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    • 专利摘要:
    [Object] To provide an aminopyrimidine derivative exhibiting a significant effect on a plant disease and a plant disease control agent for agricultural or horticultural use which contains as an active ingredient the aminopyrimidine derivative. [Solving Means] A plant disease control agent characterized by containing as an active ingredient one or more compounds selected from aminopyrimidine derivatives represented by General Formula [I]: [wherein R is a substituent such as a C2-10 alkyl group; R1 and R2 are each independently a hydrogen atom or a substituent such as an optionally substituted C1-10 alkyl group; X is a hydrogen atom or a substituent selected from a predefined substituent group; Y is a substituent selected from a predefined substituent group; and m is an integer from 0 to 3] and agriculturally acceptable salts thereof. [Effect] The agent solves problems of conventional plant disease control agents and further has excellent control effect, residual efficacy and the like.
    公开号:EP2006288A1
    申请号:EP07706978
    申请日:2007-01-18
    公开日:2008-12-24
    发明作者:Junichiro Bessho；Masao Nakatani；Yuuki Hirano；Hirokazu Arai；Atsushi Kogure；Norihisa Yonekura；Ryo Hanai
    申请人:Ihara Chemical Industry Co Ltd；Kumiai Chemical Industry Co Ltd；
    IPC主号:C07D-401
    专利说明:
    [0001] The present invention relates to a novel aminopyrimidine derivative and a plant disease control agent for agricultural or horticultural use. Background Art
    [0002] There has been reported in, for example, Patent Document 1, Patent Document 2, Patent Document 3, Patent Document 4 and Patent Document 5, that a certain type of aminopyrimidine derivatives has a disease control effect. However, the aminopyrimidine derivative described in a specification of the present application is not disclosed in these documents. Further, various aminopyrimidine derivatives have been synthesized and reported in Non-Patent Document 1 and the like, but there is no report related to the disease control effect. Patent Document 1: JP-A No. S54-115384 (Claims and others) Patent Document 2: JP-A No. S55-036402 (Claims and others) Patent Document 3: WO 2002/074753 (Claims and others) Patent Document 4: WO 2004/103978 (Claims and others) Patent Document 5: JP-A No. 2005-232081 (Claims and others) Non-Patent Document 1: Revista de Chimie, Vol. 38 No. 8, p. 674-679, 1987 Disclosure of the InventionProblems to be Solved by the Invention
    [0003] For growing agricultural and horticultural crops, many control agents have been used against crop diseases. However, with the traditional control agents, there had been cases where the control effect is insufficiently exhibited or its use is limited due to the emergence of pathogenic organism resistance to the drug, or phytotoxicity or contamination to plants is caused, or from the viewpoints of toxicity to man and beast and fishes and effect on environment, there are very few control agents that are satisfactory. Consequently, advent of a disease control agent that has few such defects and can be safely used has been demanded.
    [0004] An object of the invention is to provide a plant disease control agent that is free from the above-mentioned problems possessed by the traditional plant disease control agent and further has excellent control effect, residual efficacy and the like. Means for Solving the Problems
    [0005] Under these circumstances, the present inventors have conducted extensive studies on disease control effect and safety to crops and as a result, they found that a novel aminopyrimidine derivative has excellent disease control effect and safety to crops. Thus, they have completed the invention.
    [0006] That is, the invention provides the following (1) to (8):
    [0007] (1) a plant disease control agent for agricultural or horticultural use, which is characterized by containing as an active ingredient one or more compounds selected from aminopyrimidine derivatives represented by General Formula [I]:
    [0008]
    [0009] [whereinR is a C1-10 alkyl group, a C3-8 cycloalkyl group, a C3-8 cycloalkyl C1-3 alkyl group, a C1-6 haloalkyl group, a C2-6 alkenyl group, a C2-6 alkynyl group, a C3-8 cycloalkenyl group, a C1-6 acyl group, a C1-6 hydroxylalkyl group, a C1-6 alkoxy C1-6 alkyl group, a 1,3-dioxolan-2-yl group or a 1,3-dioxan-2-yl group;R1 and R2 are each independently a hydrogen atom, a C1-10 alkyl group which may be substituted with one or more substituents selected from Substituent Group α, a C1-10 alkoxy group which may be substituted with one or more substituents selected from Substituent Group α, a C3-8 cycloalkyl group, a C2-6 alkynyl group, a C2-6 alkenyl group, a C1-6 acyl group, a hydroxyl group, a C1-6 haloalkylcarbonyl group, a C1-6 alkoxycarbonyl group, a carbamoyl group, a mono(C1-6 alkyl) aminocarbonyl group, a di(C1-6 alkyl) aminocarbonyl group, a C1-6 alkylsulfonyl group, a C1-6 haloalkylsulfonyl group, a sulfamoyl group, a mono(C1-6 alkyl)aminosulfonyl group, or a di(C1-6 alkyl) aminosulfonyl group,while R1 and R2 may form a 5-membered or 6-membered ring (the 5-membered or 6-membered ring may be substituted