure imgf000332_0001
Compund 212:
Compounds of formula 4A wherein R^, RJ, M and R^ corresponds to a row in Table D, and E substituted with
(R4 is :
Figure imgf000332_0002
Compund 213:
Compounds of formula 4A wherein Rz, RJ, M and R^ corresponds to a row in Table D, and E substituted with (R4)n is:
Figure imgf000332_0003
Compund 214:
Compounds of formula 4A wherein R"% RJ, M and R^ corresponds to a row in Table D, and E substituted with
(R4 is :
Figure imgf000332_0004
Compund 215:
Compounds of formula 4A wherein Rz, RJ, M and R^ corresponds to a row in Table D, and E substituted with (R4)n is:
Figure imgf000333_0001
Compund 216:
Compounds of formula 4A wherein R2, R3, M and R20ay corresponds to a row in Table D, and E substituted with
(R' is
Figure imgf000333_0002
Compund 217:
Compounds of formula 4A wherein R2, R3, M and R20ay corresponds to a row in Table D, and E substituted with
(R4)n is:
Figure imgf000333_0003
Compund 218:
Compounds of formula 4A wherein R^, RJ, M and R^ corresponds to a row in Table D, and E substituted with
(R4)n IS
Figure imgf000333_0004
Compund 219:
Compounds of formula 4A wherein R2, R3, M and R20av corresponds to a row in Table D, and E substituted with (R4)n is:
Figure imgf000334_0001
Compund 220 :
Compounds of formula 4A wherein R^, RJ, M and R* corresponds to a row in Table D, and E substituted with
(R4 is
Figure imgf000334_0002
Compund 221:
Compounds of formula 4A wherein R2, R3, M and R2Oay corresponds to a row in Table D, and E substituted with
(R4)n is :
Figure imgf000334_0003
Compund 222:
Compounds of formula 4A wherein R2, R3, M and R20ay corresponds to a row in Table D, and E substituted with (R4)n is:
Figure imgf000334_0004
Compund 223:
Compounds of formula 4A wherein Rz, RJ, M and R^ corresponds to a row in Table D, and E substituted with (R' IS :
Figure imgf000335_0001
Compund 224:
Compounds of formula 4A wherein R2, R3, M and R20ay corresponds to a row in Table D, and E substituted with (R4)n is:
Figure imgf000335_0002
Compund 225 :
Compounds of formula 4A wherein Rz, RJ, M and R^ corresponds to a row in Table D, and E substituted with
( R4 i s
Figure imgf000335_0003
Compund 226 :
Compounds of formula 4A wherein Rz, RJ, M and R^ corresponds to a row in Table D, and E substituted with (R4)π is:
Figure imgf000335_0004
Compund 227 :
Compounds of formula 4A wherein Rz, RJ, M and Rz corresponds to a row in Table D, and E substituted with
(R4)n IS
Figure imgf000336_0001
Compund 228:
Compounds of formula 4A wherein Rz, RJ, M and R^ corresponds to a row in Table D, and E substituted with
(R4)n is:
Figure imgf000336_0002
Compund 229: Compounds of formula 4A wherein R2, R3, M and R20ay corresponds to a row in Table D, and E substituted with
(R4 is
Figure imgf000336_0003
Compund 230: Compounds of formula 4A wherein R2, R3, M and R20ay corresponds to a row in Table D, and E substituted with
(R4 is
Figure imgf000336_0004
Compund 231: Compounds of formula 4A wherein R2, R3, M and R20ay corresponds to a row in Table D, and E substituted with (R4)n is:
Figure imgf000337_0001
Compund 232:
Compounds of formula 4A wherein R2, R3, M and R20ay corresponds to a row in Table D, and E substituted with
(R' xs
Figure imgf000337_0002
Compund 233:
Compounds of formula 4A wherein Rz, RJ, M and R^ corresponds to a row in Table D, and E substituted with
Figure imgf000337_0003
Compund 234 :
Compounds of formula 4A wherein R^, R"3, M and R^ corresponds to a row in Table D, and E substituted with (R4)n is:
Figure imgf000337_0004
Compund 235: Compounds of formula 4A wherein R2, R3, M and R20ay corresponds to a row in Table D, and E substituted with
(R" is :
Figure imgf000338_0001
Compund 236:
Compounds of formula 4A wherein Rz, RJ, M and Rz corresponds to a row in Table D, and E substituted with
(R" is :
Figure imgf000338_0002
Compund 237:
Compounds of formula 4A wherein Rz, RJ, M and R^ corresponds to a row in Table D, and E substituted with
(Rq is :
Figure imgf000338_0003
Compund 238:
Compounds of formula 4A wherein R^, RJ, M and R^ corresponds to a row in Table D, and E substituted with (R4)n is:
Figure imgf000338_0004
Compund 239: Compounds of formula 4A wherein R2, R3, M and R20ay corresponds to a row in Table D, and E substituted with (R4)n is:
Figure imgf000339_0001
Compund 240:
Compounds of formula 4A wherein Rz, RJ, M and R^ corresponds to a row in Table D, and E substituted with (R4)n is:
Figure imgf000339_0002
Compund 241:
Compounds of formula 4A wherein R2, R3, M and R20ay corresponds to a row in Table D, and E substituted with (R4)n is:
Figure imgf000339_0003
Compund 242:
Compounds of formula 4A wherein R2, R3, M and R20ay corresponds to a row in Table D, and E substituted with (R4)n is:
Figure imgf000340_0001
Compund 243:
Compounds of formula 4A wherein R2, R3, M and R2Oay corresponds to a row in Table D, and E substituted with (R4)n is:
Figure imgf000340_0002
Compund 244 :
Compounds of formula 4A wherein R2, R3, M and R20ay corresponds to a row in Table D, and E substituted with
(R4 is
Figure imgf000340_0003
Compund 245:
Compounds of formula 4A wherein Rz, RJ, M and R^ corresponds to a row in Table D, and E substituted with
(R4 is
Figure imgf000340_0004
Compund 246:
Compounds of formula 4A wherein Rz, RJ, M and R^ corresponds to a row in Table D, and E substituted with (R4)n is:
Figure imgf000341_0001
Compund 247:
Compounds of formula 4A wherein Rz, RJ, M and R^ corresponds to a row in Table D, and E substituted with (R4)n is:
Compund 248:
Compounds of formula 4A wherein R^, RJ, M and R^ corresponds to a row in Table D, and E substituted with
(R4)n is:
Figure imgf000341_0003
Compund 249:
Compounds of formula 4A wherein Rz, RJ, M and Rz corresponds to a row in Table D, and E substituted with
(R4 is
Figure imgf000341_0004
Compund 250:
Compounds of formula 4A wherein R2, R3, M and R20ay corresponds to a row in Table D, and E substituted with (R4)n is:
Figure imgf000342_0001
Compund 251:
Compounds of formula 4A wherein R^, RJ, M and R^ corresponds to a row in Table D, and E substituted with
(R4 is
Figure imgf000342_0002
Compund 252:
Compounds of formula 4A wherein R2, R3, M and R20ay corresponds to a row in Table D, and E substituted with
(R4 is :
Figure imgf000342_0003
Compund 253:
Compounds of formula 4A wherein Rz, RJ, M and R^ corresponds to a row in Table D, and E substituted with
(R4)n is :
Figure imgf000342_0004
Compund 254:
Compounds of formula 4A wherein R2, R3, M and R2Oay corresponds to a row in Table D, and E substituted with (R4)n is:
Figure imgf000343_0001
Compund 255:
Compounds of formula 4A wherein Rz, RJ, M and Rz corresponds to a row in Table D, and E substituted with
( R4 i s
Figure imgf000343_0002
Compund 256 :
Compounds of formula 4A wherein R2, R3, M and R20ay corresponds to a row in Table D, and E substituted with
(R4)n is:
Figure imgf000343_0003
Compund 257:
Compounds of formula 4A wherein Rz, RJ, M and R^ corresponds to a row in Table D, and E substituted with
(R" is
Figure imgf000343_0004
Compund 258:
Compounds of formula 4A wherein R2, R3, M and R20ay corresponds to a row in Table D, and E substituted with (R4)n is:
Figure imgf000344_0001
Compund 259:
Compounds of formula 4A wherein Rz, RJ, M and R^ corresponds to a row in Table D, and E substituted with
(R" IS :
Figure imgf000344_0002
Compund 260:
Compounds of formula 4A wherein R2, R3, M and R20a¥ corresponds to a row in Table D, and E substituted with
(R4)n is:
Figure imgf000344_0003
Compund 261:
Compounds of formula 4A wherein Rz, RJ, M and R^ corresponds to a row in Table D, and E substituted with
(R4 is
Figure imgf000344_0004
Compund 262:
Compounds of formula 4A wherein R2, R3, M and R20ay corresponds to a row in Table D, and E substituted with (R4)n is:
Figure imgf000345_0001
Compund 263 :
Compounds of formula 4A wherein R2, R3, M and R20ay corresponds to a row in Table D, and E substituted with
(R4)n is:
N'T*
Compund 264:
Compounds of formula 4A wherein R2, R3, M and R20ay corresponds to a row in Table D, and E substituted with (R4)n is:
Figure imgf000345_0002
Compund 265:
Compounds of formula 4A wherein R2, R3, M and R20ay corresponds to a row in Table D, and E substituted with
(R4)n is:
Figure imgf000345_0003
Compund 266:
Compounds of formula 4A wherein R2, R3, M and R20ay corresponds to a row in Table D, and E substituted with (R4)n is:
Figure imgf000346_0001
Compund 267:
Compounds of formula 4A wherein Rz, RJ, M and R^ corresponds to a row in Table D, and E substituted with
(R4 is
Figure imgf000346_0002
Compund 268:
Compounds of formula 4A wherein Rz, RJ, M and R^ corresponds to a row in Table D, and E substituted with
(R4)n is:
Figure imgf000346_0003
Compund 269:
Compounds of formula 4A wherein Rz, RJ, M and R^ corresponds to a row in Table D, and E substituted with
(R* is
Figure imgf000346_0004
Compund 270:
Compounds of formula 4A wherein R2, R3, M and R20ay corresponds to a row in Table D, and E substituted with (R4)n is:
Figure imgf000347_0001
Compund 271:
Compounds of formula 4A wherein R2, R3, M and R20ay corresponds to a row in Table D, and E substituted with
(R4 is
Figure imgf000347_0002
Compund 272:
Compounds of formula 4A wherein R2, R3, M and R20ay corresponds to a row in Table D, and E substituted with
(Rq is
Figure imgf000347_0003
Compund 273:
Compounds of formula 4A wherein R^, RJ, M and R^ corresponds to a row in Table D, and E substituted with
(R4 xs
Figure imgf000347_0004
Compund 274:
Compounds of formula 4A wherein R2, R3, M and R20ay corresponds to a row in Table D, and E substituted with (R4)n is: Cf
Compund 275: Compounds of formula 4A wherein R2, R3, M and R20aγ corresponds to a row in Table D, and E substituted with
(R4 is :
Figure imgf000348_0001
Compund 276: Compounds of formula 4A wherein R2, R3, M and R20ay corresponds to a row in Table D, and E substituted with
[R4)n is:
<
Compund 277: Compounds of formula 4A wherein R2, R3, M and R2Oay corresponds to a row in Table D, and E substituted with
(R4)π is:
Figure imgf000348_0002
Table D:
Figure imgf000348_0003
Figure imgf000349_0001
Figure imgf000350_0001
Figure imgf000351_0001
Figure imgf000352_0001
Compound 278:
Compounds of formula 5A wherein R2, R3, M, R19a and R20ay corresponds to a row in Table E, and E substituted with (R4)n is:
Figure imgf000352_0002
Compound 279:
Compounds of formula 5A wherein R% RJ, M, R13a and R^ corresponds to a row in Table E, and E substituted with (R4)n is:
Figure imgf000352_0003
Compound 280:
Compounds of formula 5A wherein R2, R3, M, R19a and R20aγ corresponds to a row in Table E, and E substituted with
(R4 is :
Figure imgf000352_0004
Compound 281:
Compounds of formula 5A wherein R2, R3, M, R19a and R20ay corresponds to a row in Table E, and E substituted with (R4)n is:
Figure imgf000353_0001
Compound 282:
Compounds of formula 5A wherein Rz, RJ, M, R13a and R^ corresponds to a row in Table E, and E substituted with (R4)n is:
Figure imgf000353_0002
Compound 283:
Compounds of formula 5A wherein R2, R3, M, R19a and R20ay corresponds to a row in Table E, and E substituted with (R4)n is:
Figure imgf000353_0003
Compound 284
Compounds of formula 5A wherein R^, RJ, M, Rlva and R^ corresponds to a row in Table E, and E substituted with (R4)n is:
Figure imgf000353_0004
Compound 285: Compounds of formula 5A wherein R2, R3, M, R19a and R20ay corresponds to a row in Table E, and E substituted with
(R4 is
Figure imgf000354_0001
Compound 286:
Compounds of formula 5A wherein Rz, RJ, M, R13a and R" corresponds to a row in Table E, and E substituted with (R4)n is:
Figure imgf000354_0002
Compound 287:
Compounds of formula 5A wherein R^, RJ, M, R13a and Rz corresponds to a row in Table E, and E substituted with (R4)n is:
Figure imgf000354_0003
Compound 288:
Compounds of formula 5A wherein R2, R3, M, R19a and R20ay corresponds to a row in Table E, and E substituted with
(R4)n is:
Figure imgf000354_0004
Compound 289: Compounds of formula 5A wherein R , R3, M, R19a and R20ay corresponds to a row in Table E, and E substituted with (R4)n is:
Figure imgf000355_0001
Compound 290:
Compounds of formula 5A wherein R2, R3, M, R19a and R20ay corresponds to a row in Table E, and E substituted with (R4)n is:
Figure imgf000355_0002
Compound 291:
Compounds of formula 5A wherein R2, R3, M, R19a and R20ay corresponds to a row in Table E, and E substituted with
(R4)n is :
Figure imgf000355_0003
Compound 292:
Compounds of formula 5A wherein R^, RJ, M, R13a and R^ corresponds to a row in Table E, and E substituted with (R4)n is:
Figure imgf000355_0004
Compound 293:
Compounds of formula 5A wherein R2, R3, M, R19a and R2Oay corresponds to a row in Table E, and E substituted with
(R4 is :
Figure imgf000356_0001
Compound 294:
Compounds of formula 5A wherein R2, R3, M, R19a and R20ay corresponds to a row in Table E, and E substituted with
(R4 is
Figure imgf000356_0002
Compound 295:
Compounds of formula 5A wherein Rz, RJ, M, R13a and R^ corresponds to a row in Table E, and E substituted with (R4)n is:
Figure imgf000356_0003
Compound 296:
Compounds of formula 5A wherein R2, R3, M, R19a and R20aγ corresponds to a row in Table E, and E substituted with
!R4)n is:
Figure imgf000356_0004
Compound 297: Compounds of formula 5A wherein R , R , M, R 1193aa and R -,20ay corresponds to a row in Table E, and E substituted with
(R< is
Figure imgf000357_0001
Compound 298:
Compounds of formula 5A wherein R2, R3, M, R19a and R20ay corresponds to a row in Table E, and E substituted with
[R" xs :
Figure imgf000357_0002
Compound 299:
Compounds of formula 5A wherein R2, R3, M, R19a and R20ay corresponds to a row in Table E, and E substituted with
(R4)n is:
Figure imgf000357_0003
Compound 300:
Compounds of formula 5A wherein R2, R3, M, R19a and R20ay corresponds to a row in Table E, and E substituted with (R4)n is:
Figure imgf000357_0004
Compound 301:
Compounds of formula 5A wherein R2, R3, M, R19a and R20ay corresponds to a row in Table E, and E substituted with ( R4 ) n i s :
Figure imgf000358_0001
Compound 302:
Compounds of formula 5A wherein Rz, RJ, M, R13a and R^ corresponds to a row in Table E, and E substituted with (R4)n is:
Figure imgf000358_0002
Compound 303:
Compounds of formula 5A wherein R^, RJ, M, Rli)a and R^ corresponds to a row in Table E, and E substituted with (R4)n is:
Figure imgf000358_0003
Compound 304 :
Compounds of formula 5A wherein Rz, RJ, M, R133 and R^ corresponds to a row in Table E, and E substituted with (R4)n is:
Figure imgf000358_0004
Compound 305:
Compounds of formula 5A wherein R2, R3, M, R19a and R20ay corresponds to a row in Table E, and E substituted with (R4 xs
Figure imgf000359_0001
Compound 306:
Compounds of formula 5A wherein Rz, R-3, M, R13a and R^ corresponds to a row in Table E, and E substituted with (R4)n is:
Figure imgf000359_0002
Compound 307:
Compounds of formula 5A wherein Rz, RJ, M, Riaa and R^ corresponds to a row in Table E, and E substituted with (R4)n is:
Figure imgf000359_0003
Compound 308:
Compounds of formula 5A wherein R2, R3, M, R19a and R20ay corresponds to a row in Table E, and E substituted with (R4)n is:
Figure imgf000359_0004
Compound 309:
Compounds of formula 5A wherein R2, R3, M, R19a and R20ay corresponds to a row in Table E, and E substituted with (R4)n is:
Figure imgf000360_0001
Compound 310:
Compounds of formula 5A wherein R% RJ, M, R1*3 and R^ corresponds to a row in Table E, and E substituted with (R4)n is:
Figure imgf000360_0002
Compound 311:
Compounds of formula 5A wherein Rz, RJ, M, RL*a and R^ corresponds to a row in Table E, and E substituted with (R4)n is:
Figure imgf000360_0003
Compound 312:
Compounds of formula 5A wherein R2, R3, M, R19a and R20ay corresponds to a row in Table E, and E substituted with
(R4)n is :
Figure imgf000360_0004
Compound 313:
Compounds of formula 5A wherein R2, R3, M, R19a and R 20ay corresponds to a row in Table E, and E substituted with (R4)n is:
Figure imgf000361_0001
Compound 314:
Compounds of formula 5A wherein R2, R3, M, R19a and R20ay corresponds to a row in Table E, and E substituted with (R4)n is:
Figure imgf000361_0002
Compound 315:
Compounds of formula 5A wherein R2, R3, M, R19a and R20ay corresponds to a row in Table E, and E substituted with (R4)n is:
Figure imgf000361_0003
Compound 316:
Compounds of formula 5A wherein R2, R3, M, R19a and R20ay corresponds to a row in Table E, and E substituted with
(R4 is :
Figure imgf000361_0004
Compound 317:
Compounds of formula 5A wherein R2, R3, M, R19a and R20ay corresponds to a row in Table E, and E substituted with (R4)π is:
Figure imgf000362_0001
Compound 318:
Compounds of formula 5A wherein R2, R3, M, R19a and R20ay corresponds to a row in Table E, and E substituted with (R4)n is:
Figure imgf000362_0002
Compound 319:
Compounds of formula 5A wherein Rz, R-5, M, Riaa and Rz corresponds to a row in Table E, and E substituted with (R4)n is:
Figure imgf000362_0003
Compound 320:
Compounds of formula 5A wherein R^, RJ, M, R13a and R^ corresponds to a row in Table E, and E substituted with
(R4 IS :
Figure imgf000362_0004
Compound 321:
Compounds of formula 5A wherein R2, R3, M, R19a and R20ay corresponds to a row in Table E, and E substituted with (R4)n is:
Figure imgf000363_0001
Compound 322:
Compounds of formula 5A wherein R2, R3, M, R19a and R20ay corresponds to a row in Table E, and E substituted with (R4)n is:
Figure imgf000363_0002
Compound 323:
Compounds of formula 5A wherein Rz, RJ, M, R13a and R^ corresponds to a row in Table E, and E substituted with
(R4 is
Figure imgf000363_0003
Compound 324:
Compounds of formula 5A wherein R2, R3, M, R19a and R 20ay corresponds to a row in Table E, and E substituted with
(R* is
Figure imgf000363_0004
Compound 325:
Compounds of formula 5A wherein R2, R3, M, R19a and R20ay corresponds to a row in Table E, and E substituted with (R4)n is:
Figure imgf000364_0001
Compound 326:
Compounds of formula 5A wherein R^, RJ, M, Riaa and R^ corresponds to a row in Table E, and E substituted with (R4)n is:
Figure imgf000364_0002
Compound 327:
Compounds of formula 5A wherein Rz, RJ, M, R13a and R^ corresponds to a row in Table E, and E substituted with (R4)n is:
Figure imgf000364_0003
Compound 328:
Compounds of formula 5A wherein R2, R3, M, R19a and R20ay corresponds to a row in Table E, and E substituted with
(R' is
Figure imgf000364_0004
Compound 329:
Compounds of formula 5A wherein R2, R3, M, R19a and R20ay corresponds to a row in Table E, and E substituted with (R4)n is:
Figure imgf000365_0001
Compound 330:
Compounds of formula 5A wherein R2, R3, M, R19a and R20aγ corresponds to a row in Table E, and E substituted with (R4)n is:
Figure imgf000365_0002
Compound 331:
Compounds of formula 5A wherein R2, R3, M, R19a and R20ay corresponds to a row in Table E, and E substituted with (R4)n is:
Figure imgf000365_0003
Compound 332:
Compounds of formula 5A wherein R , R , M, R 19a and R ?20ay corresponds to a row in Table E, and E substituted with
(R* is
Figure imgf000365_0004
Compound 333:
Compounds of formula 5A wherein R2, R3, M, R19a and R20ay corresponds to a row in Table E, and E substituted with (R4)n is:
Figure imgf000366_0001
Compound 334 :
Compounds of formula 5A wherein Rz, RJ, M, Riaa and R^ corresponds to a row in Table E, and E substituted with (R4)n is:
Figure imgf000366_0002
Compound 335:
Compounds of formula 5A wherein R2, R3, M, R19a and R2Oay corresponds to a row in Table E, and E substituted with
(R" is
Figure imgf000366_0003
Compound 336:
Compounds of formula 5A wherein Rz, RJ, M, R13a and R" corresponds to a row in Table E, and E substituted with
(R< is :
Figure imgf000366_0004
Compound 337 :
Compounds of formula 5A wherein R2, R3, M, R19a and R20aγ corresponds to a row in Table E, and E substituted with (R4)n is:
Figure imgf000367_0001
Compound 338 :
Compounds of formula 5A wherein R , R3, M, R19a and R20ay corresponds to a row in Table E, and E substituted with (R4)n is:
Figure imgf000367_0002
Compound 339:
Compounds of formula 5A wherein R2, R3, M, R19a and R20ay corresponds to a row in Table E, and E substituted with
(R4)n is:
Figure imgf000367_0003
Compound 340:
Compounds of formula 5A wherein Rz, RJ, M, Riaa and R^ corresponds to a row in Table E, and E substituted with
(R4)n IS
Figure imgf000367_0004
Compound 341:
Compounds of formula 5A wherein R2, R3, M, R19a and R203^ corresponds to a row in Table E, and E substituted with (R4)n is:
Figure imgf000368_0001
Table E:
Figure imgf000368_0002
Figure imgf000369_0001
Figure imgf000370_0001
Figure imgf000371_0001
Figure imgf000372_0001
Figure imgf000373_0001
Figure imgf000374_0001
Figure imgf000375_0001
Examples of the pests against which the present compound has controlling efficacy include harmful arthropods such as harmful insects and harmful mites, and nemathelminths such as nematodes, and specific examples are as shown below.
Hemiptera : -
Planthoppers (Delphacidae) such as small brown planthopper {Laodelphax striatellus) , brown rice planthopper (Nilaparvata lugens) , and white-backed rice planthopper {Sogatella furcifera) ; leafhoppers (Deltocephalidae) such as green rice leafhopper {Nephotettix cincticeps) , green rice leafhopper {Nephotettix virescens) , and tea green leafhopper {Empoasca onukii) ; aphids (Aphididae) such as cotton aphid {Aphis gossypii) , green peach aphid {Myzus persicae) , cabbage aphid {Brevicoryne brassicae) , spiraea aphid (Aphis spiraecola) , potato aphid (Macrosiphum euphorbiae) , foxglove aphid {Aulacorthum solani) , oat bird-cherry aphid (Rhopalosiphum padi) , tropical citrus aphid (Toxoptera citricidus) , and mealy plum aphid {Hyalopterus pruni) ; stink bugs (Pentatomidae) such as green stink bug (Nezara antennata) , bean bug {Riptortus clavetus) , rice bug (Leptocorisa chinensis) , white spotted spined bug {Eysarcoris parvus) , and stink bug {Halyomorpha mista) ; whiteflies (Aleyrodidae) such as greenhouse whitefly (Trialeurodes vaporariorum) , sweetpotato whitefly (Bemisia tabaci) , silver leaf whitefly (Bemisia argentifolii) , citrus whitefly (Dialeurodes citri) , and citrus spiny white fly {Aleurocanthus spiniferus) ; scales (Coccidae) such as Calfornia red scale (Aonidiella aurantii) , San Jose scale (Comstockaspis perniciosa) , citrus north scale (Unaspis citri), red wax scale (Ceroplastes rubens) , cottonycushion scale (Icerya purchasi) , Japanese mealybug (Planococcus kraunhiae) , Cosmstock mealybug (Pseudococcus longispinis) , and white peach scale (Pseudaulacaspis pentagona) ; lace bags (Tingidae) ; psyllids (Psyllidae) ; etc.
Lepidoptera : - Pyralid moths (Pyralidae) such as rice stem borer (Chilo suppressalis) , yellow rice borer (Tryporyza incertulas) , rice leafroller (Cnaphalocrocis medinalis) , cotton leafroller (Notarcha derogata) , Indian meal moth {Plodia interpunctella) , oriental corn borer {Ostrinia furnacalis) , cabbage webworm (Hellula undalis) , and bluegrass webworm (Pediasia teterrellus) ; owlet moths (Noctuidae) such as common cutworm (Spodoptera litura) , beet armyworm (Spodoptera exigua) , armyworm (Pseudaletia separata) , cabbage armyworm (Mamestra brassicae) , black cutworm (Agrotis ipsilon) , beet semi-looper (Plusia nigrisigna) , Thoricoplusia spp . , Heliothis spp., and Helicoverpa spp.; whites and sulfer butterflies (Pieridae) such as common white {Pieris rapae) ; tortricid moths (Tortricidae) such as Adoxophyes spp., oriental fruit moth {Grapholita molesta) , soybean pod borer (Leguminivora glycinivorella) , azuki bean podworm {Matsumuraeses azukivora) , summer fruit tortrix {Adoxophyes orana fasciata) , Adoxophyes sp . , oriental tea tortrix {Homona magnanima) , apple tortrix {Archips fuscocupreanus) , and Cydia pomonella; leafblotch miners (Gracillariidae) such as tea leafroller (Caloptilia theivora) , and apple leafminer (Phyllonorycter ringoneella) ; Carposinidae such as peach fruit moth {Carposina niponensis) ; lyonetiid moths (Lyonetiidae) such as Lyonetia spp.; tussock moths (Lymantriidae) such as Lymantria spp., and Euproctis spp.; yponomeutid moths (Yponomeutidae) such as diamondback {Plutella xylostella) ; gelechiid moths (Gelechiidae) such as pink bollworm {Pectinophora gossypiella) , and potato tubeworm (Phthorimaea operculella) ; tiger moths and allies (Arctiidae) such as fall webworm (Hyphantria cunea) ; tineid moths (Tineidae) such as casemaking clothes moth {Tinea translucens) , and webbing clothes moth {Tineola bisselliella) ; etc.
Thysanoptera : - Thrips (Thripidae) such as yellow citrus thrips (Frankliniella occidentalis) , Thrips parmi, yellow tea thrips {Scirtothrips dorsalis) , onion thrip {Thrips tabaci) , flower thrips (Frankliniella intonsa) , etc.