with one or more substituents selected from Substituent Group α) with an atom arbitrarily selected from the group consisting of a carbon atom, an oxygen atom, a nitrogen atom and a sulfur atom, together with the nitrogen atom to which R1 and R2 are bonded;X is a hydrogen atom or a substituent selected from Substituent Group α;Y is a substituent selected from Substituent Group α; andm is an integer from 0 to 3,while Substituent Group α being defined as follows: "Substituent Group α": a halogen atom, a C1-10 alkyl group, a C3-8 cycloalkyl group, a C3-8 cycloalkyl C1-3 alkyl group, a C2-6 alkynyl group, a C2-6 alkenyl group, a C1-10 alkoxy group, a C1-6 alkoxy C1-3 alkyl group, a C3-8 cycloalkyloxy group, a C3-8 cycloalkyl C1-3 alkyloxy group, a C1-6 haloalkoxy group, a C2-6 alkynyloxy group, a C2-6 alkenyloxy group, a C1-6 haloalkyl group, a C1-6 alkylthio group, a C1-6 alkylsulfinyl group, a C1-6 alkylsulfonyl group, a C1-6 haloalkylthio group, a C1-6 haloalkylsulfinyl group, a C1-6 haloalkylsulfonyl group, a cyano group, an amino group, a nitro group, a hydroxyl group, a C1-6 hydroxylalkyl group, a mono(C1-6 alkyl)amino group, a di(C1-6 alkyl) amino group, a C1-6 acyl group, a carboxyl group, a C1-6 alkoxycarbonyl group, a carbamoyl group, a mono(C1-6 alkyl)aminocarbonyl group, a di(C1-6 alkyl)aminocarbonyl group, a thiol group, a thiocyanate group, a tri(C1-6 alkyl)silyl group, an optionally substituted benzyloxy group, a hydroxy-iminomethyl group, a C1-6 alkoxyiminomethyl group and an optionally substituted phenyl group] and agriculturally acceptable salts thereof;
    [0010] (2) an aminopyrimidine derivative represented by General Formula [I]:
    [0011]
    [0012] [whereinR is a C2-10 alkyl group, a C3-8 cycloalkyl group, a C3-8 cycloalkyl C1-3 alkyl group, a C1-6 haloalkyl group, a C2-6 alkenyl group, a C2-6 alkynyl group, a C3-8 cycloalkenyl group, a C1-6 acyl group, a C1-6 hydroxylalkyl group, a C1-6 alkoxy C1-6 alkyl group, a 1,3-dioxolan-2-yl group or a 1,3-dioxan-2-yl group;R1 and R2 are each independently a hydrogen atom, a C1-10 alkyl group which may be substituted with one or more substituents selected from Substituent Group α, a C1-10 alkoxy group which may be substituted with one or more substituents selected from Substituent Group α, a C3-8 cycloalkyl group, a C2-6 alkynyl group, a C2-6 alkenyl group, a C1-6 acyl group, a hydroxyl group, a C1-6 haloalkylcarbonyl group, a C1-6 alkoxycarbonyl group, a carbamoyl group, a mono(C1-6 alkyl)aminocarbonyl group, a di(C1-6 alkyl)aminocarbonyl group, a C1-6 alkylsulfonyl group, a C1-6 haloalkylsulfonyl group, a sulfamoyl group, a mono(C1-6 alkyl)aminosulfonyl group, or a di(C1-6 alkyl)aminosulfonyl group,while R1 and R2 may form a 5-membered or 6-membered ring (the 5-membered or 6-membered ring may be substituted with one or more substituents selected from Substituent Group α) with an atom arbitrarily selected from the group consisting of a carbon atom, an oxygen atom, a nitrogen atom and a sulfur atom, together with the nitrogen atom to which R1 and R2 are bonded;X is a hydrogen atom or a substituent selected from Substituent Group α;Y is a substituent selected from Substituent Group α; andm is an integer from 0 to 3,while Substituent Group α being defined as follows: "Substituent Group α": a halogen atom, a C1-10 alkyl group, a C3-8 cycloalkyl group, a C3-8 cycloalkyl C1-3 alkyl group, a C2-6 alkynyl group, a C2-6 alkenyl group, a C1-10 alkoxy group, a C1-6 alkoxy C1-3 alkyl group, a C3-8 cycloalkyloxy group, a C3-8 cycloalkyl C1-3 alkyloxy group, a C1-6 haloalkoxy group, a C2-6 alkynyloxy group, a C2-6 alkenyloxy group, a C1-6 haloalkyl group, a C1-6 alkylthio group, a C1-6 alkylsulfinyl group, a C1-6 alkylsulfonyl group, a C1-6 haloalkylthio group, a C1-6 haloalkylsulfinyl group, a C1-6 haloalkylsulfonyl group, a cyano group, an amino group, a nitro group, a hydroxyl group, a C1-6 hydroxylalkyl group, a mono(C1-6 alkyl)amino group, a di(C1-6 alkyl)amino group, a C1-6 acyl group, a carboxyl group, a C1-6 alkoxycarbonyl group, a carbamoyl group, a mono(C1-6 alkyl)aminocarbonyl group, a di(C1-6 alkyl)aminocarbonyl group, a thiol group, a thiocyanate group, a tri(C1-6 alkyl)silyl group, an optionally substituted benzyloxy group, a hydroxy-iminomethyl group, a C1-6 alkoxyiminomethyl group and an optionally substituted phenyl group] or an agriculturally acceptable salt thereof;
    [0013] (3) the aminopyrimidine derivative or an agriculturally acceptable salt thereof as described in (2),wherein, in General Formula [I],R1 is a hydrogen atom, a C1-10 alkyl group which may be substituted with one or more substituents selected from Substituent Group α, a C1-10 alkoxy group which may be substituted with one or more substituents selected from Substituent Group α, a C3-8 cycloalkyl group, a C2-6 alkynyl group, a C2-6 alkenyl group, a C1-6 acyl group, a hydroxyl group, a C1-6 haloalkylcarbonyl group, a C1-6 alkoxycarbonyl group, a carbamoyl group, a mono(C1-6 alkyl)aminocarbonyl group, a di(C1-6 alkyl)aminocarbonyl group, a C1-6 alkylsulfonyl group, a C1-6 haloalkylsulfonyl group, a sulfamoyl group, a mono(C1-6 alkyl)aminosulfonyl group or a di(C1-6 alkyl)aminosulfonyl group andR2 is a C1-10 alkyl group which may be substituted with one or more substituents selected from Substituent Group α, a C1-10 alkoxy group which may be substituted with one or more substituents selected from Substituent Group α, a C3-8 cycloalkyl group, a C2-6 alkynyl group, a C2-6 alkenyl group, a C1-6 acyl group, a C1-6 haloalkylcarbonyl group, a C1-6 alkoxycarbonyl group, a carbamoyl group, a mono(C1-6 alkyl) aminocarbonyl group, a di (C1-6 alkyl) aminocarbonyl group, a C1-6 alkylsulfonyl group, a C1-6 haloalkylsulfonyl group, a sulfamoyl group, a mono(C1-6 alkyl)aminosulfonyl group or a di(C1-6 alkyl)aminosulfonyl group,while R1 and R2 may form a 5-membered or 6-membered ring (the 5-membered or 6-membered ring may be substituted with one or more substituents selected from Substituent Group α) with an atom arbitrarily selected from the group consisting of a carbon atom, an oxygen atom, a nitrogen atom and a sulfur atom, together with the nitrogen atom to which R1 and R2 are bonded;
    [0014] (4) the aminopyrimidine derivative or an agriculturally acceptable salt thereof as described in (2),wherein, in General Formula [I],R1 is a C1-10 alkyl group which may be substituted with one or more substituents selected from Substituent Group β, a C1-10 alkoxy group which may be substituted with one or more substituents selected from Substituent Group α, a C3-8 cycloalkyl group, a C2-6 alkynyl group, a C2-6 alkenyl group, a C1-6 acyl group, a hydroxyl group, a C1-6 haloalkylcarbonyl group, a C1-6 alkoxycarbonyl group, a carbamoyl group, a mono(C1-6 alkyl)aminocarbonyl group, a di(C1-6 alkyl) aminocarbonyl group, a C1-6 alkylsulfonyl group, a C1-6 haloalkylsulfonyl group, a sulfamoyl group, a mono(C1-6 alkyl)aminosulfonyl group or a di(C1-6 alkyl)aminosulfonyl group andR2 is a hydrogen atom, a C1-10 alkyl group which may be substituted with one or more substituents selected from Substituent Group α, a C1-10 alkoxy group which may be substituted with one or more substituents selected from Substituent Group α, a C3-8 cycloalkyl group, a C2-6 alkynyl group, a C2-6 alkenyl group, a C1-6 acyl group, a C1-6 haloalkylcarbonyl group, a C1-6 alkoxycarbonyl group, a carbamoyl group, a mono(C1-6 alkyl)aminocarbonyl group, a di(C1-6 alkyl) aminocarbonyl group, a C1-6 alkylsulfonyl group, a C1-6 haloalkylsulfonyl group, a sulfamoyl group, a mono(C1-6 alkyl)aminosulfonyl group or a di(C1-6 alkyl)aminosulfonyl group,while R1 and R2 may form a 5-membered or 6-membered ring (the 5-membered or 6-membered ring is independently substituted with 1 to 4 halogen atoms or/and a C1-6 haloalkyl group) with an atom arbitrarily selected from the group consisting of a carbon atom, an oxygen atom, a nitrogen atom and a sulfur atom, together with the nitrogen atom to which R1 and R2 are bonded,where Substituent Group β being defined as follows: "Substituent Group β": a halogen atom, a C2-6 alkynyl group, a C3-8 cycloalkyloxy group, a C3-8 cycloalkyl C1-3 alkyloxy group, a C1-6 haloalkoxy group, a C2-6 alkynyloxy group, a C2-6 alkenyloxy group, a C1-6 haloalkyl group, a C1-6 alkylthio group, a C1-6 alkylsulfinyl group, a C1-6 alkylsulfonyl group, a C1-6 haloalkylthio group, a C1-6 haloalkylsulfinyl group, a C1-6 haloalkylsulfonyl group, a cyano group, a nitro group, a C1-6 acyl group, a carboxyl group, a C1-6 alkoxycarbonyl group, a carbamoyl group, a mono(C1-6 alkyl) aminocarbonyl group, a di(C1-6 alkyl)aminocarbonyl group and a tri(C1-6 alkyl)silyl group;
    [0015] (5) the aminopyrimidine derivative or an agriculturally acceptable salt thereof as described in (2),wherein, in General Formula [I],R1 is a hydrogen atom, a C1-10 alkyl group which may be substituted with one or more substituents selected from Substituent Group α, a C1-10 alkoxy group which may be substituted with one or more substituents selected from Substituent Group α, a C3-8 cycloalkyl group, a C2-6 alkynyl group, a C2-6 alkenyl group, a C1-6 acyl group, a hydroxyl group, a C1-6 haloalkylcarbonyl group, a C1-6 alkoxycarbonyl group, a carbamoyl group, a mono(C1-6 alkyl) aminocarbonyl group, a di(C1-6 alkyl)aminocarbonyl group a C1-6 alkylsulfonyl group, a C1-6 haloalkylsulfonyl group, a sulfamoyl group, a mono(C1-6 alkyl)aminosulfonyl group or a di(C1-6 alkyl)aminosulfonyl group andR2 is a hydrogen atom, a C1-10 alkyl group which may be substituted with one or more substituents selected from Substituent Group β, a C1-10 alkoxy group which may be substituted with one or more substituents selected from Substituent Group α, a C2-6 alkynyl group, a C1-6 acyl group, a C1-6 haloalkylcarbonyl group, a C1-6 alkoxycarbonyl group, a carbamoyl group, a mono(C1-6 alkyl)aminocarbonyl group, a di(C1-6 alkyl)aminocarbonyl group, a C1-6 alkylsulfonyl group, a C1-6 haloalkylsulfonyl group, a sulfamoyl group, a mono(C1-6 alkyl)aminosulfonyl group or a di(C1-6 alkyl)aminosulfonyl group,while R1 and R2 may form a 5-membered or 6-membered ring (the 5-membered or 6-membered ring is independently substituted with 1 to 4 halogen atoms or/and a C1-6 haloalkyl group) with an atom arbitrarily selected from the group consisting of a carbon atom, an oxygen atom, a nitrogen atom and a sulfur atom, together with the nitrogen atom to which R1 and R2 are bonded,where Substituent Group β being defined as follows: "Substituent Group β": a halogen atom, a C2-6 alkynyl group, a C3-8 cycloalkyloxy group, a C3-8 cycloalkyl C1-3 alkyloxy group, a C1-6 haloalkoxy group, a C2-6 alkynyloxy group, a C2-6 alkenyloxy group, a C1-6 haloalkyl group, a C1-6 alkylthio group, a C1-6 alkylsulfinyl group, a C1-6 alkylsulfonyl group, a C1-6 haloalkylthio group, a C1-6 haloalkylsulfinyl group, a C1-6 haloalkylsulfonyl group, a cyano group, a nitro group, a C1-6 acryl group, a carboxyl group, a C1-6 alkoxycarbonyl group, a carbamoyl group, a mono(C1-6 alkyl)aminocarbonyl group, a di(C1-6 alkyl)aminocarbonyl group and a tri(C1-6 alkyl)silyl group;