Diptera : -
Housefly {Musca domestica) , common mosquito (Culex popiens pallens) , horsefly {Tabanus trigonus) , onion maggot {Hylemya antiqua) , seedcorn maggot {Hylemya platura) , Anopheles sinensis, rice leafminer (Agromyza oryzae) , rice leafminer {Hydrellia griseola) , rice stem maggot (Chlorops oryzae) , melon fly (Dacus cucurbitae) , Ceratitis capitata, legume leafminer (Liriomyza trifolii) , tomato leafminer (Liriomyza sativae) , garden pea leafminer ( Chromatomyia horticola) , etc.
Coleoptera: -
Twenty-eight-spotted ladybird (Epilachna vigintioctopunctata) , cucurbit leaf beetle (Aulacophora femoralis) , striped flea beetle (Phyllotreta striolata) , rice leaf beetle {Oulema oryzae) , rice curculio (Echinocnemus squameus) , rice water weevil {Lissorhoptrus oryzophilus) , Anthonomus grandis, azuki bean weevil {Callosobruchus chinensis) , Sphenophorus venatus, Japanese beetle [Popillia japonica) , cupreous chafer (Anomala cuprea) , corn root worm {Diabrotica spp . ) , Colorado beetle (Leptinotarsa decemlineata) , click beetle (Agriotes spp.) , cigarette beetle (Lasioderma serricorne) , varied carper beetle (Anthrenus verbasci) , red flour beetle (Tribolium castaneum) , powder post beetle {Lyctus brunneus) , white- spotted longicorn beetle (Anoplophora malasiaca) , pine shoot beetle {Tomicus piniperda) , etc.
Orthoptera : - Asiatic locust {Locusta migratoria) , African mole cricket {Gryllotalpa africana) , rice grasshopper {Oxya yezoensis) , rice grasshopper (Oxya japonica), etc.
Hymenoptera : - Cabbage sawfly (Athalia rosae) , Acromyrmex spp., fire ant (Solenopsis spp.), etc.
Nematodes : -
Rice white-tip nematode {Aphelenchoides besseyi) , strawberry bud nematode {Nothotylenchus acris) , southern root-knot nematode (Meloidogyne incognita) , northern root- knot nematode (Meloidogyne hapla) , Javanese root-knot nematode (Meloidogyne javanica) , soybean cyst nematode (Heterodera glycines) , potato cyst nematode (Globodera rostochiensis) , coffee root-lesion nematode (Pratylenchus coffeae) , California root-lesion nematode {Pratylenchus neglectus) , etc.
Dictyoptera : - German cockroach (Blattella germanica) , smokybrown cockroach {Periplaneta fuliginosa) , American cockroach {Periplaneta americana) , Periplaneta brunnea, oriental cockroach [Blatta orientalis) , etc.
Acarina:-
Spider mites (Tetranychidae) such as two-spotted spider mite {Tetranychus urticae) , Kanzawa spider mite (Tetranychus kanzawai) , citrus red mite (Panonychus citri) , European red mite (Panonychus ulmi) , and Oligonychus spp.; eriophyid mites (Eriophyidae) such as pink citrus rust mite (Aculops pelekassi) , pink citrus rust mite {Phyllocoptruta citri) , tomato rust mite {Aculops lycopersici) , purple tea mite (Calacarus carinatus) , pink tea rust mite {Acaphylla theavagran) , and Eriophyes chibaensis; tarosonemid mites ■ (Tarsonemidae) such as broad mite {Polyphagotarsonemus latus) ; false spider mites (Tenuipalpidae) such as Brevipalpus phoenicis; Tuckerellidae; ticks (Ixodidae) such as Haemaphysalis longicornis, Haemaphysalis flava, Dermacentor taiwanicus, Ixodes ovatus, Ixodes persulcatus, Boophilus microplus, and Rhipicephalus sanguineus; acarid mites (Acaridae) such as mold mite (Tyrophagus putrescentiae) , and Tyrophagus similis; house dust mites
(Pyroglyphidae) such as Dermatophagoides farinae, and Dermatophagoides ptrenyssnus; cheyletide mites (Cheyletidae) such as Cheyletus eruditus, Cheyletus malaccensis, and Cheyletus moorei; parasitoid mites
(Dermanyssidae) ; etc.
The pesticide of the present invention may be the present compound itself but, usually, the present compound is mixed with an inert carrier such as a solid carrier, a liquid carrier, a gaseous carrier and the like and, if necessary, a surfactant, and other preparation additives are added to formulate into a composition or a preparation such as an emulsion, oil, powder, granules, a wettable preparation, a flowable preparation, microcapsules, an aerosol, a fumigant, poison bait, a resin preparation or the like. These compositions or preparations usually contain 0.01 to 95% by weight of the present compound.
Examples of the solid carrier to be used include fine powders and granules such as clays (kaolin clay, diatomaceous earth, bentonite, fubasami clay, acid clay, etc.), synthetic hydrous silicon oxide, talc, ceramic, other inorganic minerals (sericite, quartz, sulfur, active carbon, calcium carbonate, hydrated silica, etc.), chemical fertilizers (ammonium sulfate, ammonium phosphate, ammonium nitrate, urea, ammonium chloride, etc.) and the like.
Examples of the liquid carrier include water, alcohols (methanol, ethanol, isopropyl alcohol, butanol, hexanol, benzyl alcohol, ethylene glycol, propylene glycol, phenoxyethanol, etc.), ketones (acetone, methyl ethyl ketone, cyclohexanone, etc.), aromatic hydrocarbons (toluene, xylene, ethylbenzene, dodecylbenzene, phenylxylylethane, methylnaphthalene, etc.), aliphatic hydrocarbons (hexane, cyclohexane, kerosene, gas oil, etc.), esters (ethyl acetate, butyl acetate, isopropyl myristate, ethyl oleate, diisopropyl adipate, diisobutyl adipate, propylene glycol monomethyl ether acetate, etc.), nitriles (acetonitrile, isobutyronitrile, etc.), ethers (diisopropyl ether, 1,4-dioxane, ethylene glycol dimethyl ether, diethylene glycol dimethyl ether, diethylene glycol monomethyl ether, propylene glycol monomethyl ether, dipropylene glycol monomethyl ether, 3-methoxyl-3-methyl-l- butanol, etc.), acid amides (N, N-dimethylformamide, N, N- dimethylacetamide, etc.), halogenated hydrocarbons (dichloromethane, trichloroethane, carbon tetrachloride, etc.), sulfoxides (dimethyl sulfoxide, etc.), carbonic propylene and vegetable oils (soybean oil, cottonseed oil, etc. ) . Examples of the gaseous carrier include fluorocarbon, butane gas, LPG (liquefied petroleum gas), dimethyl ether, and carbonic acid gas.
Examples of the surfactant include nonionic surfactants such as polyoxyethylene alkyl ether, polyoxyethylene alkyl aryl ether, polyethylene glycol fatty acid ester, and the like, and anionic surfactants such as alkyl sulfonate salts, alkylbenzene sulfonate salts and alkyl sulfate salts. Examples of other preparation additives include binders, dispersing agents, coloring agents and stabilizers, specifically, casein, gelatin, sugars (starch, gum arabic, cellulose derivatives, alginic acid, etc.), lignin derivatives, bentonite, synthetic water-soluble polymers (polyvinyl alcohol, polyvinylpyrrolidone, polyacrylic acids, etc.), PAP (acidic isopropyl phosphate), BHT (2, 6-di-tert- butyl-4- methylphenol) , and BHA(a mixture of 2-tert-butyl- 4- methoxyphenol and 3-tert-butyl-4-methoxyphenol) .
The method of controlling a pest of the present invention is usually performed by applying the pesticide of the present invention directly to a pest or to a place where a pest inhabits (plant, soil, in house, animal, etc.) . When the pesticide of the present invention is used for controlling a pest in the agricultural field, an amount to be applied is usually 1 to 10,000 g per 10,000 m2 in terms of the amount of the present compound. When the pesticide of the present invention is formulated into an emulsion, a wettable preparation, a flowable preparation or the like, usually, the agent is applied by diluting with water so that the active ingredient concentration becomes 0.01 to 10,000 ppm, and granules, powder or the like are usually applied as they are.
These preparations, or preparations diluted with water may be directly applied to a pest or to a plant such as a crop to be protected against a pest, or may be applied to soil of a cultivated land in order to control a pest inhabiting in the soil.
Alternatively, treatment may be performed for example, by winding a sheet-like or string-like-processed resin preparation on a crop, surrounding a crop with the resin preparation, or laying the resin preparation on soil about roots of a crop.
When the pesticide of the present invention is used for controlling a pest which inhabits in a house (e.g. fly, mosquito, cockroach, etc.), the amount to be applied is usually 0.01 to 1000 mg per 1 m2 of treating area in terms of the amount of the present compound in case of surface treatment, and is usually 0.01 to 500 mg per 1 m3 of treating space in terms of the amount of the present of compound in case of spatial treatment. When the pesticide of the present invention is formulated into an emulsion, a wettable preparation, a flowable preparation or the like, usually, the agent is applied by diluting with water so that the active ingredient concentration becomes 0.1 to
1000 ppm, and oil, an aerosol, a fumigant, poison bait or the like is applied as it is.
The pesticide of the present invention may contain other harmful arthropod controlling agents, acaricides, nematicides, fungicides, herbicides, plant growth regulators, synergists, fertilizers, soil conditioners, animal feeds, and the like.
As the active ingredients of the aforementioned other harmful arthropod controlling agents, acaricides and/or nematicides, for example, the following compounds can be mentioned. (1) Organic phosphorus 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, itiethiocarb, NAC, oxamyl, pirimicarb, propoxur : PHC, XMC, thiodicarb, xylylcarb, 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, 2,3,5,6-tetrafluoro-4- methylbenzyl (EZ) - (IRS, 3RS; IRS, 3SR) -2, 2-dimethyl-3-prop-l- enylcyclopropanecarboxylate, 2,3,5, 6-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) Neonicotinoid compounds Imidacloprid, nitenpyram, acetamiprid, thiamethoxam, thiacloprid, dinotefuran, clothianidin, and the like.
(6) Benzoylurea compounds
Chlorfluazuron, bistrifluron, diafenthiuron, diflubenzuron, fluazuron, flucycloxuron, flufenoxuron, hexaflumuron, lufenuron, novaluron, noviflumuron, teflubenzuron, triflumuron, and the like.
(7) Phenylpyrazole compounds
Acetoprole, ethiprole, fipronil, vaniliprole, pyriprole, pyrafluprole, and the like. (8) Bt toxin insecticides
Viable endospores derived from Bacillus thuringiensis and crystalline toxins produced by it, as well as a mixture of 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, 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, formetanate, metam-ammonium, metam-sodium, Methyl bromide, nidinotefuran, Potassium oleate, protrifenbute, spiromesifen, sulfur, metaflumizone, spirotetramat , and the like. Acaricides
Acequinocyl, amitraz, benzoximate, bromopropylate, chinomethionat, chlorobenzilate, CPCBS (chlorfenson) , clofentezine, Kelthane (dicofol) , etoxazole, fenbutatin oxide, fenothiocarb, fenpyroximate, fluacrypyrim, fluproxyfen, hexythiazox, propargite :BPPS, polynactins, pyridaben, Pyrimidifen, tebufenpyrad, tetradifon, spirodiclofen, amidoflumet, Bifenazate, Cyflumetofen, and the like.
Nematicides (nematicidal active ingredients) DCIP, fosthiazate, levamisol, methyisothiocyanate, morantel tartarate, and the like.
The present invention will be explained in more detail below by way of Preparation Examples, Formulation Examples, Test Examples, but the present invention is not limited to these Examples.
First, Preparation Examples of the present compound will be explained. Preparation examples:
Example 1: Preparation of N'- (3- { [5-bromo-2- (3-chloro- pyridin-2-yl) -2ff-pyrazole-
3-carbonyl] -amino}-2, 6-dichloro-pyridine-4-carbonyl) - hydrazinecarboxylic acid methyl ester (1)
Step 1: Preparation of pyrazole-1-sulfonic acid dimethylamide
Pyrazole (15 g) was dissolved in toluene (200 mL) and dimethylsulfamoyl chloride (23.7 mL) was slowly added. After addition of triethylamine (40 itiL) , the solution was stirred for 18 h at room temperature. The precipitate was filtered off, the filtrate concentrated in vacuum and the residue purified by column chromatography (silica gel 60, hexane/ethyl acetate = 5:1, then 2:1, Rf = 0.30 in hexane/ethyl acetate = 2:1, KMnO^-solution) to afford 17.6 g of the title compound of the formula
SO2NMe2 as a colorless oil. 1H-NMR (CDCl3, TMS) δ (ppm) : 2.95 (6H, s), 6.40 (IH, dd, J = 3 Hz, '2 Hz), 7.75 (I H, d, J = 2 Hz), 7.95 (1 H, dd, J = 3 Hz, 1 Hz) .
Step 2: Preparation of 3-bromo-pyrazole-l-sulfonic acid dimethylamide
Pyrazole-1-sulfone acid dimethylamide (17.6 g) was dissolved in dry THF (200 mL) and cooled to -78°C. A solution of n-butyllithium (80 mL, 1.3 M) was added slowly over a period of 15 min and stirred for further 15 min at - 78°C. A solution of 1, 2-dibromo-l, 1, 2 , 2-tetrachloroethane
(35.8 g) in dry THF (60 mL) was added within 10 min to this solution and stirred for further 15 min at -78°C, then the cool bath was removed and the mixture was quenched with water after stirring for 1 h. The reaction mixture was extracted 3x with ethyl acetate, the combined org. layers were washed with brine, dried over MgSO4 and concentrated in vacuum.
The residue was purified by column chromatography (silica gel 60, hexane/ethyl acetate = 5:1, Rf = 0.25) to afford 21.3 g of the title compound of the formula
Figure imgf000392_0001
e2 as a colorless oil.
1H-NMR (CDCl3, TMS) δ (ppm) : 3.08 (6H, s) , 6.43 (IH, m) , 7.61 IH, m) .
Step 3: Preparation of 3-bromo-lff-pyrazole
To 3-bromo-pyrazole-l-sulfonic acid dimethylamide (21.3 g) was slowly added trifluoroacetic acid (30 mL) and stirred at room temperature for 2 h. Hexane was added and the formed precipitate was filtered off and washed with hexane. The filtrate was diluted with MTB-ether, washed with sat. NaHC03-solution, water and brine, dried over MgSO4 and concentrated in vacuum to afford 10.7 g of a colorless oil containing 80% of the title compound of the formula
Br
H The residue was used for the next step without further purification .
1H-NMR (CDCl3, TMS) 8 (ppm) : 6.37 (IH, d, J = 3 Hz), 7.55 (IH, d, J = 3 Hz), 12.6 (IH, br s).
Step 4: Preparation of 2- (3-bromo-pyrazol-l-yl) -3-chloro- pyridine
The crude product of 3-bromo-lH-pyrazole (10.7 g) was dissolved in DMF (80 mL) , 2, 3-dichloropyridine (11.8 g) and caesium carbonate (57.3 g) were added and the mixture was stirred for 8 h at 100 °C . After addition of water, the mixture was extracted 2x with MTB-ether, the combined org. layers were washed 2x with water, brine, dried over MgSO4 and concentrated in vacuum. The residue was purified by column chromatography (silica gel 60, hexane/ethyl acetate = 5:1 , Rf = 0.20) to afford
12.9 g of the title compound of the formula
Figure imgf000393_0001
as a white solid. 1H-NMR (CDCl3, TMS) δ (ppm) : 6.51 (IH, d, J = 3Hz), 7.31 (IH, dd, J= 8 Hz, 5 Hz) , 7.91 (IH, dd, J= 8 Hz, 2 Hz) , 8.04 (IH, d, J= 3 Hz) , 8.45 (IH, dd, J= 5 Hz, 2 Hz) . Step 5: Preparation of 5-bromo-2- (3-chloro-pyridin-2-yl) -
2ff-pyrazole-3-carboxylic acid
2- (3-Bromo-pyrazol-l-yl) -3-chloro-pyridine (9.2 g) was dissolved in dry THF (80 πiL) and cooled to -78°C. A solution of LDA (21.3 mL, 2.0 M) was added over a period of 10 min and stirred for further 15 min at -78°C. The solution was poured on crushed dry ice in THF (50 mL) and stirred for additional 1 h. Water and Et2O were added and 2 N NaOH-solution was added to adjust the pH to 10-12. The layers were separated and the aqueous layer was washed 2x with Et2O and acidified with 2N HCl (pH ~ 3) . The resulting suspension was 3x extracted with MTB-ether, the combined org. layers were washed with brine, dried over MgSO4 and concentrated to afford 7.96 g of the title compound of the formula
Figure imgf000394_0001
as an orange solid.
1H-NMR (DMSO-d6) δ (ppm) : 7.23 (IH, s) , 7.68 (IH, dd, J= 8 Hz, 5 Hz), 8.24 (IH, dd, J =8 Hz, 2 Hz), 8.55 (IH, dd, J = 5 Hz, 2 Hz) . Step 6: Preparation of 3-aminoisonicotinic acid methyl ester
3-Aminoisonicotinic acid (400 mg) was suspended in methanol
(6 mL) and toluene (18 mL) was added. A solution of (trimethylsilyl) diazomethane (2.0 M in diethyl ether, 1.88 mL) was added slowly to the suspension. Within 5 to 10 minutes after addition, the suspension turned into a solution. After 2 hours stirring at room temperature, the reaction mixture was quenched with water and extracted 3x with ethyl acetate. The combined organic layer was washed with 2N hydrochloric acid, saturated bicarbonate solution and brine, dried over MgSO4 and concentrated in vacuum. The residue was purified by column chromatography (silica gel 60, hexane/ethyl acetate = 1:2, Rf = 0.40) to afford 340 mg of the title compound of the formula
Figure imgf000395_0001
as a white solid.
1H-NMR (CDCl3, TMS) δ (ppm) : 3.91 (3H, s), 5.65 (2H, br s), 7.59 (IH, d, J = 5 Hz), 7.93 (IH, d, J = 5 Hz), 8.19 (IH, s) .
Step 7: Preparation of 3-amino-2 , 6-dichloroisonicotinic acid methyl ester
3-Aminoisonicotinic acid methyl ester (340 mg) was dissolved in DMF (3 inL) , N-chlorosuccinimide (600 mg) was added and the resulting solution was stirred for 15 hours at room temperature. The product was precipitated by- addition of water to the reaction mixture, filtered off and washed with water. The crude product was purified by column chromatography (silica gel 60, hexane/ethyl acetate = 3:1, Rf = 0.50) to afford 460 mg of the title compound of the formula
Figure imgf000396_0001
as a white solid .
1H-NMR (CDCl3, TMS ) δ (ppm) : 3 . 94 ( 3H, s ) , 6 . 17 ( 2H, br s ) , 7 . 66 ( IH , s ) .
Step 8: Preparation of 3-amino-2, 6-dichloroisonicotinic acid
3-Amino-2, 6-dichloroisonicotinic acid methyl ester (460 mg) was dissolved in ethanol (8 mL) , water (2 mL) and potassium hydroxide (234 mg) was added. The solution was stirred for 20 minutes at room temperature and for 1.5 hours under reflux. After cooling to room temperature, 2N hydrochloric acid was added to adjust the pH-value to ~3 and the so- formed yellow precipitate was extracted 3x with ethyl acetate. The combined organic layer was washed with brine, dried over MgSO4 and concentrated in vacuum to afford 420 mg of the title compound of the formula
Figure imgf000397_0001
as a yellow solid. The compound was used in the following reaction step without further purification
1H-NMR (CDCl3, TMS) δ (ppm) : 6.21 (2 H, br s), 7.69 (1 H, s) .
Step 9: Preparation of 2- [5-bromo-2- (3-chloro-pyridin-2- yl) -2H-pyrazol-3-yl] -
6, 8-dichloro-pyrido [3,4-d] [1,3] oxazin-4-one
A mixture of 5-bromo-2- (3-chloro-pyridin-2-yl) -2H-pyrazole -3-carboxylic acid (example 1, step 5) (745 mg) and thionyl chloride (540μl) was stirred under reflux for 2 hours. Excess thionyl chloride was co-evaporated with dry toluene on a evaporator, the residue was re-dissolved in dry acetonitrile (10 itiL) and 3-amino-2, 6-dichloroisonicotinic acid (example 1, step 8) (745 mg) was added. The solution was stirred for 5 minutes at room temperature and triethylamine (490 μL) was added and stirred for 1 hour, before a second portion of triethylamine (490 μL) was added. After the mixture was stirred for further 30 minutes at room temperature, methanesulfonyl chloride (210 μL) was added. After stirring for 20 hours at room temperature, the formed precipitate was filtered off, washed carefully with water and MTB-ether and dried in vacuum to afford 731 mg of the title compound of the formula
Figure imgf000398_0001
as a yellow solid.
1H-NMR (CDCl3, TMS) 6 (ppm) : 7.32 (IH, s), 7.51 (IH, dd, J = 8 Hz, 5 Hz), 7.94 (IH, s), 7.99 (IH, dd, J= 8 Hz, 2 Hz), 8.55 (IH, dd, J= 5 Hz, 2 Hz).
Step 10: Preparation of N'- (3- { [5-bromo-2- (3-chloro-pyridin -2-yl) -2H-pyrazole-3-carbonyl] -amino}-2, 6-dichloro- pyridine-4-carbonyl ) -hydrazinecarboxylic acid methyl ester (1) 2- [5-Bromo-2- (3-chloro-pyridin-2-yl) -2H-pyrazol-3-yl] - 6, 8-dichloro-pyrido [3, 4-d] [1, 3] oxazin-4-one (200 mg) was dissolved in DMF (8 mL) under slight warming up. Carbazaic acid methyl ester (380 mg) was added and the solution was stirred for 25 hours at room temperature. The reaction mixture was quenched with water and extracted with MTB- ether. The organic layer was washed 3x with water, brine, dried over MgSO4 and concentrated in vacuum. The residue was purified by column chromatography (silica 60, hexane/ethyl acetate = 1:2, Rf = 0.20) to afford 190 mg of compound 1 of the pre'sent invention of the formula
Figure imgf000399_0001
as a white solid.
1H-NMR (DMSO-D6) δ (ppm) : 3.48-3.65 (3H, m) , 7.41 (IH, s), 7.60-7.63 (2H, m) , 8.18 (IH, d, J = 8 Hz), 8.51 (IH, d, J 5 Hz), 9.47 (IH, br s), 10.47 (IH, br s) , 10.76 (IH, br s)
Example 2: Preparation of N'- (2 , 6-dichloro-3- { [2- (3-chloro- pyridin-2-yl) -5-trifluoro methyl-2H-pyrazole-3-carbonyl] -amino} -pyridine-4-carbonyl) - hydrazinecarboxylic acid methyl ester (2)
Step 1: Preparation of 3-chloro-2- (3-trifluoromethyl- pyrazol -1-yl) -pyridine
3-Trifluoromethyl-lE-pyrazole (15.30 g) , 2, 3-dichloro- pyridine (16.64 g) and potassium carbonate (26.42 g) were suspended in dry DMF (100 mL) and stirred for 3 h at 130°C, overnight at rt and again for 11 h at 130°C.
After complete consumption of the starting material, the reaction was cooled to room temperature and quenched with water. The mixture was extracted 2x with ethyl acetate, the combined org. layers were washed 2x with water, brine, dried over MgSO4 and concentrated in vacuum.
The residue was purified by column chromatography (silica gel 60, hexane/ethyl acetate = 8:1, then 5:1, Rf = 0.35 in hexane/ethyl acetate = 3:1) to afford 22.88 g of the title compound of the formula
Figure imgf000400_0001
as a colorless oil.
1H-NMR (CDCl3, TMS) δ (ppm) : 6.75 (IH, d, J = 2 Hz), 7.37 (IH, dd, J= 8 Hz, 5 Hz), 7.95 (IH, dd, J= 8 Hz, 2 Hz), 8.14 (IH, d, J= 2 Hz), 8.49 (IH, dd, J= 5 Hz, 2 Hz).
Step 2: Preparation of 2- (3-chloro-pyridin-2-yl) -5- trifluoro methyl-2H-pyrazole- 3-carboxylic acid 3-Chloro-2- (3-trifluoromethyl-pyrazol-1-yl) -pyridine (15 g) was dissolved in dry THF (150 mL) and cooled to -78°C. A solution of LDA (39 mL, 2.0 M) were added over a period of 15 min and stirred for further 15 min at -78°C. The flask was connected to a gas inlet and CO2 was bubbled through the solution in a rate that the inner temperature was kept below -60 °C . The solution turned to pale yellow and the cool bath was removed after further 10 min stirring at - 78°C and the CO2-Stream stopped. After the solution warmed up to room temperature, 200 ml water and 200 ml hexane were added, and 2 N NaOH-solution was added to adjust the pH to 10-12. The layers were separated and the organic layer was again 2x extracted with 0.5 N NaOH-solution. The combined aqueous solutions were washed 2x with Et2θ and acidified with 2N HCl (pH ~ 3) . The resulting suspension was 3x extracted with MTB-ether, the combined org. layers were washed with brine, dried over MgSO4 and concentrated to afford 16.08 g of the title compound of the formula
Figure imgf000401_0001
as beige solid. The compound was used for the next step without further purification.
1H-NMR (DMSO-dg) δ (ppm) : 7.60 (IH, s), 7.74 (IH, dd, J= 8 Hz, 5 Hz), 8.30 (IH, dd, J = 8 Hz, 2 Hz), 8.60 (IH, dd, J = 5 Hz, 2 Hz) .
Step 3: Preparation of 2- (3-chloro-pyridin-2-yl) -5- trifluoro methyl-2H-pyrazole- 3-carbonyl chloride 2- (3-Chloro-pyridin-2-yl) -5-trifluoromethyl-2tf-pyrazole-3- carboxylic acid (16.08 g) was mixed with thionyl chloride (12 mL) and heated under reflux for 2 h. The excess thionyl chloride was evaporated from the crude solution on a rotary evaporator under co-evaporation with dry toluene. The acid chloride was isolated by distillation of the residue under reduced pressure (125 °C /3 mmHg) to afford 14.2 g of the title compound of the formula
Figure imgf000402_0001
as a crystalline solid. 1H-NMR (CDCl3, TMS) δ (ppm) : 7.52 (IH, s), 7.52 (IH, dd, J = 8 Hz, 5 Hz), 7.97 (IH, dd, J= 8 Hz, 2 Hz), 8.53 (IH, dd, J = 5 Hz, 2 Hz) .
Step 4 : Preparation of 6, 8-dichloro-2- [2- (3-chloro-pyridin -2-yl) -5-trifluoromethyl-2ff-pyrazol-3-yl] -pyrido [3, 4-d] [1, 3] oxazin-4-one
5-Trifluoromethyl-2- (3-chloro-pyridin-2-yl) -2H-pyrazole-3- carboxylic acid chloride (example 2, step 3) (242 mg) was added to a mixture of 3-amino-2 , 6-dichloroisonicotinic acid (example 1, step 8) (190 mg) in acetonitrile (3 mL) . The mixture was stirred for 5 minutes at room temperature and triethylamine (220 μL) was added and stirred for 20 minutes, before a second portion of triethylamine (220 μL) was added. After the mixture was stirred for further 20 minutes at room temperature, methanesulfonyl chloride (70 μL) was added. After stirring for 2 hours at room temperature, the formed precipitate was filtered off, washed carefully with water and MTB-ether and dried in vacuum to afford 350 mg of the title compound of the formula
Figure imgf000403_0001
as a yellow solid. 1H-NMR (CDCl3, TMS) 6 (ppm) : 7.54-7.57 (2H, m) , 7.88 (IH, s), 8.01-8.04 (IH, m) , 8.56-8.58 (IH, m) .