    [0016] (6) the aminopyrimidine derivative or an agriculturally acceptable salt thereof as described in (5),wherein, in General Formula [I],R2 is a C1-10 alkyl group which may be substituted with one or more substituents selected from Substituent Group β, a C1-10 alkoxy group which may be substituted with one or more substituents selected from Substituent Group α, a C2-6 alkynyl group, a C1-6 acyl group, a C1-6 haloalkylcarbonyl group, a C1-6 alkoxycarbonyl group, a carbamoyl group, a mono(C1-6 alkyl)aminocarbonyl group, a di(C1-6 alkyl)aminocarbonyl group, a C1-6 alkylsulfonyl group, a C1-6 haloalkylsulfonyl group, a sulfamoyl group, a mono(C1-6 alkyl)aminosulfonyl group or a di(C1-6 alkyl)aminosulfonyl group,while R1 and R2 may form a 5-membered or 6-membered ring (the 5-membered or 6-membered ring is independently substituted with 1 to 4 halogen atoms or/and a C1-6 haloalkyl group) with an atom arbitrarily selected from the group consisting of a carbon atom, an oxygen atom, a nitrogen atom and a sulfur atom, together with the nitrogen atom to which R1 and R2 are bonded;
    [0017] (7) a plant disease control agent for agricultural or horticultural use, which is characterized by containing as an active ingredient one or more compounds selected from the aminopyrimidine derivative as described in any one of (2) to (6) and an agriculturally acceptable salt thereof; and
    [0018] (8) a method of using an agent, which includes applying an effective amount of one or more compounds selected from the aminopyrimidine derivative as described in any one of (2) to (6) and an agriculturally acceptable salt thereof to target useful crops or soil, for protecting the useful crops from plant disease. Advantage of the Invention
    [0019] The aminopyrimidine derivative of the invention (hereinafter, referred to as 'compound of present application') is a novel compound known in literatures.
    [0020] The plant disease control agent for agricultural or horticultural use according to the invention has a high control effect on Pyricularia oryzae, Rhizoctonia solani, Erysiphe graminis, Septoria nodorum, Septoria tritici, Puccinia recondite, Pseudoperonospora cubensis, Botrytis cinerea, Colletotrichum lagenarium, Venturia inaequalis, Physalospora piricola, Plasmopara viticola and the like and further has a characteristic of exhibiting excellent residual efficacy and rain resistance without causing a crop damage. Thus, the agent is useful as a plant disease control agent for agricultural or horticultural use. Best Mode for Carrying out the Invention
    [0021] Definition of symbols and terms used in the present specification are shown below.
    [0022] The halogen atom represents a fluorine atom, a chlorine atom, a bromine atom, or an iodine atom.
    [0023] A notation such as C1-6 refers to a number of carbon atoms of the following substituent, which is from 1 to 6 in this case.
    [0024] The C1-6 alkyl group represents, unless otherwise particularly defined, a linear or branched chain alkyl group having 1 to 6 carbon atoms. Examples thereof may include groups such as methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl, 1-ethylpropyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, neopentyl, n-hexyl, 1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 1-ethylbutyl, 2-ethylbutyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 1, 3-dimethylbutyl, 2,2-dimethylbutyl, 2,3-dimethylbutyl, 3,3-dimethylbutyl, 1,1,2-trimethylpropyl, 1,2,2-trimethylpropyl, 1-ethyl-1-methylpropyl and 1-ethyl-2-methylpropyl,
    [0025] The C1-10 alkyl group represents, unless otherwise particularly defined, a linear or branched chain alkyl group having 1 to 10 carbon atoms. Examples thereof may include groups such as heptyl, 1-methylhexyl, 5-methylhexyl, 1,1-dimethylpentyl, 2,2-dimethylpentyl, 4,4-dimethylpentyl, 1-ethylpentyl, 2-ethylpentyl, 1,1,3-trimethylbutyl, 1,2,2-trimethylbutyl, 1,3,3-trimethylbutyl, 2,2,3-trimethylbutyl, 2,3,3-trimethylbutyl, 1-propylbutyl, 1,1,2,2-tetramethylpropyl, octyl, 1-methylheptyl, 3-methylheptyl, 6-methylheptyl, 2-ethylhexyl, 5,5-dimethylhexyl, 2,4,4-trimethylpentyl, 1-ethyl-1-methylpentyl, n-nonyl, 1-methyloctyl, 2-methyloctyl, 3-methyloctyl, 7-methyloctyl, 1-ethylheptyl, 1,1-dimethylheptyl, 6,6-dimethylheptyl, decyl, 1-methylnonyl, 2-methylnonyl, 6-methylnonyl, 1-ethyloctyl, 1-propylheptyl and n-decyl, in addition to the above examples of C1-6 alkyl group.
    [0026] The C3-8 cycloalkyl group represents, unless otherwise particularly defined, a cycloalkyl group having 3 to 8 carbon atoms. Examples thereof may include groups such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and cyclooctyl.
    [0027] The C3-8 cycloalkyl C1-3 alkyl group represents, unless otherwise particularly defined, a cycloalkyl-alkyl group where the cycloalkyl moiety has the same meanings as defined above and the alkyl moiety is a linear or branched chain alkyl group having 1 to 3 carbon atoms. Examples may include groups such as cyclopropylmethyl, 1-cyclopropylethyl, 2-cyclopropylethyl, 1-cyclopropylpropyl, 2-cyclopropylpropyl, 3-cyclopropylpropyl, cyclobutylmethyl, cyclopentylmethyl and cyclohexylmethyl.
    [0028] The C1-6 haloalkyl group represents, unless otherwise particularly defined, a linear or branched chain alkyl group having 1 to 6 carbon atoms while the group is substituted with 1 to 13 halogen atoms that may be the same with or different from each other. Examples thereof may include groups such as fluoromethyl, chloromethyl, bromomethyl, difluoromethyl, dichloromethyl, trifluoromethyl, trichloromethyl, chlorodifluoromethyl, bromodifluoromethyl, 2-fluoroethyl, 1-chloroethyl, 2-chloroethyl, 1-bromoethyl, 2-bromoethyl, 2,2-difluoroethyl, 2-chloro-2,2-difluoroethyl, 1,2-dichloroethyl, 2,2-dichloroethyl, 2,2,2-trifluoroethyl, 2,2,2-trichloroethyl, 1,1,2,2-tetrafluoroethyl, pentafluoroethyl, 2-bromo-2-chloroethyl, 2-chloro-1,1,2,2-tetrafluoroethyl, 1-chloro-1,2,2,2-tetrafluoroethyl, 1-chloropropyl, 2-chloropropyl, 3-chloropropyl, 2-bromopropyl, 3-bromopropyl, 2-bromo-1-methylethyl, 3-iodopropyl, 2,3-dichloropropyl, 2,3-dibromopropyl, 3,3,3-trifluoropropyl, 3,3,3-trichloropropyl, 3-bromo-3,3-difluoropropyl, 3,3-dichloro-3-fluoropropyl, 2,2,3,3-tetrafluoropropyl, 1-bromo-3,3,3-trifluoropropyl, 2,2,3,3,3-pentafluoropropyl, 2,2,2-trifluoro-1-trifluoromethylethyl, heptafluoropropyl, 1,2,2,2-tetrafluoro-1-trifluoromethylethyl, 2,3-dichloro-1,1,2,3,3-pentafluoropropyl, 1-fluoro-1-methylethyl, 1-methyl-2,2,2-trifluoroethyl, 2-chlorobutyl, 3-chlorobutyl, 4-chlorobutyl, 2-chloro-1,1-dimethylethyl, 4-bromobutyl, 3-bromo-2-methylpropyl, 2-bromo-1,1-dimethylethyl, 2,2-dichloro-1,1-dimethylethyl, 2-chloro-1-chloromethyl-2-methylethyl, 4,4,4-trifluorobutyl, 3,3,3-trifluoro-1-methylpropyl, 3,3,3-trifluoro-2-methylpropyl, 2,3,4-trichlorobutyl, 2,2,2-trichloro-1,1-dimethylethyl, 4-chloro-4,4-difluorobutyl, 4,4-dichloro-4-fluorobutyl, 4-bromo-4,4-difluorobutyl, 2,4-dibromo-4,4-difluorobutyl, 3,4-dichloro-3,4,4-trifluorobutyl, 3,3-dichloro-4,4,4-trifluorobutyl, 4-bromo-3,3,4,4-tetrafluorobutyl, 4-bromo-3-chloro-3,4,4-trifluorobutyl, 2,2,3,3,4,4-hexafluorobutyl, 2,2,3,4,4,4-hexafluorobutyl, 2,2,2-trifluoro-1-methyl-1-trifluoromethylethyl, 3,3,3-trifluoro-2-trifluoromethylpropyl, 2,2,3,3,4,4,4-heptafluorobutyl, 2,3,3,3-tetrafluoro-2-trifluoromethylpropyl, 1,1,2,2,3,3,4,4-octafluorobutyl, nonafluorobutyl, 4-chloro-1,1,2,2,3,3,4,4-octafluorobutyl, 5-fluoropentyl, 5-chloropentyl, 5,5-difluoropentyl, 5,5-dichloropentyl, 5,5,5-trifluoropentyl, 6,6,6-trifluorohexyl and 5,5,6,6,6-pentafluorohexyl.
    [0029] The C2-6 alkenyl group represents, unless otherwise particularly defined, a linear or branched chain alkenyl group having 2 to 6 carbon atoms. Examples thereof may include groups such as vinyl, 1-propenyl, isopropenyl, 2-propenyl, 1-butenyl, 1-methyl-1-propenyl, 2-butenyl, 1-methyl-2-propenyl, 3-butenyl, 2-methyl-1-propenyl, 2-methyl-2-propenyl, 1,3-butadienyl, 1-pentenyl, 1-ethyl-2-propenyl, 2-pentenyl, 1-methyl-1-butenyl, 3-pentenyl, 1-methyl-2-butenyl, 4-pentenyl, 1-methyl-3-butenyl, 3-methyl-1-butenyl, 1,2-dimethyl-2-propenyl, 1,1-dimethyl-2-propenyl, 2-methyl-2-butenyl, 3-methyl-2-butenyl, 1,2-dimethyl-1-propenyl, 2-methyl-3-butenyl, 3-methyl-3-butenyl, 1,3-pentadienyl, 1-vinyl-2-propenyl, 1-hexenyl, 1-propyl-2-propenyl, 2-hexenyl, 1-methyl-1-pentenyl, 1-ethyl-2-butenyl, 3-hexenyl, 4-hexenyl, 5-hexenyl, 1-methyl-4-pentenyl, 1-ethyl-3-butenyl, 1-(isobutyl)vinyl, 1-ethyl-1-methyl-2-propenyl, 1-ethyl-2-methyl-2-propenyl, 1-(isopropyl)-2-propenyl, 2-methyl-2-pentenyl, 3-methyl-3-pentenyl, 4-methyl-3-pentenyl, 1,3-dimethyl-2-butenyl, 1,1-dimethyl-3-butenyl, 3-methyl-4-pentenyl, 4-methyl-4-pentenyl, 1,2-dimethyl-3-butenyl, 1,3-dimethyl-3-butenyl, 1,1,2-trimethyl-2-propenyl, 1,5-hexadienyl, 1-vinyl-3-butenyl and 2,4-hexadienyl.