Step 5: Preparation of N'- (2, 6-dichloro-3- { [2- (3-chloro- pyridin-2-yl) -5-trifluoromethyl-2ff-pyrazole-3-carbonyl] - amino} -pyridine-4-carbonyl) -hydrazinecarboxylic acid methyl ester (2)
6, 8-Dichloro-2- [2- (3-chloro-pyridin-2-yl) -5- trifluoromethyl-2iϊ-pyrazol-3-yl] -pyrido [3,4-d] [1,3] oxazin- 4-one (200 mg) was dissolved in DMF (5 mL) , carbazaic acid methyl ester (190 mg) was added and the solution was stirred for 16 hours at room temperature. The reaction mixture was quenched with water and extracted with MTB- ether. The organic layer was washed 2x with water, washed with brine, dried over MgSC>4 and concentrated in vacuum. The residue was purified by column chromatography (silica 60, hexane/ethyl acetate = 1:1, then 1:2, Rf = 0.20 in hexane/ethyl acetate 1:2) to afford 43 mg of compound 2 of the present invention of the formula
Figure imgf000404_0001
as a white solid.
1H-NMR (DMSO-D6) δ (ppm) : 3.62 (3H, br s) , 7.62 (IH, s) , 7.67 (IH, dd, J = 8 Hz, 5 Hz) , 7.77 (IH, s) , 8.23 (IH, d, J
= 8 Hz) , 8.54 (IH, d, J = 5 Hz) , 9.47 (IH, s) , 10.49 (IH, s) , 10.92 (IH, s) .
Example 3: Preparation of N'- (3- { [5-bromo-2- (3-chloro- pyridin-2-yl ) -2H-pyrazole-3-carbonyl] -amino} -6-chloro-2- methyl-pyridine-4-carbonyl) -hydrazinecarboxylic acid methyl ester (3)
Step 1: preparation of ( 6-chloro-pyridin-3-yl) -carbamic acid tert-butyl ester
A mixture of 5-amino-2-chloropyridine (5.0 g) and di-tert- butyl dicarbonate (9.34 g) in dioxane (60 mL) was stirred for 2 hours under reflux. After cooling to room temperature, the reaction mixture was quenched with water and extracted with ethyl acetate. The organic layer was washed 5x with diluted hydrochloric acid, washed with saturated sodium bicarbonate, brine, dried over MgSO4 and concentrated in vacuum. The residue was washed with hexane to give 5.39 g of the title compound as a white solid. The combined acidic washings were re-extracted with MTB-ether. The organic layer was washed with brine, dried over MgSO4 and concentrated in vacuum. The residue was combined with the residue from the hexane washing and purified by column chromatography (silica 60, hexane/ethyl acetate 3:1, Rf = 0.40) to afford another 650 mg of the title compound of the formula
Figure imgf000405_0001
as a white solid.
1H-NMR (CDCl3, TMS) δ (ppm) : 1.52 (9H, s) , 6.60 (IH, s), 7.25 (IH, d, J = 8 Hz) , 7.95 - 7.97 (IH, br m) , 8.24 (IH, d, J = 3 Hz) .
Step 2: Preparation of 5- tert-butoxycarbonylamino-2-chloro- isonicotinic acid
A solution of ( 6-chloro-pyridin-3-yl) -carbamic acid tert- butyl ester (4.19 g) in diethyl ether (150 mL) was cooled to -78°C and N,N,N' ,N'-tetramethylethylendiamine (6.60 g) was added. After slow addition of n-butyl lithium solution (1.32 M in hexane, 41.6 mL) over a time period of 10 minutes, the mixture was allowed to warm up to -100C, stirred at this temperature for 2 hours and then was re- cooled to -78°C. The mixture was poured slowly into a stirred mixture of crushed dry ice in THF and stirred for 30 minutes. The mixture was concentrated on a rotary evaporator and water was added to the residue. The aqueous layer was washed 2x with MTB-ether and acidified with 6N hydrochloric acid to pH ~ 3. The formed precipitate was filtered off, washed with water, ethyl acetate and dried in vacuum to afford 2.46 g of the title compound of the formula
Figure imgf000406_0001
as beige solid.
1H-NMR (DMSO-D6) δ (ppm) : 1.48 (9H, s), 7.77 (IH, s), 9.13 (IH, s) , 10.13 (IH, s) .
Step 3: Preparation of 5-amino-2-chloroisonicotinic acid A suspension of 5- tert-butoxycarbonylamino-2-chloro- isonicotinic acid (2.46 g) in aqueous 2N potassium hydroxide solution (45 mL) was stirred at 90°C for 5 hours, After cooling to room temperature, the solution was acidified by slow addition of 6N hydrochloric acid. The formed precipitate was filtered off, washed with water, MTB-ether and hexane and dried in vacuum to afford 700 mg of the title compound of the formula
Figure imgf000407_0001
as beige solid .
1H-NMR ( DMSO-D6) δ (ppm) : 7 . 47 ( IH , s ) , 8 . 02 ( IH, s ) .
Step 4 : Preparation of S-amino-S-chloroisonicotinic acid methyl ester
5-Amino-2-chloroisonicotinic acid (1.72 g) was suspended in methanol (20 mL) and toluene (60 mL) was added. A solution of (trimethylsilyl ) diazomethane (2.0 M in diethyl ether, 6.5 mL) was added slowly to the suspension. Within 5 to 10 minutes after addition, the suspension turned into a solution. After 2 hours stirring at room temperature, the reaction mixture was quenched with water and extracted 3x with ethyl acetate. The combined organic layer was washed with saturated bicarbonate solution and brine, dried over MgSO4 and concentrated in vacuum.
The residue was purified by column chromatography (silica gel 60, chloroform/ethyl acetate = 20:1, Rf = 0.30 in chloroform/ethyl acetate = 3:1) to afford 1.50 g of the title compound of the formula
Figure imgf000408_0001
as a white solid.
1H-NMR (DMSO-D6) δ (ppm) : 3.83 (3H, s) , 6.77 (2H, s), 7.48 (IH, s) , 8.05 (IH, s) .
Step 5: Preparation of 3-amino-2-bromo-6-chloroisonicotinic acid methyl ester
5-Amino-3-chloroisonicotinic acid methyl ester (600 mg) was dissolved in DMF (5 mL) , N-bromosuccinimide (573 mg) was added and the solution was stirred for 3 hours at 800C and 24 hours at room temperature. The reaction mixture was diluted with MTB-ether and 3x washed with water, washed with brine, dried over MgSO4 and concentrated in vacuum. The residue was purified by column chromatography (silica 60, hexane/ethyl acetate = 10:1, Rf = 0.20) to afford 787 mg of the title compound of the formula
Figure imgf000408_0002
as a yellow solid. 1H-NMR (CDCl3, TMS) δ (ppm) : 3.93 (3H, s) , 6.23 (2H, br s) ,
7.67 (IH, s) . Step 6: Preparation of 3-amino-6-chloro-2- methylisonicotinic acid methyl ester
3-Amino-2-bromo-6-chloroisonicotinic acid methyl ester (500 mg) , potassium carbonate (829 mg) , tetrakis (triphenyl phosphine) palladium (0) and trimethylboroxine (276 mg) were suspended in dioxane (15 mL) . Water (1.5 mL) was added and the mixture was degassed using subseguent evaporation and flushing with nitrogen (5x) . The reaction mixture was stirred under reflux for 7 hours. After cooling to room temperature, the mixture was quenched with water and extracted 2x with ethyl acetate. The combined organic layer was washed with brine, dried over MgSCU and concentrated in vacuum. The residue was purified by column chromatography (silica 60, hexane/ ethyl acetate = 3 : 1, Rf = 0.25) to afford 100 mg of the title compound of the formula
Figure imgf000409_0001
as a yellow solid.
1H-NMR (CDCl3, TMS) δ (ppm) : 2.44 (3H, s), 3.92 (3H, s), 5.70 (2H, br s) , 7.57 (IH, s) .
Step 7: Preparation of 3-amino-6-chloro-2- methylisonicotinic acid 3-Amino-6-chloro-2-methylisonicotinic acid methyl ester (100 mg) was dissolved in methanol (2 iriL) and 2N aqueous sodium hydroxide solution (2 mL) was added. The reaction mixture was stirred under reflux for 2.5 hours . After cooling to room temperature, water and diethyl ether were added, the layers were separated and the aqueous layer was washed with diethyl ether. The aqueous layer was acidified by addition of 2N hydrochloric acid and the formed precipitate was 3x extracted with MTB-ether. The combined organic layer was washed with brine, dried over MgSO4 and concentrated in vacuum to afford 89 mg of the title compound of the formula
Figure imgf000410_0001
as a yellow solid. The crude product was used without further purification in the next step. 1H-NMR (DMSO-D6) δ (ppm) : 2.33 (3H, s), 7.40 (IH, s).
Step 8: Preparation of 2- [5-bromo-2- (3-chloro-pyridin-2-yl) -2E-pyrazol-3-yl]-6-chloro-8-methyl-pyrido[3, 4-d] [1, 3] oxazin-4-one A mixture of 5-bromo-2- (3-chloro-pyridin-2-yl) -2H-pyrazole -3-carboxylic acid "{-example 1, step 5) (144 mg) and thionyl chloride (105 μl) was stirred under reflux for 2 hours. Excess thionyl chloride was co-evaporated with dry toluene on a evaporator, the residue re-dissolved in dry acetonitrile (1.5 mL) and 3-amino-6-chloro-2- methylisonicotinic acid (89 mg) was added. The solution was stirred for 10 minutes at room temperature and triethylamine (65 μL) was added and stirred for 20 minutes, before a second portion of triethylamine (130 μL) was added. After the mixture was stirred for further 20 minutes at room temperature, methanesulfonyl chloride (45 μL) was added. After stirring for 48 hours at room temperature, the reaction mixture was quenched with water and extracted 3x with ethyl acetate. The combined organic layer was washed with brine, dried over MgSO4 and concentrated in vacuum. The residue was purified by column chromatography (silica 60, hexane/ethyl acetate = 3:1, Rf = 0.20) to afford 67 mg of the title compound of the formula
Figure imgf000411_0001
as a white solid.
1H-NMR (CDCl3, TMS) δ (ppm) : 2.10 (3H, s) , 7.28 (IH, s) , 7.53 (IH, dd, J = 8 Hz, 5 Hz) , 7.83 (IH, s), 8.00 (IH, dd, J = 8 Hz, 2 Hz) , 8.56 (IH, dd, J = 5 Hz, 2 Hz) .
Step 9: Preparation of N'- (3- { [5-bromo-2- (3-chloro-pyridin -2-yl) -2H-pyrazole-3-carbonyl] -amino} -6-chloro-2-methyl- pyridine-4-carbonyl ) -hydrazinecarboxylic acid methyl ester (3)
2- [5-Bromo-2- (3-chloro-pyridin-2-yl) -2H-pyrazol-3-yl] -6- chloro-8-methyl-pyrido [ 3, 4-d] [1, 3] oxazin-4-one (67 mg) was dissolved in DMF (4 mL) and carbazaic acid methyl ester (133 mg) was added. The solution was stirred for 20 hours at room temperature. The reaction mixture was quenched with water and extracted with MTB-ether. The organic layer was washed 4 x with water, washed with brine, dried over MgSO4 and concentrated in vacuum. The residue was purified by column chromatography (silica 60, chloroform/ethyl acetate = 1:1, Rf = 0.20) to afford 61 mg of compound 3 of the present invention of the formula
Figure imgf000412_0001
as a white solid.
1H-NMR (DMSO-D6) δ (ppm) : 2.35 (3H, s), 3.48-3.63 (3H, br m) , 7.36 (IH, s) , 7.39 (IH, s) , 7.62 (IH, dd, J= 8 Hz, 5 Hz), 8.18 (IH, dd, J = 8 Hz, 2 Hz), 8.50 (IH, dd, J = 5 Hz, 2 Hz), 9.41 (IH, s) , 10.38 (IH, s), 10.47 (IH, s) . Example 4: Preparation of N'- (2-broiαo-3- { [5-bromo-2- (3- chloro- pyridin-2-yl) -2H-pyra2ole-3-carbonyl] -amino}-6- chloro- pyridine-4-carbonyl) -hydrazinecarboxylic acid methyl ester (4)
Step 1: Preparation of 3-amino-2-bromo-6-chloroisonicotinic acid
3-Amino-2-bromo-6-chloroisonicotinic acid methyl ester (260 mg) (example 3, step 5) was dissolved in methanol (2 mL) , 2N aqueous sodium hydroxide solution (2 mL) was added and the reaction mixture was stirred for 2 hours at reflux. After cooling to room temperature, diethyl ether and water were added and the layers were separated. The aqueous layer was washed with diethyl ether and acidified by addition of 2N hydrochloric acid. The formed precipitate was extracted with MTB-ether (3x) , the combined organic layer was washed with brine, dried over MgSCU and concentrated in vacuum to afford 246 mg of
Figure imgf000413_0001
as a yellow solid.
1H-NMR (DMSO-D6) δ (ppm) : 6.82 (2H, br s) , 7.61 (IH, s).
Step 2: Preparation of 8-bromo-2- [5-bromo-2- (3-chloro- pyridin-2-yl) -2ff-pyrazol-3-yl] -6-chloro-pyrido [3, 4-d] [1, 3] oxazin-4-one
A mixture of 5-bromo-2- (3-chloro-pyridin-2-yl) -2H-pyrazole -3-carboxylic acid (example 1, step 5) (1.20 g) and thionyl chloride (870 μl) was stirred under reflux for 2 hours. Excess thionyl chloride was co-evaporated with dry toluene on a evaporator, the residue re-dissolved in dry acetonitrile (12 mL) and 3-amino-2-bromo-6- chloroisonicotinic acid (750 mg) was added. The solution was stirred for 10 minutes at room temperature and triethylamine (560 μL) was added and stirred for 20 minutes, before a second portion of triethylamine (1.20 mL) was added. After the mixture was stirred for further 20 minutes at room temperature, methanesulfonyl chloride (340 μL) was added. After stirring for 20 hours at room temperature, the reaction mixture was quenched by slow addition of water. The precipitate was filtered off, washed with water/acetonitrile (1 : 2), acetonitrile and diethyl ether and dried in vacuum to afford 598 mg of the title compound of the formula
Figure imgf000414_0001
as beige solid. 1H-NMR (CDCl3, TMS) δ (ppm) : 7.32 (IH, s) , 7.50 (IH, dd, J = 8 Hz, 5 Hz) , 7.94 (IH, s) , 8.00 (IH, d, J = 8 Hz) , 8.55 (IH, d, J = 5 Hz) .
Step 3: Preparation of N'- (2-bromo-3- { [5-bromo-2- (3-chloro -pyridin-2-yl) -2H-pyrazole-3-carbonyl] -amino} -6-chloro- pyridine-4-carbonyl) -hydrazinecarboxylic acid methyl ester (4) 8-Bromo-2- [5-bromo-2- (3-chloro-pyridin-2-yl) -2H-pyrazol -3- yl] -6-chloro-pyrido [3, 4-d] [1, 3] oxazin-4-one (400 mg) was dissolved in DMF (12 mL) and carbazaic acid methyl ester (696 mg) was added. The solution was stirred for 22 hours at room temperature. The reaction mixture was quenched with water and extracted with MTB-ether. The organic layer was washed 3x with water, brine, dried over MgSO4 and concentrated in vacuum. The residue was purified by column chromatography (silica 60, chloroform/ethyl acetate = 1:1, Rf = 0.20) to afford 330 mg of compound 4 of the present invention of the formula
Figure imgf000415_0001
as a white solid. 1H-NMR (DMSO-D5) δ (ppm) : 3.45-3.63 (3H, br m) , 7.42 (IH, s) , 7.59-7.63 (2H, m) , 8.17 (IH, dd, J = 8 Hz, 2 Hz) , 8.51 (IH, dd, J = 5 Hz, 2 Hz) , 9.47 (IH, br s) , 10.44 (IH, s) , 10.76 (IH, s) .
Example 5: Preparation of N'- (2 , 6-dibromo-3- { [5-bromo-2- ( 3-chloro-pyridin-2-yl) -2H-pyrazole-3-carbonyl] -amino } - pyridine-4-carbonyl) -hydrazinecarboxylic acid methyl ester (5)
Step 1; Preparation of pyridin-3-yl-carbaπιic acid tert- butyl ester
3-Aminopyridine (20.0 g) was dissolved in tert-butanol (300 mL), di- tert-butyl dicarbonate (52.0 g) was added and the solution was stirred at 500C for 5 hours, then for 12 hours at room temperature and another 7 hours at 500C. The solvent was evaporated on a rotary evaporator and the residue was dissolved in ethyl acetate. The organic layer was 3x washed with water, washed with brine, dried over
MgSO4 and concentrated in vacuum. The residue was purified 2x by column chromatography (silica 60, hexane/ethyl acetate = 1:1, then 1:2, Rf = 0.15) to afford 6.20 g of the title compound of the formula Y.
Figure imgf000417_0001
as a yellow solid.
1H-NMR (CDCl3, TMS) δ (ppm) : 1.53 (9H, s), 6.71 (IH, s), 7.24 (IH, dd, J = 8 Hz, 5Hz), 7.99 (IH, d, J = 8 Hz), 8.28 (IH, d, J = 5 Hz), 8.45 (IH, d, J = 2 Hz) .
Step 2: Preparation of 3- tert-butoxycarbonylamino- isonicotinic acid
Pyridin-3-yl-carbamic acid tert-butyl ester (6.20 g) was dissolved in anhydrous diethyl ether (260 rtiL) , cooled to - 78°C and N,N,N' ,N'-tetramethylethylendiamine (14.4 mL) was added. A solution of n-butyl lithium (1.6 M in hexane, 60 mL) was added slowly over a time period of 10 minutes. After the addition of the reagent was completed, the reaction mixture was allowed to warm to -100C and stirred at this temperature for 2 hours. The reaction mixture was then re-cooled to -78°C and slowly poured on a stirred mixture of dry ice in diethyl ether. After stirring for 30minutes, water was added to the reaction mixture and the layers were separated after complete dissolution of solid materials. The aqueous layer was washed 2x with diethyl ether and the pH-value of the aqueous layer was adjusted to 5-6. The organic layer was extracted 2x with MTB-ether. The combined organic layer was washed with a small amount of brine, dried over MgSO4 and concentrated in vacuum. The residue was washed with hexane to remove oily by-products and dried in vacuum to afford 1.19 g of the title compound as beige solid. The aqueous washing was concentrated on a rotary evaporator to approx. 50 mL, inorganic salts were filtered off and MTB-ether was added to the mother liquor. 6N Hydrochloric acid was slowly added into the well-stirred mixture until the pH-value was adjusted to ~3. The layers were separated, the aqueous layer was washed 2x with MTB- ether and 2x with chloroform. The combined organic layer was dried over MgSO4 and dried in vacuum to give another 2.03 g of beige solid. Together with the first organic extract, 3.22 g of the title compound of the formula
Figure imgf000418_0001
were isolated as beige solid. The compound was used in the next step without further purification.
1H-NMR (DMSO-D6) δ (ppm) : 1.47 (9H, s), 7.74 (IH, d, J = 5
Hz), 8.34 (IH, d, J = 5 Hz), 9.35 (IH, s), 10.07 (IH, s).
Step 3: Preparation of 3-aminoisonicotinic acid
3- tert-Butoxycarbonylamino-isonicotinic acid (450 mg) was dissolved in methanol (8 mL) and 6N hydrochloric acid (5 mL) was added to the solution. The resulting suspension was ■ starred under reflux for 2.5 hours, cooled to room temperature and washed 3x with chloroform. The aqueous layer was adjusted to pH~14 by addition of 2N sodium hydroxide solution, washed 3x with chloroform and adjusted again to pH~3 by addition of 2N hydrochloric acid. The aqueous layer was concentrated on a rotary evaporator to complete dryness and the residue was extracted with hot ethanol . The ethanol extract was filtered to remove insoluble material and concentrated in vacuum to afford 262 mg of the title compound of formula
Figure imgf000419_0001
as a yellow solid. The compound was used in the next step without further purification.
1H-NMR (DMSO-D6) δ (ppm) : 7.78 (IH, d, J = 5 Hz), 7.84 (IH, d, J = 5 Hz) , 8.30 (IH, s) .
Step 4: Preparation of 3-amino-2, 6-dibromoisonicotinic acid 3-Arαinoisonicotinic acid (260 mg) was dissolved in DMF (10 mL) N-bromosuccinimide (320 mg) was added and the reaction mixture was stirred at room temperature for 1 hour before another portion of N-bromosuccinimide (320 mg) was added. After stirring for 3 hours at room temperature, the reaction mixture was quenched with water. 2N Sodium hydroxide solution was added, the aqueous solution was washed 2x with diethyl ether and adjusted to pH~2 by addition of 6N hydrochloric acid. The aqueous layer was extracted 3x with MTB-ether, the combined organic layer was washed with brine, dried over MgSO4 and concentrated in vacuum to afford 283 mg of the title compound of the formula
Figure imgf000420_0001
as a yellow-orange solid. The compound' was contaminated with ca.10% impurities and was used without further purification in the next step. 1H-NMR (CDCl3, TMS) δ (ppm) : 6.16 (2H, br s) , 7.61 (IH, s).
Step 5: Preparation of 6, 8-dibromo-2- [5-bromo-2- (3-chloro- pyridin-2-yl) -2ff-pyrazol-3-yl] -pyrido [3,4-d] [1,3] oxazin-4- one A mixture of 5-bromo-2- (3-chloro-pyridin-2-yl) -2H- pyrazole-3-carboxylic acid (example 1, step 5) (242 mg) and thionyl chloride (180 μl) was stirred under reflux for 2 hours. Excess thionyl chloride was co-evaporated with dry toluene on a evaporator, the residue re-dissolved in dry acetonitrile (3 mL) and 3-amino-2, 6-dibromoisonicotinic acid (282 mg) was added. The solution was stirred for 10 minutes at room temperature and triethylamine (110 μL) was added and stirred for 20 minutes, before a second portion of triethylamine (220 μL) was added. After the mixture was stirred for further 20 minutes at room temperature, methanesulfonyl chloride (75 μL) was added. After stirring for 18 hours at room temperature, the reaction mixture was quenched by slow addition of water. The precipitate was filtered off, washed with water/acetonitrile (1:2), acetonitrile and diethyl ether and dried in vacuum to afford 153 mg of the title compound of the formula
Figure imgf000421_0001
as beige solid.
1H-NMR (CDCl3, TMS) δ (ppm) : 7.32 (IH, s), 7.50 (IH, dd, J = 8 Hz, 5 Hz), 8.00 (IH, d, J = 8 Hz), 8.09 (IH, s), 8.56 (IH, d, J = 5 Hz) .
Step 6: Preparation of N'- (2, 6-dibromo-3- { [5-bromo-2- (3- chloro-pyridin-2-yl ) -2H-pyrazole-3-carbonyl] -amino }- pyridine-4- carbonyl) -hydrazinecarboxylic acid methyl ester (5) 6, 8-Dibromo-2- [5-bromo-2- (3-chloro-pyridin-2-yl) -2H- pyrazol-3-yl] -pyrido [3, 4-d] [1, 3] oxazin-4-one (153 mg) was dissolved in DMF (7 mL) and carbazaic acid methyl ester (240 mg) was added. The solution was stirred for 19 hours at room temperature. The reaction mixture was quenched with water and extracted with MTB-ether. The organic layer was washed 3x with water, brine, dried over MgSO4 and concentrated in vacuum. The residue was purified by column chromatography (silica 60, chloroform/ethyl acetate = 1:1, Rf = 0.20) to afford 128 mg of compound 5 of the present invention of the formula
Figure imgf000422_0001
as beige solid. 1H-NMR (DMSO-D6) δ (ppm) : 3.49-3.62 (3H, m) , 7.42 (IH, s), 7.61 (IH, dd, J= 8 Hz, 5 Hz), 7.70 (IH, s) , 8.17 (IH, d, J = 8 Hz), 8.50 (IH, d, J = 5 Hz), 9.46 (IH, br s), 10.44 (IH, s) , 10.75 (IH, s) .
Example 6: Preparation of N'- (4- { [5-bromo-2- (3-chloro- pyridin -2-yl) -2H-pyrazole-3-carbonyl] -amino}-5-chloro- pyridine-3- carbonyl) -hydrazinecarboxylic acid methyl ester (6)
Step 1: Preparation of (3-chloro-pyridin-4-yl) -carbamic acid fcert-butyl ester 3-Chloro-isonicotinic acid (3.0 g) was dissolved in tert- butanol (80 rtiL) , diphenyl phosphoryl azide (5.24 g) and triethylamine (2.7 mL) were added and the reaction mixture was stirred at 1000C for 5.5 h. After cooling to room temperature, the reaction mixture was concentrated in vacuum and the residue was dissolved in ethyl acetate and water. The layers were separated and the aqueous layer was 2x extracted with ethyl acetate, the combined organic layer was washed with brine, dried over magnesium sulfate and concentrated in vacuum. The residue was purified by column chromatography (silica 60, hexane/ethyl acetate 3:1, Rf =
0.30) to afford 2.74 g of the title compound of the formula
Figure imgf000423_0001
as a white solid. 1H-NMR (CDCl3, TMS) δ (ppm) : 1.55 (9H, s) , 7.18 (IH, br s) , 8.15 (IH, d, J = 6 Hz), 8.36 (IH, d, J = 6 Hz), 8.46 (IH, s) .
Step 2 : Preparation of 4 - tert-butoxycarbonylamino-5-chloro- nicotinic acid
( 3-Chloro-pyridin-4 -yl ) -carbamic acid tert-butyl ester
( 1 . 50 g ) was dissolved in dry diethyl ether ( 35 mL ) ,
W, W, W , W -tertamethylenethylendiamine ( 2 . 35 mL ) was added and the reaction mixture was cooled in a dry ice/acetone cool bath to -78°C. n-Butyl lithium (9.9 mL, 1.59M in hexane) was added to the suspension, the cool bath was replaced by a sodium chloride/ice mixture and the reaction mixture was stirred at -100C for 1.5 h. The suspension was slowly poured on crushed dry ice (2.0 g) in dry diethyl ether (20 mL) and stirred for 1 h. Water was added and the pH was adjusted to -12 by addition of 2 N sodium hydroxide solution. The aqueous layer was washed 2x with MTB-ether, 2 M hydrochloric acid was added to the aqueous layer and the pH was adjusted to ~2 and the aqueous layer was 3x extracted with ethyl acetate. The combined organic layer was washed with brine, dried over magnesium sulfate and concentrated in vacuum to afford 1.03 g of the title compound of the formula
Figure imgf000424_0001
as a beige solid. The crude product contained -30% valeric acid and was used without further purification in the next step. 1H-NMR (DMSO-D6) δ (ppm) : 1.44 (9H, s), 8.72 (IH, s), 8.74 (IH, s), 9.49 (IH, s), 13.29 (IH, br s).
Step 3: Preparation of 4-amino-5-chloro-nicotinic acid 4-tert-Butoxycarbonylamino-5-chloro-nicotinic acid (1.03 g, crude product from step 2 in a -3:1 mixture with valeric acid) was dissolved in methanol (10 mL) , 5 M hydrochloric acid (10 mL) was added and the reaction mixture was stirred for 1.5 h under gentle reflux. After cooling to room temperature, the mixture was concentrated in vacuum, the residue was dissolved in water and the mixture was adjusted to pH ~ 12 by addition of 2 N sodium hydroxide solution. The aqueous layer was washed 2x with a mixture of MTB- ether/hexane (1:1), then 5 M hydrochloric acid was added and the aqueous layer was adjusted to pH ~ 2. The aqueous layer was 2x washed with ethyl acetate and the aqueous layer was then concentrated in vacuum to dryness. The residue was 3x dissolved in methanol/toluene and co- evaporated to dryness to remove traces of water. The residue was suspended in methanol (50 mL) , stirred under reflux for 30 ,InIn cooled to room temperature and insoluble salts were removed by filtration. The filtrate was concentrated and dried in vacuum to afford 1.59 g of a yellow solid containing the title compound of the formula
Figure imgf000425_0001
The crude product still contained inorganic salts and was used in the next step without further purification. 1H-NMR ( DMSO-D6) δ (ppm) : 8 . 60- 9 . 03 ( 2H , br m) , 8 . 71 ( IH , s ) , 8 . 73 ( IH , s ) .