    [0030] The C3-8 cycloalkenyl group represents, unless otherwise particularly defined, a cyclic alkenyl group having 3 to 8 carbon atoms. Examples thereof may include groups such as 1-cyclopentenyl, 2-cyclopentenyl, 3-cyclopentenyl, 1-cyclohexenyl, 2-cyclohexenyl, 3-cyclohexenyl, 2-cycloheptenyl and 2-cyclooctenyl.
    [0031] The C2-6 alkynyl group represents, unless otherwise particularly defined, a linear or branched chain alkynyl group having 2 to 6 carbon atoms. Examples thereof may include groups such as ethynyl, 1-propynyl, 2-propynyl, 1-butynyl, 1-methyl-2-propynyl, 2-butynyl, 3-butynyl, 1-pentynyl, 1-ethyl-2-propynyl, 2-pentynyl, 3-pentynyl, 1-methyl-2-butynyl, 4-pentynyl, 1-methyl-3-butynyl, 2-methyl-3-butynyl, 1-hexynyl, 1-(n-propyl)-2-propynyl, 2-hexynyl, 1-ethyl-2-butynyl, 3-hexynyl, 1-methyl-2-pentynyl, 1-methyl-3-pentynyl, 4-methyl-1-pentynyl, 3-methyl-1-pentynyl, 5-hexynyl, 1-ethyl-3-butynyl, 1-ethyl-1-methyl-2-propynyl, 1-(isopropyl)-2-propynyl, 1,1-dimethyl-2-butynyl and 2,2-dimethyl-3-butynyl.
    [0032] The C1-10 alkoxy group represents, unless otherwise particularly defined, a (C1-10 alkyl)-O- group, where the alkyl moiety has the same meanings as defined above. Examples thereof may include groups such as methoxy, ethoxy, propoxy, n-propoxy, isopropoxy, butoxy, pentyloxy and hexyloxy.
    [0033] The C1-6 alkoxy C1-3 alkyl group represents, unless otherwise particularly defined, a (C1-6 alkyl)-O-(C1-3 alkyl) group, where the alkyl moiety has the same meaning as defined above. Examples may include groups such as methoxymethyl, ethoxymethyl, n-propoxymethyl, iso-propoxymethyl, n-butoxymethyl, iso-butoxymethyl, sec-butoxymethyl, n-pentyloxymethyl, 2-pentyloxymethyl, 3-pentyloxymethyl, n-hexyloxymethyl, 1-methoxyethyl, 1-ethoxyethyl, 1-methoxypropyl, 1-ethoxypropyl, 2-methoxyethyl, 2-ethoxyethyl, 3-methoxypropyl, 3-ethoxypropyl, 2-methoxypropyl, 2-ethoxypropyl, 2-methoxy-1-methylethyl and 2-ethoxy-1-methylethyl.
    [0034] The C1-6 haloalkoxy group represents, unless otherwise particularly defined, a (C1-6 alkyl)-O- group, where the alkyl moiety has the same meaning as defined above. The alkyl moiety represents a substituent substituted with 1 to 13 halogen atoms that may be the same with or different from each other. Examples of the group may include groups such as chloromethoxy, difluoromethoxy, chlorodifluoromethoxy, trifluoromethoxy, 2,2-difluoroethoxy and 2,2,2-trifluoroethoxy.
    [0035] The C3-8 cycloalkyloxy group represents, unless otherwise particularly defined, a (C3-8 cycloalkyl)-O- group, where the cycloalkyl moiety has the same meaning as defined above. Examples may include groups such as cyclopropyloxy, cyclobutyloxy, cyclopentyloxy and cyclohexyloxy.
    [0036] The C3-8 cycloalkyl C1-3 alkyloxy group represents, unless otherwise particularly defined, a (C3-8 cycloalkyl-C1-3 alkyl)-O- group, where the cycloalkylalkyl moiety has the same meanings as defined above. Examples may include groups such as cyclopropylmethoxy, 1-cyclopropylethoxy, 2-cyclopropylethoxy, 1-cyclopropylpropoxy, 2-cyclopropylpropoxy, 3-cyclopropylpropoxy, cyclobutylmethoxy, cyclopentylmethoxy and cyclohexylmethoxy.
    [0037] The C2-6 alkenyloxy group and the C2-6 alkynyloxy group represent, unless otherwise particularly defined, a (C2-6 alkenyl)-O- group and a (C2-6 alkynyl)-O- group, respectively, where the alkenyl moiety and the alkynyl moiety have the same meanings as defined above. Examples may include groups such as 2-propenyloxy and 2-propynyloxy.
    [0038] The C1-6 hydroxyalkyl group represents, unless otherwise particularly defined, a C1-6 alkyl group while one hydroxyl group is substituted. Examples may include groups such as hydroxymethyl, 1-hydroxyethyl, 1-hydroxypropyl, 1-hydroxy-1-methylethyl and 1-hydroxy-2-methylpropyl.