Step 4: Preparation of 2- [5-bromo-2- (3-chloro-pyridin-2-yl) -2H-pyrazol-3-yl] -8-chloro- pyrido [4 , 3-d] [1, 3] oxazin-4-one 5-Bromo-2- (3-chloro-pyridin-2-yl) -2H-pyrazole-3-carboxylic acid (example 1, step 5) (696 mg) was suspended in dry toluene (20 πiL) , oxalyl chloride (580 μL) and 3 drops of dry DMF were added (gas evolution) and the reaction mixture was stirred for 1 h at room temperature. The mixture was concentrated in vacuum and excess oxalyl chloride was removed by co-evaporation with dry toluene (3x) . The residue was dissolved in dry acetonitrile (20 mL) and 4- amino-5-chloro-nicotinic acid (crude mixture from the above step 3, 1.0 g) and triethylamine (320 μL) were added. The reaction mixture was stirred for 30 minutes, before a second portion of triethylamine (640 μL) was added. After the mixture was stirred for further 20 minutes at room temperature, methanesulfonyl chloride (195 μL) was added. After stirring for 4 h at room temperature, the reaction mixture was quenched by addition of water (10 mL) . The precipitate was filtered off, washed with water/acetonitrile (1:2), acetonitrile and diethyl ether and dried in vacuum to afford 250 mg of the title compound of the formula
Figure imgf000427_0001
as a beige solid.
1H-NMR (CDCl3, TMS) δ (ppm) : 7.36 (IH, s) , 7.50 (IH, dd, J = 8 Hz, 5 Hz) , 7.99 (IH, dd, J = Q Hz, 2 Hz) , 8.55 (IH, dd,
J = 5 Hz, 2 Hz) , 8.84 (IH, s) , 9.24 (IH, s) .
Step 5: Preparation of N'- (4- { [5-bromo-2- (3-chloro-pyridin- 2-yl) -2H-pyrazole-3-carbonyl] -amino} -S-chloro-pyridine-S- carbonyl) -hydrazinecarboxylic acid methyl ester (6)
2- [5-Bromo-2- (3-chloro-pyridin-2-yl) -2H-pyrazol-3-yl] -8- chloro-pyrido [4 , 3-d] [1, 3] oxazin- 4-one (150 mg) was dissolved in DMF (10 mL) and carbazaic acid methyl ester (154 mg) was added. The solution was stirred for 2 h at room temperature before it was quenched with water. The mixture was 2x extracted with ethyl acetate, the combined organic layer was 3x washed with water, washed with brine, dried over magnesium sulfate and concentrated in vacuum. The residue was purified by column chromatography (silica 60, chloroform/methanol = 20:1, then 10:1, Rf = 0.15 in chloroform/methanol = 10:1) to afford 99 mg of compound (6) of the present invention of the formula Br
irVvS: C1 (6)
HI1I-*" CO2Me as a white solid
1H-NMR (DMSO-D6) δ (ppm) : 3.46-3.65 (3H, m) , 7.45 (IH, s), 7.61 (IH, dd, J = 8 Hz, 5 Hz) , 8.17 (IH, d, J = 8 Hz), 8.51 (IH, d, J = 5 Hz) , 8.64 (IH, s) , 8.86 (IH, s), 9.40 (IH, br s), 10.44 (IH, s) , 10.81 (IH, s) .
Example 7: Preparation of [N'- (3- { [5-bromo-2- (3-chloro- pyridin-2-yl) -2ff-pyrazole- 3-carbonyl] -amino} -6-chloro- 4- methyl-pyridine-2-carbonyl) -hydrazinecarboxylic acid methyl ester (7)
Step 1: Preparation of 3-amino-6-chloro-2-iodo-4- methylpyridine 5-Amino-2-chloro-4-methylpyridine (1.35 g) was dissolved in DMF (20 mL) , N-iodosuccinimide (2.59 g) was added and the reaction mixture was stirred at room temperature for 12 hours. Ethyl acetate was added and the organic layer was washed 3x with water, washed with brine, dried over MgSO4 and concentrated in vacuum. The residue was purified by column chromatography (silica 60, hexane/ethyl acetate = 3:1, Rf = 0.30) to afford 1.38 g of the title compound of
Figure imgf000429_0001
as an orange solid.
1H-NMR (CDCl3, TMS) δ (ppm) : 2.21 (3H, s) , 4.06 (2H, br s), 6.95 (IH, s) .
Step 2: Preparation of 3-amino-6-chloro-2- (2-furanyl) -4- methylpyridine
3-Amino-6-chloro-2-iodo-4-methylpyridine (1.38 g) , 2- furanboronic acid (861 mg) , and sodium carbonate (815 mg) were suspended in a solvent mixture consistent of toluene (19 mL) , THF (19 mL) and water (6 mL) . The mixture was degassed using subsequent evaporation and flushing with nitrogen (5x) and tetrakis (triphenylphosphine) palladium(O) (658 mg) was added. The reaction mixture was stirred at 90°C for 5 hours and 12 hours at room temperature. After addition of another portion of 2-furanboronic acid (430 mg) and tetrakis (triphenyl phosphine) palladium(O) (132 mg) , the mixture was stirred again for 12 hours at 90°C. After 12 hours stirring at room temperature, the reaction mixture was quenched with water and extracted 2x with ethyl acetate. The combined organic layer was washed with brine, dried over MgSθ4 and concentrated in vacuum. The residue was purified by column chromatography (silica 60, hexane/ethyl acetate = 4:1, Rf = 0.25) to afford 929 mg of the title compound of the formula
Figure imgf000430_0001
as an orange solid. 1H-NMR (CDCl3, TMS) δ (ppm) : 2.20 (3H, s), 4.65 (2H, br s), 6.56 (IH, dd, J = 4 Hz, 2 Hz), 6.94 (IH, s), 7.07 (IH, dd, J = 4 Hz, 1 Hz), 7.54 (IH, dd, J= 2 Hz, 1 Hz).
Step 3: Preparation of 3-amino-6-chloro-4-methyl-pyridine- 2- carboxylic acid
3-Amino-6-chloro-2- (2-furanyl) -4-methylpyridine (400 mg) was dissolved in acetone (10 mL) and cooled in an ice bath to 00C. A solution prepared of potassium permanganate (909 mg) in water (15 mL) was added drop wise to this solution. After complete addition, the reaction mixture was allowed to warm to room temperature and stirred for 2 hours. The mixture was cooled again to 00C and a second portion of potassium permanganate (600 mg) in water (10 mL) was added and the cool bath removed. After stirring for 2 hours, the reaction mixture was filtered through a pad of celite, the filter cake was washed carefully with water, methanol and ethyl acetate and concentrated to approx. 10 mL on a rotary evaporator. 2N Sodium hydroxide solution was added to adjust the pH-value to -12 and the aqueous layer was washed 2x with MTB-ether. The aqueous layer was then adjusted to pH~2 by addition of 6N hydrochloric acid and extracted 3x with MTB-ether. The combined organic layer was washed with brine, dried over MgSO4 and concentrated in vacuum to afford 262 mg of the title compound of the formula
Figure imgf000431_0001
as a orange-brown solid.
1H-NMR (CDCl3, TMS) δ (ppm) : 2.24 (3H, d, J = 1 Hz) , 5.94 (2H, br s) , 7.21 (IH, d, J = 1 Hz) .
Step 4: Preparation of 2- [5-bromo-2- (3-chloro-pyridin-2-yl) -2H-pyrazol-3-yl] -6-chloro-8-methyl-pyrido [3, 2-d] [1,3] oxazin-4-one A mixture of 5-bromo-2- (3-chloro-pyridin-2-yl) -2H-pyrazole -3-carboxylic acid (example 1, step 5) (413 mg) and thionyl chloride (300 μl) was stirred under reflux for 2 hours. Excess thionyl chloride was co-evaporated with dry toluene on a evaporator, the residue re-dissolved in dry acetonitrile (5 iriL) and 3-amino-6-chloro-4-methyl-pyridine- 2-carboxylic acid (255 mg) was added. The solution was stirred for 15 minutes at room temperature and triethylamine (190 μL) was added and stirred for 30 minutes, before a second portion of triethylamine (380 μL) was added, After the mixture was stirred for further 30 minutes at room temperature, methanesulfonyl chloride (120 μL) was added. After stirring for 20 hours at room temperature, the reaction mixture was quenched by slow addition of water. The precipitate was filtered off, washed with water/acetonitrile (1:2), acetonitrile and diethyl ether and dried in vacuum to afford 112 mg of the title compound of the formula
Figure imgf000432_0001
as beige solid.
1H-NMR (CDCl3, TMS) δ (ppm) : 1.89 (3H, d, J = 1 Hz), 7.29 (IH, s), 7.47 (IH, d, J = 1 Hz), 7.50 (IH, dd, J = 8 Hz, 5
Hz), 7.98 (IH, dd, J = 8 Hz, 2 Hz), 8.56 (IH, dd, J = 5 Hz, 2 Hz) .
Step 5: Preparation of (N'- (3- { [5-bromo-2- (3-chloro-pyridin -2-yl) -2H-pyrazole-3-carbonyl] -amino}-6-chloro-4-methyl- pyridine-2-carbonyl) -hydrazinecarboxylic acid methyl ester m_
2- [5-Bromo-2- (3-chloro-pyridin-2-yl) -2H-pyrazol-3-yl] -6- chloro-8-methyl-pyrido [3, 2-d] [ 1, 3] oxazin-4-one (112 mg) was dissolved in DMF (7 mL) and carbazaic acid methyl ester (223 mg) was added. The solution was stirred for 3.5 hours, dried over MgSO4 and concentrated in vacuum. The residue was purified by column chromatography (silica 60, chloroform/ethyl acetate = 3:1, Rf = 0.25) to afford 113 mg of compound 7 of the present invention of the formula
Figure imgf000433_0001
as a white solid.
1H-NMR (DMSO-D6) δ (ppm) : 2.19 (3H, s), 3.50-3.61 (3H, br m) , 7.42 (IH, s), 7.62 (IH, dd, J = 8 Hz, 5 Hz), 7.73 (IH, s), 8.18 (IH, dd, J = 8 Hz, 2 Hz), 8.50 (IH, dd, J = 5 Hz, 2 Hz), 9.27 (IH, br s) , 10.41 (IH, s) , 10.56 (IH, s).
Alternative preparation of N'- (3- { [5-bromo-2- (3~chloro- pyridin-2-yl) -2#-pyrazole-3-carbonyl] -amino} -6-chloro-4- methyl-pyridine-2-carbonyl) -hydrazinecarboxylic acid methyl ester (7)
Step 1: Preparation of ( 6-chloro-pyridin-3-yl) -carbamic acid tert-butyl ester
6-Chloro-pyridin-3-ylamine (10.0 g) were dissolved in tert- butanol (140 mL) , di-tert-butyl dicarbonate (18.7 g) were added and the solution was stirred at 500C for 4 h. Di- tert-butyl dicarbonate (3.40 g) was added and the reaction mixture was stirred for another 8 h at 5O0C. Most of the solvent was removed in vacuum and the residue was dissolved in ethyl acetate and washed 3x with water, washed with brine, dried over magnesium sulfate and concentrated in vacuum. The residue was purified by column chromatography (silica 60, chloroform/ethyl acetate 10:1, Rf = 0.30) to afford 16.5 g of the title compound of the formula
Figure imgf000434_0001
as a white solid .
1H-NMR (CDCl3, TMS) δ (ppm) : 1.52 (9H, s), 6.54 (IH, br s), 7.27 (IH, d, J = 3 Hz), 7.96 (IH, s), 8.23 (IH, d, J = 3 Hz) .
Step 2: Preparation of ( 6-chloro-4-methyl-pyridin-3-yl) - carbamic acid tert-butyl ester
( 6-Chloro-pyridin-3-yl) -carbamic acid tert-butyl ester (14.11 g) was dissolved in dry diethyl ether (310 mL) ,
N,N,N' ,W-tetramethyl-ethylene-1, 2-diamine (23.1 mL) was added. The solution was cooled to -780C, .n-butyl lithium
(97 mL, 1.59 M in hexane) was added, the cool bath replaced by an ice/sodium chloride cool bath and the suspension was stirred for 2 h at -100C. The suspension was cooled again to -78°C and methyl iodide (5.8 mL) was added slowly. The cool bath was removed and the reaction was quenched after 1 h by addition of water. Ethyl acetate was added and the mixture was neutralized by addition of 2 M hydrochloric acid. The layers were separated and the aqueous layer was extracted 2x with ethyl acetate, the combined organic layer was washed with brine, dried over magnesium sulfate and concentrated in vacuum. The residue was purified by column chromatography (silica 60, hexane/ethyl acetate 5:1, Rf = 0.10) to afford 4.24 g of the title compound of the formula
Figure imgf000435_0001
as a yellow solid.
1H-NMR (CDCl3, TMS) δ (ppm) : 1.52 (9H, s), 2.26 (3H, s), 6.21 (IH, s), 7.13 (IH, s) , 8.69 (IH, s).
Step 3: Preparation of (6-chloro-4-methyl-l-oxy-pyridin-3- yl)- carbamic acid tert-butyl ester
( 6-Chloro-4-methyl-pyridin-3-yl) -carbamic acid tert-butyl ester (4.24 g) was dissolved in chloroform (40 mL) , 3- chloroperoxybenzoic acid (5.87 g, 77%) was added and the solution was stirred at room temperature for 21 h. A second portion of 3-chloroperoxybenzoic acid (1.17 g) was added and the reaction mixture was stirred for 5 h at room temperature. Chloroform was added until complete dissolution of the solids and the organic phase was washed with 2 N sodium hydroxide solution. The aqueous washing was Ix re-extracted with chloroform and the combined organic layer was washed again with 2 N sodium hydroxide solution, water, brine, dried over magnesium sulfate and concentrated in vacuum to afford 4.40 g of the title compound of the formula
Figure imgf000436_0001
as a white solid. The crude product was used without further purification in the next step.
1H-NMR (CDCl3, TMS) δ (ppm) : 1.52 (9H, s) , 2.24 (3H, s), 6.24 (IH, s), 7.22 (IH, s) , 9.13 (IH, s) .
Step 3: Preparation of (6-chloro-2-cyano-4-methyl-pyridin- 3-yl) -carbamic acid tert-butyl ester
( 6-Chloro-4-methyl-l-oxy-pyridin-3-yl) -carbamic acid tert- butyl ester (4.40 g) was suspended in dry acetonitrile (50 mL) , trimethylsilyl cyanide (7.2 mL) and triethyl amine
(5.37 mL) were added and the reaction mixture was stirred under reflux for 2 h. After standing for 15 h at room temperature, trimethylsilyl cyanide (4.4 inL) and triethyl amine (3.65 mL) were added and the reaction- mixture was stirred for another 4 h at reflux. Water and 2 N sodium hydroxide solution were added after cooling to room temperature and the mixture was 3x extracted with ethyl acetate. The combined organic layer was washed with brine, dried over magnesium sulfate and concentrated in vacuum. The residue was purified by column chromatography (silica 60, hexane/ethyl acetate = 5:1, then 4:1, Rf = 0.20 in hexane/ethyl acetate = 4.1) to afford 3.72 g of the title compound of the formula
Figure imgf000437_0001
as a yellow solid.
1H-NMR (CDCl3, TMS) δ (ppm) : 1.52 (9H, s), 2.36 (3H, s), 6.43 (IH, s) , 7.42 (IH, s) .
Step 4: Preparation of 3-amino-6-chloro-4-methyl-pyridine- 2-carboxylic acid
( 6-Chloro-2-cyano-4-methyl-pyridin-3-yl) -carbamic acid tert-butyl ester (3.72 g) was dissolved in concentrated sulfuric acid (19 mL) and stirred for 1 h at 1000C. The reaction mixture was cooled to room temperature and water (19 mL) was slowly added. The reaction mixture was warmed again to 1000C and stirred at this temperature for 2 h. Water was added after cooling to room temperature, the mixture was cooled in an ice bath and the pH was adjusted to ~14 by slow addition of solid sodium hydroxide. The aqueous solution was washed 2x with MTB-ether, the aqueous layer was then adjusted to pH ~2 by addition of 5 M hydrochloric acid and extracted 3x with ethyl acetate. The combined organic layer was washed with brine, dried over magnesium sulfate and concentrated in vacuum to afford 2.25 g of the title compound of the formula
Figure imgf000438_0001
as a beige solid.
1H-NMR (CDGl3, TMS) δ (ppm) : 2.24 (3H, s), 5.96 (2H, s), 7.20 (IH, s), 10.69 (IH, br s) .
Step 5: Preparation of 2- [5-bromo-2- (3-chloro-pyridin-2- yl) - 2H-pyrazol-3-yl] -6-chloro-8-methyl-pyrido [3,2- d] [1, 3] oxazin-4-one
5-Bromo-2- (3-chloro-pyridin-2-yl) -2H-pyrazole-3-carboxylic acid (example 1, step 5) (3.65 g) was suspended in dry toluene (50 mL) , oxalyl chloride (3.10 mL) and 10 drops of dry DMF were added (gas evolution) and the reaction mixture was stirred for 1 h at room temperature. The mixture was concentrated in vacuum and excess oxalyl chloride was removed by co-evaporation with dry toluene (3x) . The residue was dissolved in dry acetonitrile (20 mL) and added to a suspension of 3-amino-6-chloro-4-methyl-pyridine- 2- carboxylic acid (2.25 g) in acetonitrile (30 mL) . Triethylamine (1.7 mL) ) was added and the reaction mixture was stirred for 20 minutes, before a second portion of triethylamine (3.4 mL) was added. After the mixture was stirred for further 50 minutes at room temperature, methanesulfonyl chloride (1.03 mL) was added. After stirring for 18 hours at room temperature, the reaction mixture was concentrated to ~25 mL and water (20 mL) was added. The precipitate was filtered off, washed with water/acetonitrile (1:2), acetonitrile and diethyl ether and dried in vacuum to afford 3.97 g of the title compound of the formula
Figure imgf000439_0001
as a yellow solid.
1H-NMR (CDCl3, TMS) δ (ppm) : 1.89 (3H, d) , 7.29 (IH, s), 7.47 (IH, s), 7.50 (IH, dd, J = 8 Hz, 5 Hz), 7.98 (IH, dd, J = 8 Hz, 2 Hz), 8.56 (IH, dd, J = 5 Hz, 2 Hz). Step 6: Preparation of (N'- (3- { [5-bromo-2- (3-chloro- pyridin- 2-yl) -2E-pyrazole-3-carbonyl] -amino} -6-chloro-4- methyl- pyridine-2-carbonyl) -hydrazinecarboxylie acid methyl ester (7) 2- [5-Bromo-2- (3-chloro-pyridin-2-yl) -2#-pyrazol-3-yl] -6- chloro-8-methyl-pyrido [3, 2-d] f 1, 3] oxazin-4-one (500 mg) was dissolved in DMF (28 mL) acarbazaic acid methyl ester
(994 mg) was added. The solution was stirred for 3.5 h at room temperature before it was quenched with water. The mixture was 2x extracted with ethyl acetate, the combined organic layer was 3x washed with water, washed with brine, dried over magnesium sulfate and concentrated in vacuum. The residue was purified by column chromatography (silica 60, chloroform/ethyl acetate = 3:1, Rf = 0.25) to afford 541 mg of the compound (7) of the present invention of the formula
Figure imgf000440_0001
as a white solid.
1H-NMR (DMSO-D6) δ (ppm) : 2.19 (3H, s) , 3.50-3.61 (3H, br m) , 7.42 (IH, s), 7.62" (IH, -dd, J = 8 Hz, 5 Hz) , 7.73 (IH, s) , 8.18 (IH, dd, J = 8 Hz, 2 Hz) , 8.50 (IH, dd, J = 5 Hz, 2 Hz) , 9.27 (IH, br s) , 10.41 (IH, s) , 10.56 (IH, s) . Example 8: Preparation of N'- (3- { [5-bromo-2- (3-chloro- pyridin -2-yl) -2H-pyrazole-3-carbonyl] -amino} -6-chloro-4- methyl- pyridine-2-carbonyl) -N-methyl-hydrazinecarboxylic acid methyl ester (8)
Step 1: Preparation of N-methyl-hydrazine-carboxylic acid methyl ester
Monomethylhydrazine (10.6 itiL) was dissolved in methanol (50 inL) and sodium hydroxide (8.0 g) was added. The suspension was cooled with an ice bath and methyl chloroformate (15.4 mL) was added drop wise (violent reaction!), the ice bath was removed and the suspension was stirred for 1 hour at room temperature. The white precipitate was filtered off, washed with methanol and the filtrate was concentrated in vacuum. The residue was purified by distillation (50-80 °C /15 mmHg) to afford 13.4 g of the title compound of the formula
MeO2C
N-NH2 Me as a colorless oil.
1H-NMR (CDCl3, TMS) δ (ppm) : 3.11 (3 H, s), 3.73 (3 H, s), 4.13 (2 H, br s) .
Step 2: Preparation of N'- (3- { [5-bromo-2- (3-chloro-pyridin -2-yl) -2E-pyrazole-3-carbonyl] -amino} -6-chloro-4-methyl- pyridine-2-carbonyl) -N-methyl-hydrazinecarboxylic acid methyl ester (8)
2- [5-Bromo-2- (3-chloro-pyridin-2-yl) -2H-pyrazol-3-yl] -6- chloro-8-methyl-pyrido [3, 2-d] [1, 3] oxazin-4-one (140 mg)
(example 7, step 4) was -dissolved in DMF (10 inL) and N- methyl-hydrazinecarboxylic acid methyl ester (161 mg) was added. The solution was stirred for 3 hours at 80°C, then
12 hours at room temperature and again for 3.5 hours at 800C. The reaction mixture was quenched was diluted with MTB-ether and washed 4x with water, washed with brine, dried over MgSO4 and concentrated in vacuum. The residue was purified by column chromatography (hexane/ethyl acetate = 2:1, then 1.5:1, Rf = 0.15 in hexane/ethyl acetate = 2:1) to afford 112 mg of compound 8 of the present invention of the formula
Figure imgf000442_0001
as a white solid.
1H-NMR (CDCl3, TMS) δ (ppm) : 2.26 (3H, s), 3.28 (3H, s) , 3.77 (3H, br s), 7.11 (IH, s) , 7.35 (IH, s) , 7.39 (IH, dd,
J = S Hz, 5 Hz), 7.86 (IH, dd, J = S Hz, 2 Hz), 8.47 (IH, dd, J = 5 Hz, 2 Hz), 9.58 (IH, s) , 11.06 (IH, s) . Example 9: Preparation of N'- (3- { [5-bromo-2- (3-chloro- pyridin- 2-yl) -2E-pyrazole-3-carbonyl] -amino} -6-chloro-4- methyl- pyridine-2-carbonyl) -N,N'-dimethyl- hydrazinecarboxylic acid methyl ester (9)
Step 1: Preparation of 5-bromo-2- (3-chloro-pyridin-2-yl) - 2H- pyrazole-3-carboxylic acid [ 6-chloro-2- (N,JJ'-dimethyl- hydrazinocarbonyl) -4-methyl-pyridin-3-yl] -amide 1, 2-Dimethylhydrazine dihydrochloride (176 mg) and potassium carbonate (366 mg) were suspended in THF (8 mL) and 10 drops of water , 2- [5-bromo-2- (3-chloro- pyridin-2- yl) -2if-pyrazol- 3-yl] -6-chloro-8-methyl-pyrido [3, 2-d] [1, 3] oxazin-4-one ~ (example 7, step 4) (300 mg) was added and the reaction mixture was stirred for 20 h at room temperature ." Water and ethyl acetate were added, the layers were separated and the aqueous layer was 2x extracted with ethyl acetate. The combined organic layer was washed with brine, dried over magnesium sulfate and concentrated in vacuum. The residue was purified by column chromatography (silica 60, chloroform/ethyl acetate = 1:1, Rf = 0.13) to afford 300 mg of the title compound of the formula
Figure imgf000444_0001
as a white solifi.
1H-NMR ('CDCl3, TMS) δ (ppm) : 2.10 (1.5H, s), 2.13 (1.5H, s), 2.43 (1.5H, s), 2.66' (1.5H, s) , 3.00 (1.5H, s), 3.23 (1.5H, s), 3.97 (0.5H, br s), 5.52 (0.5H, br s), 7.04 (0.5H, s), 7.11 (0.5H, s), 7.26 (0.5H, s) , 7.32 (0.5H, s), 7.35-7.40 (1.0H, m) , 7.82-7.87 (1.0H, m) , 8.43-8.47 (1.0H, m) , 10.07 (0.5H, s) , 10.16 (0.5H, s) .
Step 2: Preparation of N'- (3- { [5-bromo-2- (3-chloro-pyridin-
2^ yl) -2ff-pyrazole-3-carbonyl] -amino} -6-chloro-4-methyl- pyridine-2-carbonyl) -N/.iV'-dimethyl-hydrazinecarboxylic acid methyl ester
5-Bromo-2- (3-chloro-pyridin-2-yl) -2F-pyrazole-3-carboxylic acid [6-chloro-2- (iV,N'-dimethyl-hydrazinocarbonyl) -4- methyl-pyridin-3-yl] -amide (250 mg) was dissolved in pyridine (3 πiL) , methyl chloroformate (150 μL) was added and the reaction mixture was stirred at room temperature. After 30 min, 1 h and 1.5 h, methyl chloroformate (each 75 μL) was added. After 1 h stirring at room temperature, the reaction mixture was quenched with water and 3x co- evaporated with toluene. The residue was dissolved in water and ethyl acetate, the layers were separated and the aqueous layer was extracted 2x with ethyl acetate. The combined organic layer was washed with brine, dried over magnesium sulfate and concentrated in vacuum. The residue was purified by column chromatography (silica 60, hexane/ethyl acetate = 1:1, Rf = 0.20) to afford 223 mg of compound (9) of the present invention of the formula
Figure imgf000445_0001
as a white solid. 1H-NMR (DMSO-D6) δ (ppm) : 2.17 (1.5H, s), 2.24 (1.5H, s), 2.77 (1.5H, s), 2.84-2.85 (1.5H, m) , 2.91-2.93 (1.5H, m) , 3.09 (1.5H, s), 3.49 (2.5H, s), 3.69 (0.5H, s), 7.35-7.39 (1.0H, m) , 7.61-7.68 (2.0H, m) , 8.19-8.22 (1.0H, m) , 8.49- 8.52 (1.0H, m) , 10.51-10.65 (1.0H, br m) .