    [0039] The C1-6 alkylthio group, the C1-6 alkylsulfinyl group and the C1-6 alkylsulfonyl group represent, unless otherwise particularly defined, a (C1-6 alkyl)-S- group, a (C1-6 alkyl)-SO- group and a (C1-6 alkyl)-SO2- group, respectively, where the alkyl moiety has the same meaning as defined above. Examples thereof may include groups such as methylthio, ethylthio, n-propylthio, isopropylthio, methylsulfinyl, methylsulfonyl, ethylsulfonyl, n-propylsulfonyl and isopropylsulfonyl.
    [0040] The mono(C1-6 alkyl)amino group represents, unless otherwise particularly defined, a (C1-6 alkyl)-NH- group, where the alkyl moiety has the same meaning as defined above. Examples thereof may include groups such as methylamino, ethylamino, n-propylamino and isopropylamino.
    [0041] The di(C1-6 alkyl)amino group represents, unless otherwise particularly defined, a di(C1-6 alkyl)N- group where the alkyl moiety has the same meaning as defined above. Examples thereof may include groups such as dimethylamino, diethylamino, methylethylamino, dipropylamino and dibutylamino.
    [0042] The mono(C1-6 alkyl)aminocarbonyl group represents, unless otherwise particularly defined, a (C1-6 alkyl)-NHCO-group where the alkyl moiety has the same meaning as defined above. Examples thereof may include groups such as methylaminocarbonyl and ethylaminocarbonyl.
    [0043] The di(C1-6 alkyl) aminocarbonyl group represents, unless otherwise particularly defined, a di(C1-6 alkyl)NCO-group where the alkyl moiety has the same meaning as defined above. Examples thereof may include groups such as dimethylaminocarbonyl, diethylaminocarbonyl, methylethylaminocarbonyl, dipropylaminocarbonyl and dibutylaminocarbonyl.
    [0044] The mono(C1-6 alkyl) aminosulfonyl group represents, unless otherwise particularly defined, a (C1-6 alkyl)-NHSO2-group where the alkyl moiety has the same meaning as defined above. Examples thereof may include groups such as methylaminosulfonyl and ethylaminosulfonyl.
    [0045] The di(C1-6 alkyl)aminosulfonyl group represents, unless otherwise particularly defined, a di(C1-6 alkyl)NSO2-group where the alkyl moiety has the same meaning as defined above. Examples thereof may include groups such as dimethylaminosulfonyl, diethylaminosulfonyl, methylethylaminosulfonyl, dipropylaminosulfonyl and dibutylaminosulfonyl.
    [0046] The C1-6 alkoxycarbonyl group represents, unless otherwise particularly defined, a (C1-6 alkyl)-O(C=O)- group, where the alkyl moiety has the same meaning as defined above. Examples thereof may include groups such as methoxycarbonyl, ethoxycarbonyl, n-propoxycarbonyl, isopropoxycarbonyl and t-butoxycarbonyl.
    [0047] The C1-6 acyl group represents, unless otherwise particularly defined, a linear or branched chain aliphatic acyl group having 1 to 6 carbon atoms. Examples thereof may include groups such as formyl, acetyl, propionyl, isopropionyl, butyryl and pivaloyl.
    [0048] The C1-6 haloalkylthio group, the C1-6 haloalkylsulfinyl group and the C1-6 haloalkylsulfonyl group represent, unless otherwise particularly defined, a (C1-6 haloalkyl)-S- group, a (C1-6 haloalkyl)-SO- group and a (C1-6 haloalkyl)-SO2- group, respectively, where the haloalkyl moiety has the same meaning as defined above, respectively. Examples thereof may include groups such as difluoromethylthio, trifluoromethylthio, chloromethylsulfinyl, difluoromethylsulfinyl, trifluoromethylsulfinyl, chloromethylsulfonyl, difluoromethylsulfonyl and trifluoromethylsulfonyl.
    [0049] The C1-6 haloalkylcarbonyl group represents, unless otherwise particularly defined, a (C1-6 haloalkyl)-CO- group, where the haloalkyl moiety has the same meanings as defined above. Examples thereof may include groups such as chloroacetyl, trifluoroacetyl and pentafluoropropionyl.
    [0050] The tri(C1-6 alkyl) silyl group represents, unless otherwise particularly defined, a tri(C1-6 alkyl)silyl group, where the alkyl moiety has the same meanings as defined above. Examples thereof may include groups such as trimethylsilyl, triethylsilyl, tri(n-propyl)silyl, tri(n-butyl)silyl and tri(n-hexyl)silyl.
    [0051] The C1-6 alkoxyiminomethyl group represents, unless otherwise particularly defined, a (C1-6 alkyl)-O-N=CH- group, where the alkoxy moiety has the same meanings as defined above. Examples thereof may include groups such as methoxy-iminomethyl and ethoxyiminomethyl.
    [0052] The optionally substituted phenyl group represents, unless otherwise particularly defined, groups such as phenyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2-fluorophenyl, 3-fluorophenyl, 4-fluorophenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 2-methoxyphenyl, 3-methoxyphenyl, 4-methoxyphenyl, 2-nitrophenyl, 3-nitrophenyl and 4-nitrophenyl.
    [0053] The optionally substituted benzyloxy group represents, unless otherwise particularly defined, a (phenyl)-CH2-O-groups, where the phenyl moiety has the same meaning as defined above. Examples thereof may include groups such as benzyloxy, 2-chlorobenzyloxy, 3-chlorobenzyloxy, 4-chlorobenzyloxy, 2-fluorobenzyloxy, 3-fluorobenzyloxy, 4-fluorobenzyloxy, 2-methylbenzyloxy, 3-methylbenzyloxy, 4-methylbenzyloxy, 2-methoxybenzyloxy, 3-methoxybenzyloxy, 4-methoxybenzyloxy, 2-nitrobenzyloxy, 3-nitrobenzyloxy and 4-nitrobenzyloxy.