Example 10: Preparation of N'- (3- { [5-bromo-2- (3-chloro- pyridin -2-yl) -2H-pyrazole-3-carbonyl] -amino} -6-chloro-4- methyl- pyridine-2-carbonyl) -N-ethyl-hydrazinecarboxylic acid methyl ester (10) and N'- (3-{ [5-bromo-2- (3-chloro-pyridin-2-yl) -2fl-pyrazole-3- carbonyl] -amino} -6-chloro-4-methyl-pyridine-2-carbonyl) -N'- ethyl-hydrazine carboxylic acid methyl ester (11)
Step 1: Preparation of 5-bromo-2- (3-chloro-pyridin-2-yl) - 2H- pyrazole-3-carboxylic acid [ 6-chloro-2- (N'-ethyl- hydrazine carbonyl) -4-methyl-pyridin-3-yl] -amide (10-a and 5-bromo-2- (3-chloro-pyridin-2-yl) -2H-pyrazole-3-carboxylic acid [ 6-chloro-2- (N-ethyl- hydrazinocarbonyl) -4-methyl- pyridin-3-yl] -amide (11-a) 2- [5-Bromo-2- (3-chloro-pyridin-2-yl) -2H-pyrazol-3-yl] -6- chloro-8-methyl-pyrido [3, 2-d] [1, 3] oxazin-4-one (example 7, step 4) (600 mg) was suspended in THF (16 mL) , and ethyl hydrazine oxalate (398 mg) and potassium carbonate (732 mg) were added and the reaction mixture was stirred for 19 h at room temperature. Water and ethyl acetate were added and the layers were separated. The aqueous layer was Ix extracted with ethyl acetate, the combined organic layer were washed with brine, dried over magnesium sulfate and concentrated in vacuum. The residue was purified by column chromatography (silica 60, chloroform/ethyl acetate 5:1, then 3:1, then 1:1, Rf (10-a) = 0.45, Rf (11-a) = 0.15 in chloroform/ethyl acetate = 1:1) to afford 380 mg of the title compound (10-a) of the formula
Figure imgf000447_0001
as a white solid and 228 mg of the title compound (11-a) of the formula
Figure imgf000447_0002
as a white solid.
(10-a): 1H-NMR (CDCl3, TMS) δ (ppm) : 1.18 (3H, t, J = 7 Hz), 2.25 (3H, s), 2.99 (2H, q, J = 1 Hz), 4.69 (IH, br s), 7.13 (IH, s), 7.29 (IH, s), 7.39 (IH, dd, J= 8 Hz, 5 Hz), 7.86 (IH, dd, J= Q Hz, 2 Hz), 8.48 (IH, dd, J= 5 Hz, 2 Hz), 9.18 (IH, br s), 11.45 (IH, s).
(11-a): 1H-NMR (CDCl3, TMS) δ (ppm): 1.09-1.19 (3.0H, m) , 2.08 (1.7H, s), 2.11 (1.3H, s) , 3.28 (0.8H, q, J = 1 Hz), 3.63 (1.2H, q, J = 7 Hz), 4.16 (1.2H, s), 4.45 (0.8H, s), 7.01 (0.6H, s), 7.09 (0.4H, s) , 7.31-7.33 (1.0H, m) , 7.35- 7.41 (1.0H, m) , 7.83-7.88 (1.0H, m) , 8.43-8.48 (1.0H, m) , 10.24 (0.4H, s), 10.56 (0.6H, s).
Step 2: Preparation of N'- (3-{ [5-bromo-2- (3-chloro-pyridin -2-yl) -2ff-pyrazole-3-carbonyl] -amino} -6-chloro-4-methyl- pyridine-2-carbonyl ) -N-ethyl-hydrazinecarboxylic acid methyl ester (10)
5-Bromo-2- (3-chloro-pyridin-2-yl) -2H-pyrazole-3-carboxylic acid [6-chloro-2- (iV'-ethyl- hydrazinocarbonyl) -4-methyl- pyridin-3-yl] -amide (10-a) (320 mg) was dissolved in pyridine (4 mL) , methyl chloroformate (190 μL) was added and the reaction mixture was stirred at room temperature. After 30 min, 1 h and 1.5 h, methyl chloroformate (each 95 μL) was added. After 1 h stirring at room temperature, the reaction mixture was quenched with water and 3x co- evaporated with toluene. The residue was dissolved in water and ethyl acetate, the layers were separated and the aqueous layer was extracted 2x with ethyl acetate. The combined organic layer was washed with brine, dried over magnesium sulfate and concentrated in vacuum. The residue was purified by column chromatography (silica 60, hexane/ethyl acetate = 2:1, Rf = 0.10) to afford 308 mg of the title compound (10) of the present invention of the formula
Figure imgf000448_0001
as a white solid . 1H-NMR (CDCl3, TMS) δ (ppm) : 1.22 (3H, t, J = 1 Hz) , 2.26 (3H, s), 3.69 (2H, q, J = 1 Hz), 3.76 (3H, s), 7.10 (IH, s), 7.35 (IH, s), 7.39 (IH, dd, J = 8 Hz, 5 Hz) , 7.86 (IH, dd, J = 8 Hz, 2 Hz) , 8.48 (IH, dd, J = 5 Hz, 2 Hz) , 9.52 (IH, s) , 11.09 (IH, s) .
Step 3: N'- (3- { [5-bromo-2- (3-chloro-pyridin-2-yl) -2H- pyrazole-3-carbonyl] -amino} -6- chloro-4- methyl -pyridine- 2- carbonyl) -Af'-ethyl-hydrazine carboxylic acid methyl ester (11)
5-Bromo-2- (3-chloro-pyridin-2-yl) -2E-pyrazole-3-carboxylic acid [6-chloro-2- (iV-ethyl- hydrazinocarbonyl) -4-methyl- pyridin-3-yl] -amide (11-a) (177 mg) was dissolved in pyridine (2 mL) , methyl chloroformate (100 μL) was added and the reaction mixture was stirred at room temperature. After 30 min, 1 h and 1.5 h, methyl chloroformate (each 50 μL) was added. After 14 h stirring at room temperature, the reaction mixture was quenched with water and 3x co- evaporated with toluene. The residue was dissolved in water and ethyl acetate, the layers were separated and the aqueous layer was extracted 2x with ethyl acetate. The combined organic layer was washed with brine, dried over magnesium sulfate and concentrated in vacuum. The residue was purified by column chromatography (silica 60, chloroform/ethyl acetate = 3:1, Rf = 0.10) to afford 135 mg of the title compound (11) of the present invention of the formula
Figure imgf000450_0001
as a white solid. 1H-NMR (CDCl3, TMS) δ (ppm) : 1.14-1.27 (3H, m) , 2.17 (3H, s), 3.62-3.80 (5H, m) , 7.12 (2H, s), 7.20-7.22 (IH, m) , 7.39 (IH, dd, J = 8 Hz, 5 Hz), 7.87 (IH, dd, J = 8 Hz), 8.46 (IH, d, J = 5 Hz), 9.53 (IH, br s) .
Example 11; Preparation of N'- (3- { [5-bromo-2- (3-chloro- pyridin-2-yl) -2H-pyrazole-3-carbonyl] -amino} -6-chloro-4- methyl- pyridine-2-carbonyl) -N-isopropyl-hydrazine carboxylic acid methyl ester (12) and
N'- (3-{ [5-bromo-2- (3-chloro-pyridin-2-yl) -2E-pyrazole-3- carbonyl] -amino} -6-chloro-4-methyl-pyridine-2-carbonyl) -N'- isopropyl-hydrazinecarboxylic acid methyl ester (13)
Step 1: Preparation of 5-bromo-2- (3-chloro-pyridin-2-yl) - 2H- pyrazole-3-carboxylic acid [ 6-chloro-2- (JJf-isopropyl- hydrazinocarbonyl) -4-methyl-pyridin-3-yl] -amide (12-a) and 5-bromo-2- (3-chloro-pyridin-2-yl) -2H-pyrazole-3-carboxylic acid [6-chloro-2- (N-isopropyl -hydrazinocarbonyl) -4-methyl- pyridin-3-yl] -amide (13-a)
2- [5-Bromo-2- (3-chloro-pyridin-2-yl) -2H-pyrazol-3-yl] -6- chloro-8-methyl-pyrido [3, 2-d] [1, 3] oxazin-4-one (example 7, step 4) (600 mg) was suspended in THF (16 mL) , isopropyl hydrazine (294 mg) was added and the reaction mixture was stirred for 19 h at room temperature. Water and ethyl acetate were added and the layers were separated. The aqueous layer was Ix extracted with ethyl acetate, the combined organic layers were washed with brine, dried over magnesium sulfate and concentrated in vacuum. The residue was purified by column chromatography (silica 60, hexane/ethyl acetate 2:1, then 1:1, Rf (12-a) = 0.35, Rf
(13-a) = 0.15 in hexane/ethyl acetate = 1:1) to afford 478 mg of the title compound (12-a) of the formula
Figure imgf000451_0001
as a white solid and 121 mg of the title compound (13-a) of the formula
Figure imgf000452_0001
as a white solid.
(12-a) 1H-NMR (CDCl3, TMS) δ (ppm) : 1.14 (6H, d, J = 6 Hz), 2.25 (3H, s), 3.17-3.23 (IH, m) , 4.63 (IH,
Figure imgf000452_0002
7.12 (IH, s), 7.29 (IH, s), 7.37-7.41 (IH, m) , 7.84-7.87 (IH, m) , 8.46- 8.48 (IH, m), 9.15 (IH, s), 11.46 (IH/ s). (13-a) 1H-NMR (CDCl3, TMS) δ (ppm): 1.09 (3.0H, d, J = 1 Hz), 1.12 (3.0H, d, J = 7 Hz), 2.08 (1.5H, s), 2.11 (1.5H, s), 3.75-3.80 (0.5H, m) , 3.80-4.16 (2.0H, br m) , 4.69-4.75 (0.5H, m) , 7.02 (0.5H, s), 7.09 (0.5H, s) , 7.29 (0.5H, s), 7.31 (0.5H, s), 7.34-7.39 (1.0H, in), 7.82-7.86 (1.0H, m) , 8.41-8.46 (1.0H, m) , 10.12 (0.5H, s) , 10.42 (0.5H, s).
Step 2: Preparation of N'- (3- { [5-bromo-2- (3-chloro-pyridin -2-yl) -2E-pyrazole-3-carbonyl] -amino} -6-chloro-4-methyl- pyridine-2-carbonyl) -N-isopropyl-hydrazine carboxylic acid methyl ester (12)
5-Bromo-2- (3-chloro-pyridin-2-yl) -2E-pyrazole-3-carboxylic acid [6-chloro- 2- (N'-isopropyl-hydrazinocarbonyl) -4- methyl- pyridin-3-yl] -amide (12-a) (378 mg) was dissolved in pyridine (5 mL) , methyl chloroformate (220 μL) was added and the reaction mixture was stirred at room temperature. After 30 min, 1 h and 1.5 h, methyl chloroformate (each 110 μL) was added. After 18 h stirring at room temperature, the reaction mixture was quenched with water and 3x co- evaporated with toluene. The residue was dissolved in water and ethyl acetate, the layers were separated and the aqueous layer was extracted 2x with ethyl acetate. The combined organic layer was washed with brine, dried over magnesium sulfate and concentrated in vacuum. The residue was purified by column chromatography (silica 60, chloroform/ethyl acetate = 10:1, Rf = 0.13) to afford 382 mg of the title compound (12) of the present invention of the formula
Figure imgf000453_0001
as a white solid. 1H-NMR (CDCl3, TMS) δ (ppm) : 1.20 (6H, d, J = 7 Hz), 2.26 (3H, s), 3.75 (3H, s) , 4.54-4.60 (IH, m) , 7.09 (IH, s), 7.36 (IH, s), 7.39 (IH, dd, J = 8 Hz, 5 Hz), 7.85 (IH, dd, J = 8 Hz, 2 Hz), 8.48 (IH, dd, J = 5 Hz, 2 Hz), 9.28 (IH, s) , 11.12 (IH, s) .
Step 3: N'- (3- { [5-bromo-2- (3-chloro-pyridin-2-yl) -2H- pyrazole-3-carbonyl] -amino}-6- chloro-4- methyl -pyridine- 2- carbonyl) -N'-isopropyl-hydrazinecarboxylic acid methyl ester (13)
5-Bromo-2- (3-chloro-pyridin-2-yl) -2H-pyrazole-3-carboxylic acid [6-chloro-2- (i\7-isopropyl -hydrazinocarbonyl) -4-methyl- pyridin-3-yl] -amide (13-a) (121 mg) was dissolved in pyridine (2 mL) , methyl chloroformate (70 μL) was added and the reaction mixture was stirred at 500C. After Ih, methyl chloroformate (each 40 μL) was added 8x in a time interval of 30 min at 500C. After 10 h stirring at room temperature, the reaction mixture was quenched with water and 3x co- evaporated with toluene. The residue was dissolved in water and ethyl acetate, the layers were separated and the aqueous layer was extracted 2x with ethyl acetate. The combined organic layer was washed with brine, dried over magnesium sulfate and concentrated in vacuum. The residue was purified by column chromatography (silica 60, chloroform/ethyl acetate = 3:1, Rf = 0.15) to afford 67 mg of the title compound (13) of the present invention of the formula
Figure imgf000454_0001
as a white solid. 1H-NMR (CDCl3, TMS) δ (ppm) : 1.00-1.30 (6H, m) , 2.14 (3H, s) f 3.57-3.81 (3H, br m) , 4.62-4.79 (IH, m) , 6.96-7.18 (3H, m) , 7.39 (IH, dd, J = 8 Hz, 5 Hz) , 7.86 (IH, dd, J = 8 Hz), 8.45 (IH, d, J = 5 Hz), 9.66-9.86 (IH, m) .
Example 12: Preparation of N' ' - (3- { [5-bromo-2- (3-chloro- pyridin-2-yl) -2H-pyrazole-3-carbonyl] -amino} -4, 6-dichloro- pyridine-2-carbonyl) -hydrazinecarboxylic acid methyl ester (14)
Step 1; Preparation of 2-chloro-pyridin-3-ylamine 3-Aminopyridine (25.0 g) was dissolved in concentrated hydrochloric acid (250 mL, 37%) at 30 to 35°C and cooled in an ice bath after complete dissolution of the starting material. Hydrogen peroxide (28.5 mL, 30% aqueous solution) was added slowly with a dropping funnel to the solution in a rate that the temperature was kept below 100C over a period of 30 min . The orange solution was slowly warmed up to room temperature over a time period of 2 h and stirred at room temperature for another 2 h. The solution was cooled in an ice bath and 160 mL of an aqueous sodium hydroxide solution (50%) were added slowly. The acidic aqueous solution was washed with 30 mL toluene and the organic washing was re-extracted Ix with 5 N aqueous hydrochloric acid. Aqueous sodium hydroxide solution (50%) was added to the combined acidic aqueous solution and the pH was adjusted to ~8-10. The aqueous solution was 3x extracted with 200 mL toluene, the combined organic layer was washed with brine, dried over magnesium sulfate and concentrated in vacuum. The residue was purified by column chromatography (silica 60, chloroform/ethyl acetate 20:1, Rf = 0.25) to afford 17.6 g of the title compound of the formula
Figure imgf000456_0001
as an orange solid.
1H-NMR (CDCl3, TMS) δ (ppm) : 4.12 (2H, br s), 7.04-7.05 (2H, m) , 7.78-7.81 (IH, m) .
Step 2: Preparation of 3-aiτtino-pyridine-2-carbonitrile
2-Chloro-pyridin-3-ylamine (2.0 g) was dissolved in DMF (24 mL) and zinc cyanide (1.83 g) was added to the solution. The solution was degassed in vacuum 5x, tetrakis (triphenylphosphine) palladium(O) (901 mg) was added and the reaction mixture was stirred at 900C for 7 h. After the reaction mixture was cooled to room temperature, the solid was removed by filtration and the filter cake was washed with ethyl acetate. Water was added to the filtrate, the layers were separated and the aqueous layer was 2x extracted with ethyl acetate. The combined organic layer was washed 3x with water, washed with brine, dried over magnesium sulfate and concentrated in vacuum. The residue was purified by column chromatography (silica 60, chloroform/ethyl acetate 3:1, Rf = 0.25) to afford 755 mg of the title compound of the formula
Figure imgf000457_0001
as a white solid.
1H-NMR (CDCl3, TMS) δ (ppm) : 4.43 (2H, br s) , 7.10 (IH, dd, J = 9 Hz, 1 Hz), 7.25-7.29 (IH, m) , 8.07 (IH, dd, J = 4 Hz,
1 Hz) .
Step 3: Preparation of 3-amino-4 , 6-dichloro-pyridine-2- carbonitrile 3-Amino-pyridine-2-carbonitrile (100 mg) was dissolved in DMF (2 mL) and N-chorosuccinimide (246 mg) was added. The solution was stirred for 20 h at room temperature before water was added. The mixture was 2x extracted with ethyl acetate, the combined organic layer was washed 3x with water, washed with brine, dried over magnesium sulfate and concentrated in vacuum. The residue was purified by column chromatography (silica 60, hexane/ethyl acetate = 3:1, Rf = 0.30) to afford 121 mg of the title compound of the formula
Figure imgf000458_0001
as an orange solid.
1H-NMR (CDCl3, TMS) δ (ppm) : 4.92 (2H, br s), 7.44 (IH, s).
Step 4: Preparation of 3-amino-4 , 6-dichloro-pyridine-2- carboxylic acid
3-Amino-4 , β-dichloro-pyridine-2-carbonitrile (121 mg) was dissolved in concentrated sulfuric acid (1 mL) and stirred for 1 h at 1000C. The reaction mixture was cooled to room temperature and water (1 mL) was slowly added. The reaction mixture was warmed again to 1000C and stirred at this temperature for 2 h. Water was added after cooling to room temperature, the pH was adjusted to -10 by addition of solid sodium bicarbonate and the aqueous solution was washed 2x with MTB-ether. The aqueous layer was then adjusted to pH ~2 by addition of 2 M hydrochloric acid and extracted 3x with ethyl acetate. The combined organic layer was washed with brine, dried over magnesium sulfate and concentrated in vacuum to afford 99 mg of the title compound of the formula
Figure imgf000458_0002
as a yellow solid.
1H-NMR (CDCl3, TMS) δ (ppm) : 6.37 (2H, br s) , 7.47 (IH, s), 10.50 (IH, br s) .
Step 5: Preparation of N'- (3- { [5-bromo-2- (3-chloro-pyridin -2-yl) -2#-pyrazole-3-carbonyl] -amino} -4 , 6-dichloro- pyridine-2-carbonyl) -hydrazinecarboxylic acid methyl ester 5-Bromo-2- (3-chloro-pyridin-2-yl) -2H-pyrazole-3-carboxylic acid (example 1, step 5) (142 mg) was suspended in acetonitrile (1 πiL) and pyridine (65 μL) and methanesulfonyl chloride (50 μL) were added. The reaction mixture was stirred for 30 min at room temperature, 3- amino-4 , 6-dichloro-pyridine-2-carboxylic acid (99 mg) in acetonitrile (1 mL) and pyridine (130 μL) were added and the reaction mixture was stirred 1 h at room temperature. Methanesulfonyl chloride (65 μL) was added and the reaction mixture was stirred for 20 h at room temperature. The reaction mixture was concentrated in vacuum, the residue was suspended in DMF (5 mL) , carbazaic acid methyl ester (216 mg) was added and the reaction mixture was stirred for 20 h at room temperature. Water was added and the mixture was 2x extracted with MTB-ether. The combined organic layer was washed 3x with water, washed with brine, dried over magnesium sulfate and concentrated in vacuum. The residue was purified by column chromatography (silica 60, hexane/ethyl acetate = 2:1, Rf = 0.15) to afford 37 mg of the compound 14 of the present invention of the formula
Figure imgf000460_0001
as a white solid. 1H-NMR (CDCl3, TMS) δ (ppm) : 3.82 (3H, s) , 6.66 (IH, br s) ,
7.08 (IH, s), 7.39 (IH, dd, J = 8 Hz, ' 5 Hz) , 7.57 (IH, s) , 7.86 (IH, dd, J = 8 Hz, 2 Hz), 8.47 (IH, dd, J = 5 Hz, 2 Hz), 9.40 (IH, s), 10.71 (IH, s) .
Example 13: Preparation of N'- (4-bromo-3- { [5-bromo-2- (3- chloro -pyridin-2-yl) -2ff-pyrazole-3-carbonyl] -amino} -6- chloro- pyridine-2-carbonyl) -hydrazine carboxylic acid methyl ester (15)
Step 1: Preparation of 3-amino-6-chloro-2-iodopyridine
5-Amino-2-chloropyridine (3.0 g) was dissolved in DMF (40 mL) , N-iodosuccinimide (5.25 g) was added and the reaction mixture was stirred at room temperature for 3 hours. Water and MTB-ether were added to the reaction mixture, the layers were separated and the organic layer was washed 3x with water, washed with brine, dried over MgSO4 and concentrated in vacuum. The residue was purified by column chromatography (silica 60, hexane/ethyl acetate = 3:1, Rf = 0.30) to afford 4.80 g of the title compound of the formula
Figure imgf000461_0001
as an orange solid. 1H-NMR (CDCl3, TMS) δ (ppm) : 4.13 (2H, br s) , 6.89 (IH, d, J = 8 Hz), 7.05 (IH, d, J = 8 Hz).
Step 2: Preparation of 3-amino-6-chlorb-2- (2- furanyl) pyridine 3-Amino-6-chloro-2-iodopyridine (1.78 g) , 2-furanboronic acid (1.17 g) , and sodium carbonate (1.11 g) were suspended in a solvent mixture consistent of toluene (23 mL) , THF (23 mL) and water (7 mL) . The mixture was degassed using subsequent evaporation and flushing with nitrogen (5x) and tetrakis (triphenylphosphine) palladium(O) (808 mg) was added. The reaction mixture was stirred at 900C for 7 hours and 14 hours at room temperature. After addition of 2-furanboronic acid (783 mg) , the mixture was stirred again for 4 hours at 900C, then another portion of 2-furanboronic acid (390 mg) was added and the reaction mixture was stirred for 5.5 hours at 900C. After 15 hours stirring at room temperature, the reaction mixture was quenched with water and extracted 2x with ethyl acetate. The combined organic layer was washed with brine, dried over MgSC>4 and concentrated in vacuum. The residue was purified by column chromatography (silica 60, hexane/ethyl acetate = 3:1, Rf = 0.25) to afford 1.26 mg of the title compound of the formula
Figure imgf000462_0001
as beige solid. The compound contained ~10% 3-amino-6- chloro-2-iodopyridine and was used without further purification in the next step.
1H-NMR (CDCl3, TMS) δ (ppm) : 4.65 (2H, ' br s) , 6.56 (IH, dd, J = 4 Hz, 2 Hz), 6.99 (2H, s), 7.08 (IH, d, J = 4 Hz), 7.54 (IH, d, J = 2 Hz) .
Step 3: Preparation of 3-amino-6-chloro-pyridine-2- carboxylic acid
3-Amino-6-chloro-2- (2-furanyl) pyridine (1.06 g) was dissolved in acetone (25 mL) and cooled in an ice bath to 0°C. A solution prepared of potassium permanganate (2.57 g) in water (40 mL) was added drop wise to this solution. After complete addition, the reaction mixture was allowed to warm to room temperature and stirred for hours. The mixture was cooled again to 0°C and a second portion of potassium permanganate (858 mg) in water (15 mL) was added and the cool bath removed. After stirring for 2 hours, the reaction mixture was filtered through a pad of celite, the filter cake was washed carefully with water, methanol and ethyl acetate and concentrated to approx. 20 mL on a rotary evaporator. 2N Sodium hydroxide solution was added to adjust the pH-value to -12 and the aqueous layer was washed 2x with MTB-ether. The aqueous layer was adjusted to pH~2 by addition of 6N hydrochloric acid and extracted 3x with MTB-ether. The combined organic layer was washed with brine, dried over MgSO4 and concentrated in vacuum to afford 636 mg of the title compound of the formula
CrjcNxmCO* 2H as a brown solid. The compound still contained -30% of an unknown impurity and was used in the next step without further purification.
1H-NMR (DMSO-D6) δ (ppm) : 7.28 (IH, d, J = 9 Hz), 7.34 (IH, d, J = 9 Hz) .
Step 4: Preperation of 3-amino-6-chloro-pyridine-2- carboxylic acid methyl ester
3-Amino-6-chloro-pyridine-2-carboxylic acid (636 mg) was suspended in methanol (8 mL) and toluene (22 mL) was added. A solution of (trimethylsilyl) diazomethane (2.0 M in hexane,
2.4 mL) was added slowly to the reaction mixture. After 1 hour stirring at room temperature, another portion of
(trimethylsilyl) diazomethane (550 μl) was added and the mixture was stirred for additional 45 minutes. The reaction mixture was quenched with water and extracted 3x with ethyl acetate. The combined organic layer was washed with 2N hydrochloric acid, saturated bicarbonate solution and brine, dried over MgSO4 and concentrated in vacuum. The residue was purified by column chromatography (silica gel 60, choroform/ethyl acetate = 50:1, Rf = 0.30) to afford 365 mg of the title compound of the formula
Figure imgf000464_0001
as a yellow solid. The compound still contained -30% of an unknown impurity and was used in the next step without further purification.
1H-NMR (CDCl3, TMS) δ (ppm) : 3.96 (3H, s) , 5.82 (2H, br s), 7.05 (IH, d, J = 9 Hz), 7.23 (IH, d, J = 9 Hz).
Step 5: Preparation of 3-amino-4-bromo-6-chloro-pyridine-2- carboxylic acid methyl ester
3-Amino-6-chloro-pyridine-2-carboxylic acid methyl ester (365 mg) was dissolved in DMF (10 mL) and N-bomosuccinimide (418 mg) was added. The solution was stirred at 50°C for 5 hours and diluted with MTB-ether. The organic layer was washed 4x with water, washed with brine, dried over MgSO4 and concentrated in vacuum. The residue was purified by column chromatography (silica 60, hexane/ethyl acetate = 5:1, Rf = 0.25) to afford 169 mg of 3-amino-4-bromo-6- chloro-2-picolinic acid methyl ester
Figure imgf000465_0001
as an orange solid.
1H-NMR (CDCl3, TMS) δ (ppm) : 3.97 (3H, s) , 6.39 (2H, br s) , 7.58 (IH, s) .
Step 6: Preparation of 3-aittino-4-bromo-6-chloro-pyridine - 2-carboxylic acid 3-Amino-4-bromo-6-chloro-pyridine-2-carboxylic acid methyl ester (169 mg) was suspended in methanol (3 mL) and 2N sodium hydroxide solution (2 mL) . The suspension was stirred at 500C for 3 hours. The precipitate was filtered off and washed carefully with diethyl ether. The precipitate was dissolved in a mixture of 2N hydrochloric acid and ethyl acetate and the layers were separated. The aqueous layer was 2x extracted with ethyl acetate, washed with brine, dried over MgSO4 and concentrated in vacuum to afford 138 mg of the title compound of the formula
Figure imgf000465_0002
as a white solid.
1H-NMR (CDCl3, TMS) δ (ppm) : 6.46 (2H, br s) , 7.63 (IH, s), 10 . 59 ( IH , br s ) .
Step 7: Preparation of 8-bromo-2- [5-bromo-2- (3-chloro- pyridin -2-yl) -2H-pyrazol-3-yl] -6-chloro-pyrido [3,2- d] [1, 3] oxazin-4-one
A mixture of 5-bromo-2- (3-chloro-pyridin-2-yl) -2H-pyrazole -3-carboxylic acid (example 1, step 5) (183 mg) and thionyl chloride (130 μl) was stirred under reflux for 2 hours. Excess thionyl chloride was co-evaporated with dry toluene on a evaporator, the residue re-dissolved in dry acetonitrile (3 mL) and 3-amino-4-bromo-6-chloro-pyridine- 2-carboxylic acid (138 mg) was added. The solution was stirred for 15 minutes at room temperature and triethylamine (85 μL) was added and stirred for 30 minutes, before a second portion of triethylamine (170 μL) was added. After the mixture was stirred for further 30 minutes at room temperature, methanesulfonyl chloride (55 μL) was added. After stirring for 21 hours at room temperature, the reaction mixture was quenched by slow addition of water. The precipitate was filtered off, washed with water/acetonitrile (1 : 2), acetonitrile and diethyl ether and dried in vacuum to afford 141 mg of the title compound of the formula
Figure imgf000467_0001
as a yellow solid.
1H-NMR (CDCl3, TMS) δ (ppm) : 7.33 (IH, s) , 7.4! (IH, dd, J = 8 Hz, 5 Hz) , 7.88 (IH, s) , 7.98 (IH, dd, J = Hz, 2 Hz) , 8.55 (IH, dd, J = 5 Hz, 2 Hz) .
Step 8: Preparation of N'- (4-bromo-3- { [5-bromo-2- (3-chloro- pyridin-2-yl) -2H-pyrazole-3-carbonyl] -amino} -6-chloro- pyridine-2-carbonyl) -hydrazine carboxylic acid methyl ester (15)
8-Bromo-2- [5-bromo-2- (3-chloro-pyridin-2-yl) -2H-pyrazol-3 - yl] -6-chloro-pyrido [3, 2-d] [1, 3] oxazin-4-one (141 mg) was dissolved in DMF (8 mL) and carbazaic acid methyl ester (243 mg) was added. The solution was stirred for 14 hours at room temperature. The reaction mixture was diluted with MTB-ether and the organic layer was washed 4x with water, brine, dried over MgSO4 and concentrated in vacuum. The residue was purified by column chromatography (silica 60, chloroform/ethyl acetate = 3 : 1, Rf = 0.20) to afford 120 mg of compound 15 of the present invention of the formula
Figure imgf000468_0001
as a white solid.
1H-NMR (DMSO-D6) δ (ppm) : 3.46-3.62 (3H, br m) , 7.45 (IH, s), 7.61 (IH, dd, J = 8 Hz, 5 Hz), 8.16 (IH, dd, J = 8 Hz, 2 Hz), 8.28 (IH, s) , 8.50 (IH, dd, J = 5 Hz, 2 Hz), 9.31 (IH, br s), 10.45 (IH, s) , 10.72 (IH, s) .
Example 14: Preparation of N'~ (4 , 6-dibromo-3- { [5-bromo-2- (3-chloro-pyridin-2-yl) -2ff-pyrazole-3-carbonyl] -amino} - pyridine-2-carbonyl ) -N'-ethyl-hydrazinecarboxylic acid methyl ester (16)
Step 1: Preparation of N'-ethylidene-hydrazinecarboxylic acid methyl ester Carbazaic acid methyl ester (10 g) was suspended in toluene
(60 mL) and warmed up to 5O0C for 10 min. The flask was equipped with a dropping funnel, filled with a solution of acetaldehyde (5.86 g) in toluene (20 mL) and the solution was slowly dropped to the suspension within 10 min. The mixture was stirred for 1 h at 50 °C, and then cooled to room temperature. The product started crystallizing and cooling in an ice bath completed the crystallizing process. The white crystals were filtered off, washed with small amounts of cold toluene and dried in vacuum to give 12.07 g of the title compound of the formula
Figure imgf000469_0001
as white crystals (mainly one diastereomer) .
1H-NMR (CDCl3, TMS) δ (ppm) : 1.99 (3H, d, J = 5 Hz), 3.82 (3H, br s) , 7.24 (IH, q, J = 5 Hz) , 8.O6-8.56 (IH, br m) .
Step 2: Preparation of N'-ethyl-hydrazinecarboxylic acid methyl ester
N'-Ethylidene-hydrazinecarboxylic acid methyl ester (5.0 g) was dissolved in of dry THF (50 mL) and stirred at 5O0C. Sodium borohydride (1.95 g) (gas evolution) and dry methanol (4.2 mL) were added. The suspension turned into a solution within 5 to 10 min and the gas evolution ceased within 30 min. The solution was stirred for 3 h at 50 "C, before 50 mL dry methanol was added and the solution was stirred under reflux for 2 h. The solvent was removed on an evaporator and the residue was treated with 20 mL of chloroform and stirred for 10 min at 50 °C, before it was filtered over a pad of celite and was washed 3x with 30 mL of chloroform. The filtrate was concentrated in vacuum and the residue was purified by column chromatography (silica 60, chloroform/ethyl acetate = 3:1; Rf = 0.20) to afford 3.70 g of the title compound of the formula
^-N-NH
H CO2Me
as colorless oil. 1H-NMR (DMSO-D6) δ (ppm) : 0.93 (3H, t, J = 1 Hz) , 2.66-2.73 (2H, m) , 3.54 (3H, s) , 4.39-4.42 (IH, m) , 8.45 (IH, br s) .
Step 3: Preparation of 3-amino-4 , 6-dibromo-pyridine-2-carbo nitrile 2-Chloro-pyridin-3-ylamine (100 mg) was dissolved in DMF (2 mL) and N-bromosuccinimide (329 mg) was added. The solution was stirred for 26 h at room temperature before water was added. The mixture was 2x extracted with ethyl acetate, the combined organic layer was washed 3x with water, washed with brine, dried over magnesium sulfate and concentrated in vacuum. The residue was purified by column chromatography (silica 60, hexane/ethyl acetate = 3:1, Rf = 0.30) to afford 158 mg of the title compound of the formula
Figure imgf000470_0001
as a beige solid.
1H-NMR (CDCl3, TMS) δ (ppm): 4.93 (2H, s) , 7.72 (IH, s). Step 4: Preparation of 3-amino-4 , 6-dibromo-pyridine-2- carboxylic acid
3-amino-4 , 6-dibromo-pyridine-2-carbonitrile (158 mg) was dissolved in concentrated sulfuric acid (1.5 mL) and stirred for 1 h at 1000C. The reaction mixture was cooled to room temperature and water (1.5 mL) was slowly added. The reaction mixture was warmed again to 1000C and stirred at this temperature for 2 h. Water was added after cooling to room temperature, the pH was adjusted to ~10 by addition of solid sodium bicarbonate and the aqueous solution was washed 2x with MTB-ether. The aqueous layer was then adjusted to pH ~2 by addition of 2 M hydrochloric acid and extracted 3x with ethyl acetate. The combined organic layer was washed with brine, dried over magnesium sulfate and concentrated in vacuum to afford 123 mg of the title compound of the formula
Figure imgf000471_0001
as a yellow solid.
1H-NMR (CDCl3, TMS) δ (ppm) : 6.43 (2H, br s), 7.75 (IH, s), 10.53 (IH, br s) .
Step 5: Preparation of N'- (4 , 6-dibromo-3- { [5-bromo-2- (3- chloro-pyridin-2-yl) -2H-pyrazole-3-carbonyl] -amino}- pyridine-2-carbonyl) -N'-ethyl-hydrazinecarboxylic acid methyl ester (16)
5-Bromo-2- (3-chloro-pyridin-2-yl) -2H-pyrazole-3-carboxylic acid (example 1, step 5) (126 mg) was suspended in acetonitrile (1 mL) and pyridine (55 μL) and methanesulfonyl chloride (40 μL) were added. The reaction mixture was stirred for 30 min at room temperature, 3- amino-4, 6-dibromo-pyridine-2-carboxylic acid (123 mg) in acetonitrile (1 mL) and pyridine (115 μL) was added and the reaction mixture was stirred 1 h at room temperature. Methanesulfonyl chloride (40 μL) was added and the reaction mixture was stirred for 13 h at room temperature. The reaction mixture was concentrated in vacuum, the residue was suspended in NMP (1 mL) , W-ethyl-hydrazinecarboxylic acid methyl ester (237 mg, step 2) was added and the reaction mixture was stirred for 1 h at 800C. Water was added after cooling to room temperature and the mixture was 2x extracted with ethyl acetate. The combined organic layer was washed 4x with water, washed with brine, dried over magnesium sulfate and concentrated in vacuum. The residue was purified by column chromatography (silica 60, chloroform/ethyl acetate = 10:1, then 5:1, then 3:1, Rf = 0.25 in chloroform/ethyl acetate = 3:1) to afford 90 mg of a white solid. The compound was purified again by column chromatography (silica 60, hexane/ethyl acetate = 1:1, Rf = 0.20) to afford 60 mg of compound 16 of the present invention of the formula
Figure imgf000473_0001
as a white solid. 1H-NMR (CDCl3, TMS) δ (ppm) : 1.02-1.16' (3.OH, m) , 3.67-3.90 (5.0H, m) , 6.98 (0.5H, s), 7.18 (1.5H, s) , 7.41 (1.0H, dd, J = 8 Hz, 5 Hz), 7.68 (1.0H, s), 7.88 (1.0H, dd, J = 8 Hz, 2 Hz), 8.47 (1.0H, dd, J= 5 Hz, 2 Hz), 9.32-9.53 (1.0H, m) ,
Example 15: Preparation of N'- (2- { [2- (3-chloro-pyridin-2- yl) -5-trifluoromethyl-2E-pyrazole-3-carbonyl] -amino} - pyridine-3- carbonyl) -hydrazinecarboxylic acid methyl ester (17)
Step 1: Preparation of 2- [2- (3-chloro-pyridin-2-yl) -5- trif luoroπtethyl-2ff-pyrazol-3-yl ] -pyrido [ 2 , 3-d] [ 1 , 3 ] oxazin-
4 -one
5-Trifluoromethyl-2- (3-chloro-pyridin-2-yl) -2H-pyrazole-3- carboxylic acid chloride (example 2, step 3) (800 mg) was added to a mixture of 2-aminonicotinic acid (356 mg) in acetonitrile (20 mL) . The mixture was stirred for 10 minutes at room temperature and triethylamine (360 μL) was added and stirred for 15 minutes, before a second portion of triethylamine (720 μL) was added. After the mixture was stirred for further 15 minutes at room temperature, methanesulfonyl chloride (220 μL) was added. After stirring for 1.5 hours at room temperature, the reaction was quenched with water and extracted 2x with ethyl acetate, washed with brine, dried over MgSO4 and concentrated in vacuum. The residue was purified by column chromatography (silica 60, chloroform/ethyl acetate = 1:1, Rf = 0.40) to afford 660 mg of the title compound of the formula
Figure imgf000474_0001
as beige solid.
1H-NMR (CDCl3, TMS) δ (ppm) : 7.49 (IH, dd, J= 8 Hz, 5 Hz), 7.56 (IH, dd, J= 8 Hz, 5 Hz), 7.62 (IH, s), 8.02 (IH, dd, J = 8 Hz, 2 Hz), 8.50 (IH, dd, J= 8 Hz, 2 Hz), 8.56 (IH, dd, J= 5 Hz, 2 Hz), 8.94 (IH, dd, J= 5 Hz, 2 Hz).
Step 2: Preparation of N'- (2- { [2- (3-chloro-pyridin-2-yl) - 5-trifluoromethyl-2ff-pyrazole-3-carbonyl] -amino} -pyridine- 3-carbonyl) -hydrazinecarboxylic acid methyl ester (17) 2- [2- (3-Chloro-pyridin-2-yl) -5-trifluoromethyl-2H-pyrazol- 3-yl] -pyrido [2, 3-d] [1, 3] oxazin-4-one (292 mg) was dissolved in DMF (18 mL) , carbazaic acid methyl ester (667 mg) was added and the solution was stirred for 16 hours at room temperature. The reaction mixture was quenched with water and extracted with MTB-ether. The organic layer was washed 3x with water, washed with brine, dried over MgSC>4 and concentrated in vacuum. The residue was purified by column chromatography (silica 60, chloroform/methanol = 20:1, Rf = 0.15) to afford 157 mg of compound 17 of the present invention of the formula
Figure imgf000475_0001
as a white solid.
1H-NMR (DMSO-D6) δ (ppm) : 3.48-3.64 (3H, br m) , 7.38 (IH, br s) , 7.67-7.69 (2H, m) , 8.07 (IH, br s) , 8.24 (IH, dd, J
= 8 Hz, 1 Hz) , 8.52-8.56 (2H, m) , 9.31 (IH, br s) , 10.43 (IH, br s) , 11.48 (IH, br s) .
Example 16: Preparation of N'- (3- { [5-bromo-2- (3-chloro- pyridin -2-yl) -2H~pyrazole-3-carbonyl] -amino} -4-methyl- thiophene-2-carbonyl) -hydrazinecarboxylic acid methyl ester (18)
Step 1: Preparation of 2- [5-bromo-2- (3-chloro-pyridin-2-yl) -2ff-pyrazol-3-yl] -7-methyl- thieno [3, 2-d] [1, 3] oxazin-4-one A mixture of 3-bromo-l- (3-chloro-2-pyridinyl) -lH-pyrazole - 5-carboxylic acid (example 1, step 5) (600 mg) and thionyl chloride (2 ml) was heated to reflux for 2 hours. The reaction mixture was allowed to cool to room temperature and concentrated under reduced pressure. The resulting residue was dissolved in acetonitrile (10 mL) and 3-amino-4-methyl-thiophene-2- carboxylic acid (310 mg) was added. The mixture was stirred at room temperature for 30 minutes. Then, triethylamine (200 mg) was added to the mixture. After stirring the mixture at room temperature for 30 minutes, a second portion of triethylamine (400 mg) was added and the mixture was stirred at room temperature for 30 minutes. Methanesulfonyl chloride (500 mg) was added and the mixture was stirred at room temperature for 6 hours. Water was poured into the reaction mixture and the mixture was concentrated under reduced pressure. The resulting residue was washed with water and MTB-ether to afford 0.72 g of the title compound of the formula
Figure imgf000477_0001
1H-NMR (DMSO-D6) δ (ppm) : 1.74 (3H, br s) , 7.52-7.57 (IH, ~m) , 7.74-7.80 (IH, in) , 8.02 (IH, br s) , 8.30-8.37 (IH, m) ,
8.60-8.64 (IH, m) .
Step 2: Preparation of N'- (3- { [5-bromo-2- (3-chloro-pyridin -2-yl) -2H-pyrazole-3-carbonyl] -amino} -4-methyl-thiophene-2- carbonyl) -hydrazinecarboxylic acid methyl ester (18) A mixture of 2- [5-bromo-2- (3-chloro-pyridin-2-yl) -2H- pyrazol -3-yl] -7-methyl-thieno [3, 2-d] [1, 3] oxazin-4-one
(210 mg), carbazaic acid methyl ester (450 mg) and DMF (10 mL) was stirred at room temperature for 10 hours. The reaction mixture was quenched with water and the mixture was extracted with ethyl acetate. The organic layer was washed with water, dried over sodium sulfate and concentrated under reduced pressure. The resulting residue was subjected to silica gel column chromatography to afford 120 mg of compound 18 of the present invention of the formula :
Figure imgf000478_0001
1H-NMR (DMSO-D6) δ (ppm) : 1.96-2.01 (3H, m) , 3.58-3.65 (3H, m) , 7.38-7.47 (2H, m) , 7.62 (IH, dd, J = 8 Hz," 5 Hz), 8.16- 8.23 (IH, m) , 8.50 (IH, d, J = 4 Hz) , 9.24 (IH, br s), 9.83 (IH, br s) , 10.28 (IH, br s)
Example 17: Preparation of N'- (5- { [5-broπιo-2- (3-chloro- pyridin -2-yl) -2E-pyrazole-3-carbonyl] -amino} -1-methyl-IH- pyrazole-4-carbonyl) -hydrazinecarboxylic acid methyl ester (19)
Step 1: Preparation of 6- [5-bromo-2- (3-chloro-pyridin-2-yl) -2H-pyrazol-3-yl] -1-methyl-lH-pyrazolo [3, 4-d] [1,3] oxazin-4- one A mixture of 3-bromo-l- (3-chloro-2-pyridinyl) -IH-pyrazole - 5-carboxylic acid (example 1, step 5) (1.10 g) and thionyl chloride (4 mL) was heated to reflux for 2 hours. The reaction mixture was allowed to cool to room temperature, and concentrated under reduced pressure. The resulting residue was dissolved in acetonitrile (10 mL) and of 5- amino-l-methyl-lH-pyrazole-4- carboxylic acid (520 mg) was 4.78
added. The mixture was stirred at room temperature for 30 minutes. Then, triethylamine (400 mg) was added to the mixture. After stirring at room temperature for 30 minutes, a second portion of triethylamine (800 mg) was added and the mixture was stirred at room temperature for 30 minutes. Methanesulfonyl chloride (600 mg) of was added, and the mixture was stirred at room temperature for 6 hours. Water was poured into the reaction mixture and the mixture was concentrated under reduced pressure. The resulting residue was washed with water and MTB-ether to afford 900 mg of the title compound of the formula
Figure imgf000479_0001
1H-NMR (DMSO-D6) δ (ppm) : 3.46 (3H, s), 7.60 (IH, s), 7.78 (IH, dd, J = 8 Hz, 5 Hz), 8.24 (IH, s), 8.35 (IH, d, J = 8 Hz), 8.63 (IH, d, J= 5 Hz).
Step 2: Preparation of N'- (5- { [5-bromo-2- (3-chloro-pyridin -2-yl) -2H-pyrazole-3-carbonyl] -amino} -1-methyl-lfl-pyrazole- 4-carbonyl) -hydrazinecarboxylic acid methyl ester (19) A mixture of 6- [3-brom.o-l- (3-chloro-2-pyridinyl) -lH-pyrazol -5-yl] -1-methyl- IH-pyrazolo [3, 4-d] [1, 3] oxazin-4-one (300 mg) , carbazaic acid methyl ester (700 mg) and DMF (10 mL) was stirred at room temperature for 10 hours. The reaction mixture was quenched with water and the mixture was extracted with ethyl acetate. The organic layer was washed with water, dried over sodium sulfate, and concentrated under reduced pressure. The resulting residue was subjected to silica gel column chromatography to afford 200 mg of compound 19 of the present invention of the formula
Figure imgf000480_0001
1H-NMR (DMSO-D6) δ (ppm) : 3.55-3.60 (6H, m) , 7.48 (IH, s),
7.64 (IH, dd, J= 8 Hz, 5 Hz), 7.96 (IH, s) , 8.20 (IH, d, J
= 8 Hz), 8.52 (IH, d, J = 5 Hz), 9.08 (IH, br s) , 9.86 (IH, br s) , 10.79 (IH, br s)
Example 18: Preparation of N'- (6- { [2- (3-chloro-pyridin-2- yl) -5-trifluoromethyl-2fl-pyrazole-3-carbonyl] -amino} -5- methyl-2-trifluoromethyl-quinoline-7-carbonyl) - hydrazinecarboxylic acid methyl ester (20)
Step 1: Preparation of 5-oxo-2-trifluoromethyl-5, 6, 7 , 8- tetra hydro-quinoline-7-carboxylic acid methyl ester
A solution of 3, 5-dioxo-cyclohexanecarboxylic acid methyl ester (3.6 g, preparation as described in J. Chem. Soc, Perkin Trans. 1 (1976), (13), 1382-4.), (Z) -amino-1, 1, 1- trifluoro -but-3-en-2-one (2.94 g, prepared as described in EP 744400 (1996)), trifluoroacetic acid (1.21 g) and ammonium trifluoroacetate (1.39 g) in toluene (50 mL) are heated at reflux temperature in a Dean-Stark apparatus. After reaction completion, the reaction mixture is cooled, diluted with ethyl acetate and washed successively with saturated aqueous sodium bicarbonate and water. The organic phase is dried over anhydrous sodium sulfate, filtered and concentrated in vacuum. The residue is purified by column chromatography (eluting with hexane/ethyl acetate = 4:1) to give 1.5 g of the title compound of the formula
Figure imgf000481_0001
Step 2: Preparation of 5-hydroxy-2-trifluoromethyl- quinoline -7-carboxylic acid methyl ester
A solution of 5-oxo-2-trifluoromethyl-5, 6, 7 , 8-tetrahydro- quinoline-7-carboxylic acid methyl ester (50.0 g) is dissolved in methylene chloride (500 mL) and treated drop wise with a solution of bromotrichloromethane (54.43 g) and 1, 8-diazabicylo [5.4.0] undec-7-en (55.72 g) in methylene chloride (100 mL) at 0-50C. After the addition is complete, the reaction mixture is allowed to warm to room temperature, and stirred for 1 h. The reaction mixture is diluted with ethyl acetate and then washed successively with diluted aqueous hydrochloric acid and brine. The ethyl acetate phase is dried over anhydrous sodium sulfate, filtered and concentrated in vacuum. The residue is purified by recrystallization from hexane/ethyl acetate to give 47.13 g of the title compound of the formula
Figure imgf000482_0001
as pale yellow crystals.
Step 3: Preparation of 5-hydroxy-6-nitro-2-trifluoromethyl- quinoline-7-carboxylic acid methyl ester 5-Hydroxy-2-trifluoromethyl-quinoline -7-carboxylic acid methyl ester (46.0 g) is dissolved in concentrated sulfuric acid (200 mL, 97%) at 0-50C. To this cooled solution is added drop wise fuming nitric acid (7 mL, 100%) . After the addition is complete, the reaction mixture is allowed to warm to room temperature. TLC analysis (hexane/ethyl acetate = 4:1) after 30 min shows reaction completion. The reaction mixture is slowly poured onto an ice/water mixture (ca. 2 mL) and the crystals were filtered off, washed thoroughly with water and dried in vacuum to afford 47.0 g of the title compound of the formula
Figure imgf000483_0001
Step, 4j Preparation of 6-nitro-5- trifluoromethanesulfonyloxy -2-trifluoromethyl-quinoline-7- carboxylic acid methyl ester
A ' solution of 5-hydroxy-6-nitro-2-trifluoromethyl- quinoline- 7-carboxylic acid methyl ester (6.82 g) in methylene chloride (50 mL) is treated with triethylamne
(6.69 g) and a catalytic amount of 4-dimethylamino pyridine
(0.2.6 g) . To this solution is added trifluoromethanesulfonic anhydride (9.1 g) , maintaining the temperature at 250C for 1 h. The reaction mixture is diluted with methylene chloride and then washed successively with diluted aqueous hydrochloric acid, water, saturated aqueous sodium bicarbonate and water. The methylene chloride phase is dried over anhydrous sodium sulfate, filtered and concentrated in vacuum. The residue is purified by column chromatography (hexane/ethyl acetate = 9:1) to give 6.6 g of the title compound of the formula
Figure imgf000484_0001
as pale yellow crystals.
Step 5: Preparation of 5-methyl-6-nitro-2-trifluoromethyl- quinoline-7-carboxylic acid methyl ester
A suspension of indium trichloride (2.0 g) in dry THF (5 mL) under an argon atmosphere is cooled to -780C and then treated drop wise with methyl magnesium chloride (9.1 mL, 3 M in THF) . The milky suspension is allowed to warm to room temperature and then added drop wise to a refluxing solution of bis (triphenylphosphine) palladium ( II ) chloride (0.19 g) and β-nitro-5-trifluoromethanesulfonyloxy-2- trifluoromethyl- quinoline-7-carboxylic acid methyl ester (4.05 g) in dry THF (35 mL) . The mixture is refluxed under an argon atmosphere, monitoring by TLC. After reaction completion, the reaction mixture is concentrated in vacuum, the residue is taken up in diethyl ether and washed successively with diluted hydrochloric acid and brine. The diethyl ether phase is dried over anhydrous sodium sulfate, filtered and concentrated in vacuum. The residue is purified by column chromatography (hexane/ethyl acetate = 4:1) to give 2.0 g of the title compound of the formula
Figure imgf000485_0001
Step 6: Preparation of 5-methyl-6-nitro-2-trifluoromethyl- quinoline-7-carboxylic acid
5-Methyl-6-nitro-2-trifluoromethyl-quinoline-7-carboxylic acid methyl ester (3.78 g) is dissolved in 200 inL of methanol/water (3:1 mixture) and treated with lithium hydroxide hydrate (1.06 g) at room temperature. After reaction completion, the mixture is poured into ethyl acetate and 2 N hydrochloric acid, the organic phase is washed 3x with water, dried over sodium sulfate, filtered and concentrated in vacuum. The residue is triturated with a small amount of hexane . Filtration gives 3.50 g of the title compound of the formula
Figure imgf000485_0002
Step 7 : Preparation of 6-amino-5-methyl-2-trifluoromethyl- quinoline-7-carboxylic acid
A solution of 5-methyl-6-nitro-2-trifluoromethyl- quinoline-7-carboxylic acid (1.40 g) in ethanol (100 itiL) is hydrogenated at atmosphere pressure and ambient temperature in the presence of Raney-nickel catalyst. TLC analysis after 12 h shows reaction completion. The mixture is filtered over hyflo and the filtrate concentrated in vacuum. The residue is recrystallized from hexane/ethyl acetate to give 0.90 g of the title compound of the formula
Figure imgf000486_0001
Step 8: Preparation of 2- [2- (3-chloro-pyridin-2-yl) -5- trifluoromethyl-2H-pyrazol-3-yl] -9-methyl-6- trifluoromethyl-3-oxa-l, 5-diaza-anthracen-4-one
A solution of 6-amino-5-methyl-2-trifluoromethyl-quinoline- 7-carboxylic acid (0.60 g) , 2- (3-chloro-pyridin-2-yl) -5- trifluoromethyl-2fl-pyrazole-3-carboxylic acid (0.65 g, example 2, step 2) and pyridine (0.79 g) in acetonitrile (30 mli) is cooled to 0-50C and treated drop wise with methane sulfonyl chloride (0.89 g) dissolved in 2 mL acetonitrile. TLC analysis (hexane/ethyl acetate 4:1) after 2 h shows reaction completion. The reaction mixture is concentrated to 2/3 of the original volume in vacuum and poured onto 75 mL of ice/water. The resultant crystals are filtered off, washed with water and dried in vacuum to give 1.0 g of the title compound of the formula
Figure imgf000487_0001
as orange crystals.
Step 9: Preparation of N'- ( 6- { [2- (3-chloro-pyridin-2-yl) - 5-trifluoromethyl-2if-pyrazole-3-carbonyl] -amino} -5-methyl- 2-trifluoromethyl-quinoline-7-carbonyl) -hydrazinecarboxylic acid methyl ester (20) 2- [2- (3-Chloro-pyridin-2-yl) -5-trifluoromethyl-2Jf-pyrazol- 3-yl] -9-methyl-6-trifluoromethyl-3-oxa-l, 5-diaza-anthracen- 4-one (600 mg, can be prepared as in WO 2007/020050) is suspended in DMF and carbazaic acid methyl ester (1.18 g) is added. The solution is stirred for 15 h at 500C before it is quenched with water. The mixture is 2x extracted with ethyl acetate, the combined organic layer is 3x washed with water, washed with brine, dried over magnesium sulfate and concentrated in vacuum. The residue is purified by column chromatography to afford the title compound of the formula
Figure imgf000488_0001
Then, Formulation Examples will be^shown. All parts are by weight.
Formulation Example 1
Into a mixture of 35 parts of xylene and 35 parts of N, N-dimethylformamide, 10 parts of any one of the present compounds (1) to (19) is dissolved, and then 14 parts of polyoxyethylene styrylphenyl ether and 6 parts of calcium dodecylbenzenesulfonate are added. The mixture is stirred thoroughly to obtain a 10% emulsion.
Formulation Example 2
To a mixture of 4 parts of sodium laurylsulfate, 2 parts of calcium ligninsulfonate, 20 parts of synthetic hydrous silicon oxide fine powder and 54 parts of diatomaceous earth, 20 parts of any one of the present compounds (1) to (19) is added. The mixture is stirred thoroughly to obtain a 20% wettable agent. Formulation Example 3
To 2 parts of any one of the present compounds (1) to (19), 1 part of synthetic hydrous silicon oxide fine powder, 2 parts of calcium ligninsulfonate, 30 parts of bentonite and 65 parts of kaolin clay are added, and then stirred thoroughly. Then, an appropriate amount of water is added to the mixture. The mixture is further stirred, granulated with a granulator, and forced-air dried to obtain a 2% granule.
Formulation Example 4
Into an appropriate amount of acetone, 1 part of any one of the present compounds (1) to (19) is dissolved, and then 5 parts of synthetic hydrous silicon oxide fine powder,
0.3 part of PAP and 93.7 parts of fubasami clay are added.
The mixture is stirred thoroughly. Then, acetone is removed from the mixture by evaporation to obtain a 1% powder .
Formulation Example 5
A mixture of 10 parts of any one of the present compounds (1) to (19) ; 35 parts of white carbon containing
50 parts of polyoxyethylene alkyl ether sulfate ammonium salt; and 55 parts of water is finely ground by a wet grinding method to obtain a 10% flowable agent.
Formulation Example 6
In 5 parts of xylene and 5 parts of trichloroethane, 0.1 part of any one of the present compounds (1) to (19) is dissolved. The solution is mixed with 89.9 parts of deodorized kerosene to obtain a 0.1% oil.
Formulation Example 7 In 0.5 ml of acetone, 10 mg of any one of the present compounds (1) to (19) is dissolved. The solution is mixed uniformly with 5 g of a solid feed powder for an animal (solid feed powder for rearing and breeding CE-2, manufactured by CLEA Japan, Inc.), and then dried by evaporation of acetone to obtain poison bait.
Then, it will be shown by Test Examples that the present compound is effective in controlling harmful arthropods. In the Test Example, a controlling values were calculated by the following equation:
Controlling value (%) = U-(Cb * Tai)/(Cai x Tb)) x 100 wherein,
Cb: the number of worms in a non-treated section before treatment Cai : the number of worms in a non-treated section on observation
Tb: the number of worms in a treated-section before treatment
Tai : the number of worms in a treated-section on observation.
Test Example 1
Preparations of the test compounds obtained in Formulation Example 5 were diluted with water so that the active ingredient concentration became 500 ppm, to prepare test spray solutions.
At the same time, cabbage was planted in a polyethylene cup, and grown until the third true leaf or the fourth true leaf was developed. The test spray solution as described above was sprayed in an amount of 20 ml/cup on the cabbage.
After the spray solution on the cabbage was dried, 10 third-instar larvae of diamondback moths (Plutella xylostella) were put on the cabbage. After 5 days, the number of diamondback moths was counted, and the controlling value was calculated by the above equation.
As a result, the test spray solutions of the present compounds (1), (2), (3), (4), (5), (7), (8), (9), (10), (11), (14), (15), (16), (17) and (19) each exhibited a controlling value of 90% or more. Furthermore, preparations of the test compound (7) and a comparative compound of the formula:
Figure imgf000492_0001
(WO2002/070483A) obtained in a formulation according to Formulation Example 5 were diluted with water so that the active ingredient concentration became 0.2 ppm, to prepare test spray solution. At the same time, cabbage was planted in a polyethylene cup, and grown until the third true leaf or the fourth true leaf was developed. The test spray solution as described above was sprayed in an amount of 20 ml/cup on the cabbage. After the spray solution on the cabbage was dried, 10 third-instar larvae of diamondback moths (Plutella xylostella) were put on the cabbage. After 5 days, the number of diamondback moths was counted, and the controlling value was calculated by the above equation. Compound (7) exhibited a control value of more than 80%, whereas the comparison compound of the above formula exhibited less than 80% control. Test Example 2
Preparations of the test compounds obtained in Formulation Example 5 were diluted with water so that the active ingredient concentration became 500 ppm to prepare test spray solutions.
At the same time, cucumber was planted in a polyethylene cup, and was grown until the first true leaf was developed. About 30 cotton aphids were put on the cucumber. One day after, the test spray solution as described above was sprayed in an amount of 20 ml/cup on the cucumber. Six days after spraying, the number of cotton aphids (Aphis gossypii) was counted, and a controlling value was calculated by the above equation.
As a result, the test spray solutions of the present compounds (1), (2), (3), (4), (5), (7), (8), (9), (10), (11), (14), (15), (16), (18) and (19) each exhibited a controlling value of 90% or more.
Test Example 3 Preparations of the test compounds obtained in
Formulation Example 5 were diluted with water so that the active ingredient concentration became 500 ppm to prepare test spray solutions .
At the same time, cabbage was planted in a polyethylene cup, and grown until the third true leaf or the fourth true leaf was developed. The test spray solution as described above was sprayed in an amount of 20 ml/cup on the cabbage. After the spray solution sprayed on the cabbage was dried, 10 fourth-instar larvae of Spodoptera litura were put on the cabbage. After 5 days, the number of Spodoptera litura surviving on the cabbage leaves was counted, and a controlling value was calculated by the above equation.
As a result, the test spray solutions of the present compounds (1), (3), (4), (5), (7), (8), (9), (10), (11), (14), (15), (16) and (17) each exhibited a controlling value of 80% or more.
Test Example 4 Preparations of the test compounds obtained in
Formulation Example 5 were diluted with water so that the active ingredient concentration became 500 ppm to prepare test spray solutions.
At the same time, 20 ml of the test spray solution as described above was sprayed to an apple seedling (28 day- old seeding, tree height: about 15 cm) planted in a plastic cup. The apple seedling was air-dried to such an extent that the spray solution sprayed on the apple seedling was dried, about 30 first-instar larvae of Adoxophyes orana fasciata were released. Seven days after spraying, the number of worms surviving on the apple seedling was counted, and a controlling value was calculated by the above equation.
As a result, the test spray solutions of the present compounds (1), (2), (3), (4), (5), (7), (8), (14), (15) and (19) each exhibited a controlling value of 90% or more.
Test Example 5
Preparations of the test compounds obtained in Formulation Example 5 was diluted with water so that the active ingredient concentration became 500 ppm to prepare test spray solutions.
At the same time, cucumber was planted in a polyethylene cup, and was grown until the first true leaf was developed. The test spray solution as described above was sprayed in an amount of 20 ml/cup on the cucumber. After the spray solution on the cucumber was dried, the first true leaf was cut and then placed on a filter paper (diameter: 70 mm) containing water in a polyethylene cup (diameter: 110 mm) . On the cucumber leaf, 20 larvae of Franklinella occidentalis were released, and the polyethylene cup was capped. Seven days after spraying, the percentage of leaf area damaged by the insect was examined. As a result, the test spray solutions of the present compounds (1), (2), (3), (4), (7), (8), (9), (10), (11), (14), (15) and (16) each suppressed the feeding damage to the level of damaged area of 5% or less.
Test Example 6
Preparations of the test compounds obtained in Formulation Example 5 was diluted with water so that the active ingredient concentration became 500 ppm to prepare test spray solutions. At the same time, cabbage was planted in a polyethylene cup, and grown until the first true leaf was developed. All leaves excluding the first true leaf were cut off. On the first true leaf, adults of silver leaf whitefly, Bemisia argentifolii (or biotype B of tobacco whitefly, Bemisia tabaci) were released and allowed to lay eggs for about 24 hours. The cabbage was retained in a greenhouse for 8 days. When larvae hatched from the laid eggs, the test spray solution as described above was sprayed in an amount of 20 ml/cup to the cabbage. Seven days after spraying, the number of larvae surviving on the cabbage was counted, and a controlling value was calculated by the above equation.
As a result, the test spray solutions of the present compounds (7), (8), (9), (10), (11), (14) and (15) each exhibited a controlling value of 90% or more. Industrial applicability
According to the present invention, since the hydrazide compound of the present invention has excellent effipacy of controlling pests, it is useful as an active ingredient of a pesticide.

Claims

1. A hydrazide compound represented by the formula (I), an N-oxide thereof or suitable salt thereof:
Figure imgf000498_0001
wherein,
A1 and A2 independently represent an oxygen atom or a sulfur atom;
E represents, together with the two contiguous linking carbon atoms, a 5- or 6-membered heteroaromatic ring system or a 8, 9 or 10-membered fused heterobicyclic ring system
R1 represents a hydrogen atom, C1-C6 alkyl optionally substituted with one or more halogen atoms, C2-C6 cyanoalkyl, C1-C6 hydroxyalkyl, C2-C6 alkoxyalkyl optionally substituted with one or more halogen atoms, C2- C6 alkenyl optionally substituted with" one or more halogen atoms, C2-C6 alkynyl optionally substituted with one or more halogen atoms, C3-C6 cycloalkyl optronally substituted with one or more halogen atoms, C1-C6.alkylthio optionally substituted with one or more halogen atoms, Cl-Cβ alkylsulfinyl optionally substituted with one or more r halogen atoms, C1-C6 alkylsulfonyl optionally substituted with one or more halogen atoms, C2-C6 alkylcarbonyl optionally substituted with one or more halogen atoms, C2- Cβ alkoxycarbonyl, C2-C6 alkylaminocarbonyl, C3-C8 dialkylaminocarbonyl, C4-C6 cycloalkylaminocarbonyl, or C3- C6 trialkylsilyl; or represents phenyl, C7-C9 phenylalkyl or phenylcarbonyl : each said phenyl ring optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) hydroxyl, (5) carboxyl, (6) C1-C6 alkyl optionally substituted with one or more halogen atoms, (7) C1-C6 hydroxyalkyl, (8) C1-C6 alkoxy optionally substituted with one or more halogen atoms, (9) C2-C6 cyanoalkyl, (10) C2-C6 alkoxyalkyl optionally substituted with one or more halogen atoms, (11) C2-C6 alkenyl optionally substituted with one or more halogen atoms, (12) C2-C6 alkynyl optionally substituted with one or more halogen atoms, (13) C3-C6 cycloalkyl optionally substituted with one or more halogen atoms, (14) C1-C6 alkylthio optionally substituted with one or more halogen atoms, (15) C1-C6 alkylsulfinyl optionally substituted with one or more halogen atoms, (16) C1-C6 alkylsulfonyl optionally substituted with one or more halogen atoms, (17) C1-C6 alkylamino, (18) C2-C8 dialkylamino, (19) C3-C6 cycloalkylamino, (20) C2-C6 alkylcarbonyl, (21) C2-C6 alkoxycarbonyl, (22) C2-C6 alkylaminocarbonyl, (23) C3-C8 dialkylaminocarbonyl, (24) C4-C6 cycloalkylaminocarbonyl and (25) C3-C6 trialkylsilyl,
R2 and R3 independently represent a hydrogen atom, Cl- C6 alkyl optionally substituted with one or more halogen atoms, C2-C6 cyanoalkyl, C1-C6 hydroxyalkyl, C2-C6 alkoxyalkyl optionally substituted with one or more halogen atoms, C2-C6 alkenyl optionally substituted with one or more halogen atoms, C2-C6 alkynyl optionally substituted with one or more halogen atoms, C3-C6 cycloalkyl optionally substituted with one or more halogen atoms, C1-C6 alkylthio optionally substituted with one or more halogen atoms, Cl- C6 alkylsulfinyl optionally substituted with one or more halogen atoms, C1-C6 alkylsulfonyl optionally substituted with one or more halogen atoms, C2-C6 alkylcarbonyl optionally substituted with one or more halogen atoms, C2- C6 alkoxycarbonyl, C2-C6 alkylaminocarbonyl, C3-C8 dialkylaminocarbonyl, C4-C6 cycloalkylaminocarbonyl, or C3- C6 trialkylsilyl; or represents phenyl, C7-C9 phenylalkyl or phenylcarbonyl : each said phenyl ring optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) hydroxyl, (5) carboxyl, (6) C1-C6 alkyl optionally substituted with one or more halogen atoms, (7) C1-C6 hydroxyalkyl, (8) C1-C6 alkoxy optionally substituted with one or more halogen atoms, (9) C2-C6 cyanoalkyl, (10) C2-C6 alkoxyalkyl optionally substituted with one or more halogen atoms, (11) C2-C6 alkenyl optionally substituted with one or more halogen atoms, (12) C2-C6 alkynyl optionally substituted with one or more halogen atoms, (13) C3-C6 cycloalkyl optionally substituted with one or more halogen atoms, (14) C1-C6 alkylthio optionally substituted with one or more halogen atoms, (15) C1-C6 alkylsulfinyl optionally substituted with one or more halogen atoms, (16) C1-C6 alkylsulfonyl optionally substituted with one or more halogen atoms, (17) C1-C6 alkylamino, (18) C2-C8 dialkylamino, (19) C3-C6 cycloalkylamino, (20) C2-C6 alkylcarbonyl, (21) C2-C6 alkoxycarbonyl, (22) C2-C6 alkylaminocarbonyl, (23) C3-C8 dialkylaminocarbonyl, (24) C4-C6 cycloalkylaminocarbonyl and (25) C3-C6 trialkylsilyl; or
R2 and R3 are taken together with the two nitrogen atoms to which they are attached to form a 5 to 8 membered ring containing two nitrogen atoms, one or more CH2 or C (=0) , and optionally one or two ring members selected from the group consisting of (1) an oxygen atom, (2) a sulfur atom, (3) S(=0), (4) S(=0)2 and (4) NRa (wherein Ra represents C1-C6 alkyl optionally substituted with one or more halogen atoms, C2-C6 alkoxycarbonyl optionally substituted with one or more halogen atoms, or a phenyl optionally substituted with one or more independent substituents from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) C1-C6 'alkyl optionally substituted with one or more halogen atoms, (5) C1-C6 alkoxy optionally substituted with one or more halogen atoms, (6) C1-C6 alkylthio optionally substituted with one or more halogen atoms, (7) Cl-Cβ alkylsulfinyl optionally substituted with one or more halogen atoms, (8) C1-C6 alkylsulfonyl optionally substituted with one or more halogen atoms, (9) C1-C6 alkylamino optionally substituted with one or more halogen atoms, (10) C2-C6 dialkylamino optionally substituted with one or more halogen atoms, (11) C2-C6 alkylcarbonyl optionally substituted with one or more halogen atoms, (12) C2-C6 alkoxycarbonyl optionally substituted with one or more halogen atoms, (13) C2-C6 alkylaminocarbonyl optionally substituted with one or more halogen atoms and (14) C3-C6 dialkylaminocarbonyl optionally substituted with one or more halogen atoms); and wherein the ring at the carbon atoms is optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) C1-C6 alkyl optionally substituted with one or more halogen atoms, and (3) C2-C6 alkoxycarbonyl optionally substituted with one or more halogen atoms;
R4 represents a halogen atom, cyano, nitro, hydroxyl, carboxyl, C1-C6 alkyl optionally substituted with one or more halogen atoms, C1-C6 alkoxy optionally substituted with one or more halogen atoms, C2-C6 cyanoalkyl, C2-C6 alkoxyalkyl optionally substituted with one or more halogen atoms, C2-C6 alkenyl optionally substituted with one or more halogen atoms, C2-C6 alkynyl optionally substituted with one or more halogen atoms, C3-C6 cycloalkyl optionally substituted with one or more halogen atoms, C1-C6 alkylthio optionally substituted with one or more halogen atoms, Cl- C6 alkylsulfinyl optionally substituted with one or more halogen atoms, C1-C6 alkylsulfonyl optionally substituted with one or more halogen atoms, C1-C6 alkylamino, C2-C8 dialkylamino, C3-C6 cycloalkylamino, C2-C6 alkylcarbonyl optionally substituted with one or more halogen atoms, C2- C6 alkoxycarbonyl, C2-C6 alkylaminocarbonyl, C3-C8 dialkylaminocarbonyl, or C3-C6 trialkylsilyl; or represents a phenyl, benzyl, phenoxy, or a 5- or 6- membered heteroaromatic ring, each ring optionally substituted with one or more substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) hydroxyl, (5) carboxyl, (6) C1-C6 alkyl optionally substituted with one or more halogen atoms, (7) C1-C6 hydroxyalkyl, (8) C1-C6 alkoxy optionally substituted with one or more halogen atoms, (9) C2-C6 cyanoalkyl, (10) C2-C6 alkoxyalkyl optionally substituted with one or more halogen atoms, (11) C2-C6 alkenyl optionally substituted with one or more halogen atoms, (12) C2-C6 alkynyl optionally substituted with one or more halogen atoms, (13) C3-C6 cycloalkyl optionally substituted with one or more halogen atoms, (14) C1-C6 alkylthio optionally substituted with one or more halogen atoms, (15) C1-C6 alkylsulfinyl optionally substituted with one or more halogen atoms, (16) C1-C6 alkylsulfonyl optionally substituted with one or more halogen atoms, (17) C1-C6 alkylamino, (18) C2-C8 dialkylamino, (19) C3-C6 cycloalkylamino, (20) C2-C6 alkylcarbonyl, (21) C2-C6 alkoxycarbonyl, (22) C2-C6 alkylaminocarbonyl, (23) C3-C8 dialkylaminocarbonyl, (24) C4-C6 cycloalkylaminocarbonyl and (25) C3-C6 trialkylsilyl,
n represents an integer of 0 to 3 (provided that, when n is an integer of 2 or more, R4's may be the same or different) ; Q represents Ql, Q2 , Q3, Q4, Q5 or Q6:
Ql : C(=A31)— R6
Q2 : C(=A32)— OR7
Q3 : C(=A33)— SR8
Q4 : C(=A34)— NR9R10
Q5 ; S(O)-R11
Q6 : S(O)Sr-NR12R13 ,
A31, A32, A33 and A34 represent an oxygen atom, or a sulfur atom; m represents an integer of 0 to 2
R6 represents a hydrogen atom; C2-C6 alkenyl optionally substituted with one or more halogen atoms; C2- C6 alkynyl optionally substituted with one or more halogen atoms; C1-C6 alkyl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) C1-C6 alkoxy optionally substituted with one or more halogen atoms, (3) C1-C6 alkylthio optionally substituted with one or more halogen atoms, (4) C1-C6 alkylsulfinyl optionally substituted with one or more halogen atoms, (5) C1-C6 alkylsulfonyl optionally substituted with one or more halogen atoms, (6) C2-C6 dialkylamino optionally substituted with one or more halogen atoms, and (7) C3-C6 cycloalkyl optionally substituted with one or more halogen atoms; C3-C6 cycloalkyl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, and (2) C1-C6 alkyl optionally substituted with one or more halogen atoms; phenyl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) C1-C6 alkyl optionally substituted with one or more halogen atoms, (5) Cl-Cβ alkoxy optionally substituted with one or more halogen atoms, (6) C1-C6 alkylthio optionally substituted with one or more halogen atoms, (7) C1-C6 alkylsulfinyl optionally substituted with one or more halogen atoms, (8) C1-C6 alkylsulfonyl optionally substituted with one or more halogen atoms, (9) C1-C6 alkylamino optionally substituted with one or more halogen atoms, (10) C2-C6 dialkylamino optionally substituted with one or more halogen atoms, (11) C2-C6 alkylcarbonyl optionally substituted with one or more halogen atoms, (12) C2-C6 alkoxycarbonyl optionally substituted with one or more halogen atoms, (13) C2-C6 alkylaminocarbonyl optionally substituted with one or more halogen atoms and (14) C3-C6 dialkylaminocarbonyl optionally substituted with one or more halogen atoms; naphthyl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) C1-C6 alkyl optionally substituted with one or more halogen atoms and (5) C1-C6 alkoxy optionally substituted with one or more halogen atoms; 5- to 6-membered heteroaryl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) C1-C6 alkyl optionally substituted with one or more halogen atoms and (5) Cl-Cβ alkoxy optionally substituted with one or more halogen atoms; 3- to 8-membered non-aromatic heterocyclic ring optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, and (2) C1-C6 alkyl optionally substituted with one or more halogen atoms; C7-C9 phenylalkyl or C7-C9 phenoxyalkyl : each said phenyl ring optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) C1-C6 alkyl optionally substituted with one or more halogen atoms and (5) C1-C6 alkoxy optionally substituted with one or more halogen atoms,
R7 and R8 represent C1-C6 alkyl optionally substituted with one or more halogen atoms; C2-C6 alkoxyalkyl optionally substituted with one or more halogen atoms; C2- C6 alkenyl optionally substituted with one or more halogen atoms; C2-C6 alkynyl optionally substituted with one or more halogen atoms; C3-C6 cycloalkyl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, and (2) C1-C6 alkyl optionally substituted with one or more halogen atoms; phenyl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) C1-C6 alkyl optionally substituted with one or more halogen atoms, (5) C1-C6 alkoxy optionally substituted with one or more halogen atoms, (6) C1-C6 alkylthio optionally substituted with one or more halogen atoms, (7) C1-C6 alkylsulfinyl optionally substituted with one or more halogen atoms, (8) C1-C6 alkylsulfonyl optionally substituted with one or more halogen atoms, (9) C1-C6 alkylamino optionally substituted with one or more halogen atoms, (10) C2-C6 dialkylamino optionally substituted with one or more halogen atoms, (11) C2-C6 alkylcarbonyl optionally substituted with one or more halogen atoms, (12) C2-C6 alkoxycarbonyl optionally substituted with one or more halogen atoms, (13) C2-C6 alkylaminocarbonyl optionally substituted with one or more halogen atoms and (14) C3-C6 dialkylaminocarbonyl optionally substituted with one or more halogen atoms; 5- to 6-membered heteroaryl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) Cl-Cβ alkyl optionally substituted with one or more halogen atoms and (5) C1-C6 alkoxy optionally substituted with one or more halogen atoms; or C7-C9 phenylalkyl whose phenyl ring moiety optionally is substituted with one or more independent substituents selected from the group consisting of (1) a' halogen atom, (2) cyano, (3) nitro, (4) C1-C6 alkyl optionally substituted with one or more halogen atoms and (5) C1-C6 alkoxy optionally substituted with one or more halogen atoms,
R9 and R10 independently represent a hydrogen atom; Cl- Cβ alkyl optionally substituted with one or more halogen atoms; C2-C6 alkoxyalkyl optionally substituted with one or more halogen atoms; C2-C6 alkenyl optionally substituted with one or more halogen atoms; C2-C6 alkynyl optionally substituted with one or more halogen atoms; C3-C6 cycloalkyl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, and (2) C1-C6 alkyl optionally substituted with one or more halogen atoms; phenyl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) C1-C6 alkyl optionally substituted with one or more halogen atoms, (5) Cl-Cβ alkoxy optionally substituted with one or more halogen atoms, (6) C1-C6 alkylthio optionally substituted with one or more halogen atoms, (7) C1-C6 alkylsulfinyl optionally substituted with one or more halogen atoms, (8) C1-C6 alkylsulfonyl optionally substituted with one or more halogen atoms, (9) C1-C6 alkylamino optionally substituted with one or more halogen atoms, (10) C2-C6 dialkylamino optionally substituted with one or more halogen atoms, (11) C2-C6 alkylcarbonyl optionally substituted with one or more halogen atoms, (12) C2-C6 alkoxycarboriyl optionally substituted with one or more halogen atoms, (13) C2-C6 alkylaminocarbonyl optionally substituted with one or more halogen atoms and (14) C3-C6 dialkylaminocarbonyl optionally substituted with one or more halogen atoms; 5- to 6-membered heteroaryl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) C1-C6 alkyl optionally substituted with one or more halogen atoms and (5) C1-C6 alkoxy optionally substituted with one or more halogen atoms; or C7-C9 phenylalkyl whose phenyl ring moiety optionally is substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) C1-C6 alkyl optionally substituted with one or more halogen atoms and (5) C1-C6 alkoxy optionally substituted with one or more halogen atoms, R11 represents C1-C6 alkyl optionally substituted with one or more halogen atoms; C3-C6 cycloalkyl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, and (2) C1-C6 alkyl optionally substituted with one or more halogen atoms; or a phenyl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) C1-C6 alkyl optionally substituted with one or more halogen atoms and (5) Cl-Cβ alkoxy optionally substituted with one or more halogen atoms; 5- to 6-membered heteroaryl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) C1-C6 alkyl optionally substituted with one or more halogen atoms and (5) C1-C6 alkoxy optionally substituted with one or more halogen atoms; or 3- to 8-membered non-aromatic heterocyclic ring optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, and (2) Cl-Cβ alkyl optionally substituted with one or more halogen atoms,
R12 and R13 independently represent C1-C6 alkyl optionally substituted with one or more halogen atoms; C3- Cβ cycloalkyl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, and (2) C1-C6 alkyl optionally substituted with one or more halogen atoms; or phenyl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) Cl-Cβ alkyl optionally substituted with one or more halogen atoms and (5) C1-C6 alkoxy optionally substituted with one or more halogen atoms;
J represents Jl or J2 :
Figure imgf000512_0001
Xa, Ya, Za, Xb, Yb and Zb independently represent CH or a nitrogen atom;
R19a and R19b represent a hydrogen atom; C1-C6 alkyl optionally substituted with one or more halogen atoms; C2- C6 cyanoalkyl, C2-C6 alkoxyalkyl optionally substituted with one or more halogen atoms; C2-C6 alkenyl optionally substituted with one or more halogen atoms; C2-C6 alkynyl optionally substituted with one or more halogen atoms; C3- C6 cycloalkyl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, and (2) Cl-Cβ alkyl optionally substituted with one or more halogen atoms; phenyl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) C1-C6 alkyl optionally substituted with one or more halogen atoms, (5) C1-C6 alkoxy optionally substituted with one or more halogen atoms, (6) C1-C6 alkylthio optionally substituted with one or more halogen atoms, (7) C1-C6 alkylsulfinyl optionally substituted with one or more halogen atoms, (8) C1-C6 alkylsulfonyl optionally substituted with one or more halogen atoms, (9) C1-C6 alkylamino optionally substituted with one or more halogen atoms, (10) C2-C6 dialkylamino optionally substituted with one or more halogen atoms, (11) C2-C6 alkylcarbonyl optionally substituted with one or more halogen atoms, (12) C2-C6 alkoxycarbonyl optionally substituted with one or more halogen atoms, (13) C2-C6 alkylaminocarbonyl optionally substituted with one or more halogen atoms and (14) C3-C6 dialkylaminocarbonyl optionally substituted with one or more halogen atoms; 5- to 6-membered heteroaryl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) C1-C6 alkyl optionally substituted with one or more halogen atoms, (5) C1-C6 alkoxy optionally substituted with one or more halogen atoms, (6) Cl-Cβ alkylthio optionally substituted with one or more halogen atoms, (7) C1-C6 alkylsulfinyl optionally substituted with one or more halogen atoms, (8) C1-C6 alkylsulfonyl optionally- substituted with one or more halogen atoms, (9) C1-C6 alkylamino optionally substituted with one or more halogen atoms, (10) C2-C6 dialkylamino optionally substituted with one or more halogen atoms, (11) C2-C6 alkylcarbonyl optionally substituted with one or more halogen atoms, (12) C2-C6 alkoxycarbonyl optionally substituted with one or more halogen atoms, (13) C2-C6 alkylaminocarbonyl optionally substituted with one or more halogen atoms and (14) C3-C6 dialkylaminocarbonyl optionally substituted with one or more halogen atoms; C7-C9 phenylalkyl whose phenyl ring is optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) C1-C6 alkyl optionally substituted with one or more halogen atoms, (5) C1-C6 alkoxy optionally substituted with one or more halogen atoms, (6) C1-C6 alkylthio optionally substituted with one or more halogen atoms, (7) C1-C6 alkylsulfinyl optionally substituted with one or more halogen atoms, (8) C1-C6 alkylsulfonyl optionally substituted with one or more halogen atoms, (9) C1-C6 alkylamino optionally substituted with one or more halogen atoms, (10) C2-C6 dialkylamino optionally substituted with one or more halogen atoms, (11) C2-C6 alkylcarbonyl optionally substituted with one or more halogen atoms, (12) C2-C6 alkoxycarbonyl optionally substituted with one or more halogen atoms, (13) C2-C6 alkylaminocarbonyl optionally substituted with one or more halogen atoms and (14) C3-C6 dialkylaminocarbonyl optionally substituted with one or more halogen atoms; or C7-C9 pyridinylalkyl whose pyridine ring is optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) C1-C6 alkyl optionally substituted with one or more halogen atoms, (5) C1-C6 alkoxy optionally substituted with one or more halogen atoms, (6) C1-C6 alkylthio optionally substituted with one or more halogen atoms, (7) C1-C6 alkylsulfinyl optionally substituted with one or more halogen atoms, (8) C1-C6 alkylsulfonyl optionally substituted with one or more halogen atoms, (9) C1-C6 alkylamino optionally substituted with one or more halogen atoms, (10) C2-C6 dialkylamino optionally substituted with one or more halogen atoms, (11) C2-C6 alkylcarbonyl optionally substituted with one or more halogen atoms, (12) C2-C6 alkoxycarbonyl optionally substituted with one or more halogen atoms, (13) C2-C6 alkylaminocarbonyl optionally substituted with one or more halogen atoms and (14) C3-C6 dialkylaminocarbonyl optionally substituted with one or more halogen atoms,
R20a and R20b represent a halogen atom; cyano; nitro; thiocyanato; C1-C6 alkyl optionally substituted with one or more halogen atoms; C1-C6 alkoxy optionally substituted with one or more halogen atoms; C2-C6 cyanoalkyloxy; C2-C6 alkoxyalkyloxy optionally substituted with one or more halogen atoms; C2-C6 alkenyloxy optionally substituted with one or more halogen atoms; C2-C6 alkynyloxy optionally substituted with one or more halogen atoms; C1-C6 alkylthio optionally substituted with one or more halogen atoms; Cl- C6 alkylsulfinyl optionally substituted with one or more halogen atoms; C1-C6 alkylsulfonyl optionally substituted with one or more halogen atoms; phenyl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) C1-C6 alkyl optionally substituted with one or more halogen atoms and (5) C1-C6 alkoxy optionally substituted with one or more halogen atoms; 5- to 6-membered heteroaryl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) C1-C6 alkyl optionally substituted with one or more halogen atoms and (5) C1-C6 alkoxy optionally substituted with one or more halogen atoms; or phenoxy optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) C1-C6 alkyl optionally substituted with one or more halogen atoms and (5) C1-C6 alkoxy optionally substituted with one or more halogen atoms,
p represents an integer of 0 to 3 (provided that, when p is an integer of 2 or 3, two or more R20a's may be the same or different) ;
q represents an integer of 0 to 3 (provided that, when q is an integer of 2 or 3, two or more R20b's may be the same or different) .
2. The compound according to claim 1, wherein E is 5- or 6-membered heteroaromatic ring.
3. The compound according to claim 1 or 2, wherein A1 and A2 are oxygen atoms,
R1 is a hydrogen atom or alkyl optionally substituted with one or more halogen atoms .
4. The compound according to claim 1, 2 or 3, wherein J is J-I.1, J-I.2, J-2.1, J-2.2 or J-2.3:
Figure imgf000518_0001
wherein R19a and R19b represent a hydrogen atom; C1-C6 alkyl optionally substituted with one or more halogen atoms; C3-C6 cycloalkyl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom and (2) C1-C6 alkyl optionally substituted with one or more halogen atoms; phenyl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) Cl-Cβ alkyl optionally substituted with one or more halogen atoms, (5) C1-C6 alkoxy optionally substituted with one or more halogen atoms, (6) C1-C6 alkylthio optionally substituted with one or more halogen atoms, (7) C1-C6 alkylsulfinyl optionally substituted with one or more halogen atoms, (8) C1-C6 alkylsulfonyl optionally substituted with one or more halogen atoms, (9) C1-C6 alkylamino optionally substituted with one or more halogen atoms, (10) C2-C6 dialkylamino optionally substituted with one or more halogen atoms, (11) C2-C6 alkylcarbonyl optionally substituted with one or more halogen atoms, (12) C2-C6 alkoxycarbonyl optionally substituted with one or more halogen atoms, (13) C2-C6 alkylaminocarbonyl optionally substituted with one or more halogen atoms and (14) C3-C6 dialkylaminocarbonyl optionally substituted with one or more halogen atoms; 5- to 6-membered heteroaryl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) Cl-Cβ alkyl optionally substituted with one or more halogen atoms and (5) C1-C6 alkoxy optionally substituted with one or more halogen atoms;
R20a and R20b represent a halogen atom, cyano , Cl-C β alkyl optionally substituted with one or more halogen atoms, C1-C6 alkoxy optionally substituted with one or more halogen atoms, C2-C6 cyanoalkyloxy, C2-C6 alkoxyalkyloxy optionally substituted with one or more halogen atoms, C2- C6 alkenyloxy optionally substituted with one or more halogen atoms, C1-C6 alkylthio optionally substituted with one or more halogen atoms, C1-C6 alkylsulfinyl optionally substituted with one or more halogen atoms, C1-C6 alkylsulfonyl optionally substituted with one or more halogen atoms, or phenyl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) C1-C6 alkyl optionally substituted with one or more halogen atoms and (5) Cl-Cβ alkoxy optionally substituted with one or more halogen atoms;
5- to 6-membered heteroaryl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) C1-C6 alkyl optionally substituted with one or more halogen atoms and (5) C1-C6 alkoxy optionally substituted with one or more halogen atoms or phenoxy optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) C1-C6 alkyl optionally substituted with one or more halogen atoms and (5) C1-C6 alkoxy optionally substituted with one or more halogen atoms; p represents an integer of 0 to 3, and q represents an integer of 0 to 3 (provided that, when p is an integer of 2 or 3, two or more R20a's may be the same or different and, when q is an integer of 2 or 3, two or more R20b's may be the same or different) .
5. The compound according to any of claim 1 to 4, an W- oxide thereof or suitable salt thereof, wherein Q is Ql, A31 is oxygen and
R6 represents a hydrogen atom; C1-C6 alkyl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) C1-C6 alkoxy optionally substituted with one or more halogen atoms, (3) C1-C6 alkylthio optionally substituted with one or more halogen atoms, (4) C1-C6 alkylsulfinyl optionally substituted with one or more halogen atoms, (5) C1-C6 alkylsulfonyl optionally substituted with one or more halogen atoms, (6) C2-C6 dialkylamino optionally substituted with one or more halogen atoms, and (7) C3-C6 cycloalkyl optionally substituted with one or more halogen atoms;
C3-C6 cycloalkyl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, and (2) Cl-Cβ alkyl optionally substituted with one or more halogen atoms; phenyl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) C1-C6 alkyl optionally substituted with one or more halogen atoms, (5) C1-C6 alkoxy optionally substituted with one or more halogen atoms, (6) C1-C6 alkylthio optionally substituted with one or more halogen atoms, (7) CΪ-C6 alkylsulfinyl optionally substituted with one or more halogen atoms, (8) C1-C6 alkylsulfonyl optionally substituted with one or more halogen atoms, (9) C1-C6 alkylamino optionally substituted with one or more halogen atoms, (10) C2-C6 dialkylamino optionally substituted with one or more halogen atoms, (11) C2-C6 alkylcarbonyl optionally substituted with one or more halogen atoms, (12) C2-C6 alkoxycarbonyl optionally substituted with one or more halogen atoms, (13) C2-C6 alkylaminocarbonyl optionally substituted with one or more halogen atoms and (14) C3-C6 dialkylaminocarbonyl optionally substituted with one or more halogen atoms;
5- to 6-membered heteroaryl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) C1-C6 alkyl optionally substituted with one or more halogen atoms and (5) C1-C6 alkoxy optionally substituted with one or more halogen atoms;
3- to 8-membered non-aromatic heterocyclic optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, and (2) C1-C6 alkyl optionally substituted with one or more halogen atoms or C7-C9 phenylalkyl or C7-C9 phenoxyalkyl : each said phenyl ring optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) C1-C6 alkyl optionally substituted with one or more halogen atoms and (5) C1-C6 alkoxy optionally substituted with one or more halogen atoms .
6. The compound according to claim 5, wherein A1 and A2 are oxygen atoms .
7. The compound according to any of claim 1 to 4, an W- oxide thereof or suitable salt thereof, wherein Q is Q2, A32 is oxygen and
R7 is C1-C6 alkyl optionally substituted with one or more halogen atoms; C2-C6 alkenyl optionally substituted with one or more halogen atoms; C3-C6 cycloalkyl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, and (2) Cl-Cβ alkyl optionally substituted with one or more halogen atoms; phenyl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) Cl-Cβ alkyl optionally substituted with one or more halogen atoms, (5) Cl-Cβ alkoxy optionally substituted with one or more halogen atoms, (6) Cl-Cβ alkylthio optionally substituted with one or more halogen atoms, (7) Cl-C6 alkylsulfinyl optionally substituted with one or more halogen atoms, (8) C1-C6 alkylsulfonyl optionally substituted with one or more halogen atoms, (9) C1-C6 alkylamino optionally substituted with one or more halogen atoms, (10) C2-C6 dialkylamino optionally substituted with one or more halogen atoms, (11) C2-C6 alkylcarbonyl optionally substituted with one or more halogen atoms, (12) C2-C6 alkoxycarbonyl optionally substituted with one or more halogen atoms, (13) C2-C6 alkylaminocarbonyl optionally substituted with one or more halogen atoms and (14) C3-C6 dialkylaminocarbonyl optionally substituted with one or more halogen atoms;
5- to β-membered heteroaryl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) C1-C6 alkyl optionally substituted with one or more halogen atoms and (5) Cl-Cβ alkoxy optionally substituted with one or more halogen atoms or C7-C9 phenylalkyl whose ring moiety is optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) C1-C6 alkyl optionally substituted with one or more halogen atoms and (5) C1-C6 alkoxy optionally substituted with one or more halogen atoms .
8. The compound according to claim 7, wherein A1 and A2 are oxygen atoms .
9. The compound according to any of claim 1 to 4, an N- oxide thereof or suitable salt thereof, wherein Q is Q4 , A34 is oxygen and
R9 and R10 independently represent a hydrogen atom; C1-C6 alkyl optionally substituted with one or more halogen atoms; C3-C6 cycloalkyl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, and (2) C1-C6 alkyl optionally substituted with one or more halogen atoms; phenyl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) C1-C6 alkyl optionally substituted with one or more halogen atoms, (5) Cl-Cβ alkoxy optionally substituted with one or more halogen atoms, (6) C1-C6 alkylthio optionally substituted with one or more halogen atoms, (7) C1-C6 alkylsulfinyl optionally substituted with one or more halogen atoms, (8) C1-C6 alkylsulfonyl optionally substituted with one or more halogen atoms, (9) C1-C6 alkylamino optionally substituted with one or more halogen atoms, (10) C2-C6 dialkylamino optionally substituted with one or more halogen atoms, (11) C2-C6 alkylcarbonyl optionally substituted with one or more halogen atoms, (12) C2-C6 alkoxycarbonyl optionally substituted with one or more halogen atoms, (13) C2-C6 alkylaminocarbonyl optionally substituted with one or more halogen atoms and (14) C3-C6 dialkylaminocarbonyl optionally substituted with one or more halogen atoms; 5- to 6-membered heteroaryl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) C1-C6 alkyl optionally substituted with one or more halogen atoms and (5) C1-C6 alkoxy optionally substituted with one or more halogen atoms or C7-C9 phenylalkyl whose ring moiety is optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) Cl-Cβ alkyl optionally substituted with one or more halogen atoms and (5) C1-C6 alkoxy optionally substituted with one or more halogen atoms .
10. The compound according to claim 9, wherein A1 and A2 are oxygen atoms .
11. A hydrazide compound represented by the formula (II-l) or (II-2),
Figure imgf000527_0001
wherein,
Xa represents a nitrogen atom or CR 20ax,
Y and Z represent independently a nitrogen atom or CR4b, but not Y and Z are CR4b at the same time,
R1 represets a hydrogen atom or C1-C6 alkyl optionally substituted with one or more halogen atoms,
R2 and R3 independently represent a hydrogen atom, Cl- C6 alkyl optionally substituted with one or more halogen atoms, C2-C6 cyanoalkyl, C1-C6 hydroxyalkyl, C2-C6 alkoxyalkyl optionally substituted with one or more halogen atoms, C2-C6 alkenyl optionally substituted with one or more halogen atoms, C2-C6 alkynyl optionally substituted with one or more halogen atoms, C3-C6 cycloalkyl optionally substituted with one or more halogen atoms, C1-C6 alkylthio optionally substituted with one or more halogen atoms, Cl- Cβ alkylsulfinyl optionally substituted with one or more halogen atoms, C1-C6 alkylsulfonyl optionally substituted with one or more halogen atoms, C2-C6 alkylcarbonyl optionally substituted with one or more halogen atoms, C2- C6 alkoxycarbonyl, C2-C6 alkylaminocarbonyl, C3-C8 dialkylaminocarbonyl, C4-C6 cycloalkylaminocarbonyl, or C3- C6 trialkylsilyl; or represents phenyl, C7-C9 phenylalkyl or phenylcarbonyl : each said phenyl ring optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) hydroxyl, (5) carboxyl, (6) Cl-Cβ alkyl optionally substituted with one or more halogen atoms, (7) C1-C6 hydroxyalkyl, (8) C1-C6 alkoxy optionally substituted with one or more halogen atoms, (9) C2-C6 cyanoalkyl, (10) C2-C6 alkoxyalkyl optionally substituted with one or more halogen atoms, (11) C2-C6 alkenyl optionally substituted with one or more halogen atoms, (12) C2-C6 alkynyl optionally substituted with one or more halogen atoms, (13) C3-C6 cycloalkyl optionally substituted with one or more halogen atoms, (14) C1-C6 alkylthio optionally substituted with one or more halogen atoms, (15) C1-C6 alkylsulfinyl optionally substituted with one or more halogen atoms, (16) C1-C6 alkylsulfonyl optionally substituted with one or more halogen atoms, (17) C1-C6 alkylamino, (18) C2-C8 dialkylamino, (19) C3-C6 cycloalkylamino, (20) C2-C6 alkylcarbonyl, (21) C2-C6 alkoxycarbonyl, (22) C2-C6 alkylaminocarbonyl, (23) C3-C8 dialkylaminocarbonyl, (24)
C4-C6 cycloalkylaminocarbonyl and (25) C3-C6 trialkylsilyl; or
R2 and R3 are taken together with the two nitrogen atoms to which they are attached to form a 5 to 8 membered ring containing two nitrogen atoms, one or more CH2 or
C(=O), and optionally one or two ring members selected from the group consisting of (1) an oxygen atom, (2) a sulfur atom, (3) S(=O), (4) S(=O)2 and (4) NRa (wherein Ra represents C1-C6 alkyl optionally substituted with one or more halogen atoms, C2-C6 alkoxycarbonyl optionally substituted with one or more halogen atoms, or a phenyl optionally substituted with one or more independent substituents from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) C1-C6 alkyl optionally substituted with one or more halogen atoms, (5) C1-C6 alkoxy optionally substituted with one or more halogen atoms, (6) C1-C6 alkylthio optionally substituted with one or more halogen atoms, (7) C1-C6 alkylsulfinyl optionally substituted with one or more halogen atoms, (8) C1-C6 alkylsulfonyl optionally substituted with one or more halogen atoms, (9) C1-C6 alkylamino optionally substituted with one or more halogen atoms, (10) C2-C6 dialkylamino optionally substituted with one or more halogen atoms, (11) C2-C6 alkylcarbonyl optionally substituted with one or more halogen atoms, (12) C2-C6 alkoxycarbonyl optionally substituted with one or more halogen atoms, (13) C2-C6 alkylaminocarbonyl optionally substituted with one or more halogen atoms and (14) C3-C6 dialkylaminocarbonyl optionally substituted with one or more halogen atoms); and wherein the ring at the carbon atoms is optionally- substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) C1-C6 alkyl optionally substituted with one or more halogen atoms, and (3) C2-C6 alkoxycarbonyl optionally substituted with one or more halogen atoms; R4a, R4b and R4c independently represent a halogen atom, cyano, nitro, hydroxyl, carboxyl, C1-C6 alkyl optionally substituted with one or more halogen atoms, C2-C6 alkoxy optionally substituted with one or more halogen atoms, C2- C6 cyanoalkyl , C2-C6 alkoxyalkyl optionally substituted with one or more halogen atoms, C2-C6 alkenyl optionally substituted with one or more halogen atoms, C2-C6 alkynyl optionally substituted with one or more halogen atoms, C3- C6 cycloalkyl optionally substituted with one or more halogen atoms, C1-C6 alkylthio optionally substituted with one or more halogen atoms, C1-C6 alkylsulfinyl optionally substituted with one or more halogen atoms, Cl-Cβ alkylsulfonyl optionally substituted with one or more halogen atoms, Cl-Cβ alkylamino, C2-C8 dialkylamino, C3-C6 cycloalkylamino, C2-C6 alkylcarbonyl optionally substituted with one or more halogen atoms, C2-C6 alkoxycarbonyl, C2-C6 alkylaminocarbonyl, C3-C8 dialkylaminocarbonyl, C3-C6 trialkylsilyl; or represents independently phenyl, benzyl, phenoxy, or 5- or 6-membered heteroaromatic ring, each ring optionally substituted with one or more substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) hydroxyl, (5) carboxyl, (6) Cl-Cβ alkyl optionally substituted with one or more halogen atoms, (7) Cl-Cβ hydroxyalkyl, (8) C1-C6 alkoxy optionally substituted with one or more halogen atoms, (9) C2-C6 cyanoalkyl, (10) C2-C6 alkoxyalkyl optionally substituted with one or more halogen atoms, (11) C2-C6 alkenyl optionally substituted with one or more halogen atoms, (12) C2-C6 alkynyl optionally substituted with one or more halogen atoms, (13) C3-C6 cycloalkyl optionally substituted with one or more halogen atoms, (14) C1-C6 alkylthio optionally substituted with one or more halogen atoms, (15) C1-C6 alkylsulfinyl optionally substituted with one or more halogen atoms, (16) Cl-Cβ alkylsulfonyl optionally substituted with one or more halogen atoms, (17) C1-C6 alkylamino, (18) C2-C8 dialkylamino, (19) C3-C6 cycloalkylamino, (20) C2-C6 alkylcarbonyl, (21) C2-C6 alkoxycarbonyl, (22) C2-C6 alkylaminocarbonyl, (23) C3-C8 dialkylaminocarbonyl, (24) C4-C6 cycloalkylaminocarbonyl and (25) C3-C6 trialkylsilyl;
M is a hydrogen atom; C1-C6 alkyl optionally substituted witn^rle or more independent substituents selected from the group consisting of (1) a halogen atom, (2) C1-C6 alkoxy optionally substituted with one or more halogen atoms, (3) C1-C6 alkylthio optionally substituted with one or more halogen atoms, (4) C1-C6 alkylsulfinyl optionally substituted with one or more halogen atoms, (5) Cl-Cβ alkylsulfonyl optionally substituted with one or more halogen atoms, (6) C2-C6 dialkylamino optionally substituted with one or more halogen atoms, and (7) C3-C6 cycloalkyl optionally substituted with one or more halogen atoms; C1-C6 alkoxy optionally substituted with one or more halogen atoms; C1-C6 alkylthio optionally substituted with one or more halogen atoms; C1-C6 alkylamino; C2-C8 dialkylamino; phenyl, C7-C9 phenylalkyl or C7-C9 phenoxyalkyl : each said phenyl ring optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) C1-C6 alkyl optionally substituted with one or more halogen atoms, and (5) C1-C6 alkoxy optionally substituted with one or more halogen atoms;
5- to 6-membered heteroaryl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) C1-C6 alkyl optionally substituted with one or more halogen atoms, and (5) C1-C6 alkoxy optionally substituted with one or more halogen atoms; or 3- to 8-membered non-aromatic heterocyclic ring optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, and (2) C1-C6 alkyl optionally substituted with one or more halogen atoms; R19ax represents a hydrogen atom; C1-C6 alkyl optionally substituted with one or more halogen atoms; C2- C6 cyanoalkyl; C2-C6 alkoxyalkyl optionally substituted with one or more halogen atoms; C2-C6 alkenyl optionally substituted with one or more halogen atoms; C2-C6 alkynyl optionally substituted with one or more halogen atoms; C3- Cβ cycloalkyl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, and (2) C1-C6 alkyl optionally substituted with one or more halogen atoms; phenyl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) C1-C6 alkyl optionally substituted with one or more halogen atoms, (5) C1-C6 alkoxy optionally substituted with one or more halogen atoms, (6) C1-C6 alkylthio optionally substituted with one or more halogen atoms, (7) C1-C6 alkylsulfinyl optionally substituted with one or more halogen atoms, (8) C1-C6 alkylsulfonyl optionally substituted with one or more halogen atoms, (9) C1-C6 alkylamino optionally substituted with one or more halogen atoms, (10) C2-C6 dialkylamino optionally substituted with one or more halogen atoms, (11) C2-C6 alkylcarbonyl optionally substituted with one or more halogen atoms, (12) C2-C6 alkoxycarbonyl optionally substituted with one or more halogen atoms, (13) C2-C6 alkylaminocarbonyl optionally substituted with one or more halogen atoms and (14) C3-C6 dialkylaminocarbonyl optionally substituted with one or more halogen atoms; 5- to 6-membered heteroaryl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) C1-C6 alkyl optionally substituted with one or more halogen atoms, (5) C1-C6 alkoxy optionally substituted with one or more halogen atoms, (6) C1-C6 alkylthio optionally substituted with one or more halogen atoms, (7) C1-C6 alkylsulfinyl optionally substituted with one or more halogen atoms, (8) C1-C6 alkylsulfonyl optionally substituted with one or more halogen atoms, (9) C1-C6 alkylamino optionally substituted with one or more halogen atoms, (10) C2-C6 dialkylamino optionally substituted with one or more halogen atoms, (11) C2-C6 alkylcarbonyl optionally substituted with one or more halogen atoms, (12) C2-C6 alkoxycarbonyl optionally substituted with one or more halogen atoms, (13) C2-C6 alkylaminocarbonyl optionally substituted with one or more halogen atoms and
(14) C3-C6 dialkylaminocarbonyl optionally substituted with one or more halogen atoms; C7-C9 phenylalkyl whose phenyl ring is optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) C1-C6 alkyl optionally substituted with one or more halogen atoms, (5) C1-C6 alkoxy optionally substituted with one or more halogen atoms, (6) C1-C6 alkylthio optionally substituted with one or more halogen atoms, (7) C1-C6 alkylsulfinyl optionally substituted with one or more halogen atoms, (8) C1-C6 alkylsulfonyl optionally substituted with one or more halogen atoms, (9) C1-C6 alkylamino optionally substituted with one or more halogen atoms, (10) C2-C6 dialkylamino optionally substituted with one or more halogen atoms, (11) C2-C6 alkylcarbonyl optionally substituted with one or more halogen atoms, (12) C2-C6 alkoxycarbonyl optionally substituted with one or more halogen atoms, (13) C2-C6 alkylaminocarbonyl optionally substituted with one or more halogen atoms and (14) C3-C6 dialkylaminocarbonyl optionally substituted with one or more halogen atoms; or C7-C9 pyridinylalkyl whose pyridine ring is optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) C1-C6 alkyl optionally substituted with one or more halogen atoms, (5) C1-C6 alkoxy optionally substituted with one or more halogen atoms, (6) C1-C6 alkylthio optionally substituted with one or more halogen atoms, (7) C1-C6 alkylsulfinyl optionally- substituted with one or more halogen atoms, (8) C1-C6 alkylsulfonyl optionally substituted with one or more halogen atoms, (9) Cl-Cβ alkylamino optionally substituted with one or more halogen atoms, (10) C2-C6 dialkylamino optionally substituted with one or more halogen atoms, (11) C2-C6 alkylcarbonyl optionally substituted with one or more halogen atoms, (12) C2-C6 alkoxycarbonyl optionally substituted with one or more halogen atoms, (13) C2-C6 alkylaminocarbonyl optionally substituted with one or more halogen atoms and (14) C3-C6 dialkylaminocarbonyl optionally substituted with one or more halogen atoms;
R20ax, R20ay and R2Oaz represent a halogen atom; cyano; nitro; thiocyanato; C1-C6 alkyl optionally substituted with one or more halogen atoms; C1-C6 alkoxy optionally substituted with one or more halogen atoms; C2-C6 cyanoalkyloxy; C2-C6 alkoxyalkyloxy optionally substituted with one or more halogen atoms; C2-C6 alkenyloxy optionally substituted with one or more halogen atoms; C2-C6 alkynyloxy optionally substituted with one or more halogen atoms; C1-C6 alkylthio optionally substituted with one or more halogen atoms; C1-C6 alkylsulfinyl optionally substituted with one or more halogen atoms; C1-C6 alkylsulfonyl optionally substituted with one or more halogen atoms; phenyl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) C1-C6 alkyl optionally substituted with one or more halogen atoms and (5) C1-C6 alkoxy optionally substituted with one or more halogen atoms; 5- to 6-membered heteroaryl optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) C1-C6 alkyl optionally substituted with one or more halogen atoms and (5) C1-C6 alkoxy optionally substituted with one or more halogen atoms; or phenoxy optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) cyano, (3) nitro, (4) C1-C6 alkyl optionally substituted with one or more halogen atoms and (5) C1-C6 alkoxy optionally substituted with one or more halogen atoms.
12. The compound according to claim 11, wherein R1 is a hydrogen atom,
R2 is a hydrogen atom or C1-C6 alkyl optionally substituted with one or more halogen atoms, R3 is a hydrogen atom, C1-C6 alkyl optionally substituted with one or more halogen atoms or C2-C6 alkoxycarbonyl ,
R4a is a halogen atom or C1-C6 alkyl optionally substituted with one or more halogen atoms, R4c is a hydrogen atom, a halogen atom, cyano or Cl- C6 alkyl optionally substituted with one or more halogen atoms,
R19a is
Figure imgf000539_0001
wherein Xb is a nitrogen atom or CR21a,
R20ax and R20ay are independently a hydrogen atom, a halogen atom, C1-C6 alkyl optionally substituted with one or more halogen atoms, C1-C6 alkoxy optionally substituted with one or more halogen atoms or C1-C6 alkylthio optionally substituted with one or more halogen atoms, R20az is a hydrogen atom,
R21a, R21b and R21c are independently selected from the group consisting of a hydrogen atom, a halogen atom or Cl- C6 alkyl optionally substituted with one or more halogen atoms.
13. The compound according to claim 12, wherein Xa and Xb are nitrogen atoms,
Y is CH and Z is a nitrogen atom.
14. The compound according to claim 12, wherein Xa and Xb are nitrogen atoms,
Y is a nitrogen atom Z is CH and.
15. The compound according to claim 12, wherein R4b is a hydrogen atom.
16. The compound according to claim 15, wherein M is a hydrogen atom, C1-C6 alkyl, C1-C6 alkόxy, amino, C1-C6 alkylamino or C2-C8 dialkylamino.
17. The compound according to claim 16, wherein R2 is a hydrogen atom, methyl or ethyl,
R3 is a hydrogen atom, methyl, ethyl or methoxycarbonyl,
R4a is methyl, chloro, bromo or iodo,
R4c is hydrogen, fluoro, chloro, bromo, iodo or cyano,
R20ay is chloro, bromo, iodo, trifluoromethyl or pentafluoroethoxy, R22b is a hydrogen atom,
R22c is chloro or bromo,
M is hydrogen, methoxy, ethoxy, methylamino or dimethylamino .
18. The compound of claim 17, wherein R2 is a hydrogen atom,
R3 is methyl or ethyl and M is a hydrogen atom.
19. The compound of claim 18, wherein R2 and R3 are independently hydrogen, methyl or ethyl and M is methoxy or ethoxy.
20. A pesticide comprising the compound according to claim 1 as an active ingredient.
A method of controlling a pest which comprises applying the compound according to claim 1 directly to a pest, or to a place where a pest inhabits.
21. Use of the compound according to claim 1 for controlling a pest.
22. Use of the compound according to claim 1 for manufacturing a pesticidal preparation.
PCT/JP2008/057560 2007-04-12 2008-04-11 Heterocyclic hydrazide compound and pesticidal use of the same WO2008130021A2 (en)

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