    [0054] The optionally substituted phenylthio group represents, unless otherwise particularly defined, a (phenyl)-S- groups, where the phenyl moiety has the same meaning as defined above. Examples thereof may include groups such as phenylthio, 2-chlorophenylthio, 3-chlorophenylthio, 4-chlorophenylthio, 2-fluorophenylthio, 3-fluorophenylthio, 4-fluorophenylthio, 2-methylphenylthio, 3-methylphenylthio, 4-methylphenylthio, 2-methoxyphenylthio, 3-methoxyphenylthio, 4-methoxyphenylthio, 2-nitrophenylthio, 3-nitrophenylthio and 4-nitrophenylthio.
    [0055] The optionally substituted benzylthio group represents, unless otherwise particularly defined, a (phenyl)-CH2-S-groups, where the phenyl moiety has the same meaning as defined above. Examples thereof may include groups such as benzylthio, 2-chlorobenzylthio, 3-chlorobenzylthio, 4-chlorobenzylthio, 2-fluorobenzylthio, 3-fluorobenzylthio, 4-fluorobenzylthio, 2-methylbenzylthio, 3-methylbenzylthio, 4-methylbenzylthio, 2-methoxybenzylthio, 3-methoxybenzylthio, 4-methoxybenzyloxy, 2-nitrobenzylthio, 3-nitrobenzylthio and 4-nitrobenzylthio.
    [0056] The term 'R1 and R2 may form a 5-membered or 6-membered ring with an atom arbitrarily selected from the group consisting of a carbon atom, an oxygen atom, a nitrogen atom and a sulfur atom, together with the nitrogen atom to which R1 and R2 are bonded' may include, unless otherwise particularly defined, a case of forming a ring such as pyrrolidine, pyrazolidine, oxazolidine, thiazolidine, imidazolidine, isoxazolidine, isothiazolidine, piperidine, piperazine, hexahydropyridazine, morpholine, or thiomorpholine.
    [0057] In regard to the term 'R1 and R2 may form a 5-membered or 6-membered ring (the 5-membered or 6-membered ring is independently substituted with 1 to 4 halogen atoms or/and a C1-6 haloalkyl group) with an atom arbitrarily selected from the group consisting of a carbon atom, an oxygen atom, a nitrogen atom and a sulfur atom, together with the nitrogen atom to which R1 and R2 are bonded', unless otherwise particularly defined, for example, 2-trifluoromethylpyrrolidin-1-yl, 3,3-difluoropyrrolidin-1-yl, 4-trifluoromethylpiperidin-1-yl, or 3,3,4,4-tetrafluoropyrrolidin-1-yl, may be mentioned.
    [0058] When for the compound of Formula [I] a hydroxyl group, a carboxyl group, an amino group, or the like is present in its structure, or alternatively when the nitrogen atom of the compound of Formula [I] where the nitrogen atom forms a pyrazole ring or a pyrimidine ring shows a basic property, the agriculturally acceptable salt refers to a salt of the compound with metal or organic base or a salt of the compound with mineral acid or organic acid. As the metal, there are alkali metals such as sodium and potassium; and alkaline-earth metals such as magnesium and calcium. As the organic base, there are triethylamine, diisopropylamine and the like. As the mineral acid, there are hydrochloric acid, sulfuric acid and the like. As the organic acid, there are acetic acid, methanesulfonic acid, p-toluenesulfonic acid and the like.
    [0059] In regard to the compound that can be included in the invention, there may be a case where a geometric isomer of E-form and Z-form exists according to the type of a substituent. The invention includes all of E-form, Z-form and a mixture including E-form and Z-form in an arbitrary proportion. Further, in regard to the compound that can be included in the invention, there exists an optically active substance caused by the presence of one or more asymmetric carbon atoms. The invention includes all of optically active substances as well as racemate. Moreover, when the compound that can be included in the invention has a hydroxyl group as a substituent, there may be a compound with a keto-enol isomer and the invention also includes the conformation thereof.
    [0060] Next, representative examples of the compound of the present application represented by Formula [1] will be shown in Tables 1 to 40. However, the compound of the present application is not limited to those compounds. For the compound Nos., refer to the descriptions below.
    [0061] The following abbreviations in Tables in the present specification represent groups as shown below, respectively. Me: methyl group Et: ethyl group n-Pr: n-propyl group iso-Pr: isopropyl group c-Pr: cyclopropyl group n-Bu: n-butyl group sec-Bu: sec-butyl group iso-Bu: iso-butyl group tert-Bu: tert-butyl group n-Pen: n-pentyl group 2-Pen: 2-pentyl group 3-Pen: 3-pentyl group c-Pen: cyclopentyl group c-Hex: cyclohexyl group
    [0062] In addition, the following abbreviations refer to corresponding meanings, respectively. 3-Cl: a chlorine atom is substituted at 3rd position 3-CF3-4-COOMe: a trifluoromethyl group is substituted at 3rd position and a methoxycarbonyl group is substituted at 4th position 3,5-(Me)2: methyl groups are substituted at 3rd and 5th positions, respectively
    [0063] [Table 1]
    [0064] [Table 2]Compound NoRR1 R2 XYm0046 iso-Pr tert-BuHCF3 -0047 iso-PrCH2CF3 HH-0048 iso-PrCH2CF3 HF-0049 iso-PrCH2CF3 HCl-0050 iso-PrCH2CF3 HBr-0051 iso-PrCH2CF3 HI-0052 iso-PrCH2CF3 HOH-0053 iso-PrCH2CF3 HOMe-0054 iso-PrCH2CF3 HOEt-0055 iso-PrCH2CF3 HOCH3 c-Pr-0056 iso-PrCH2CF3 HOCHF3 -0057 iso-PrCH2CF3 HOCF3 -0058 iso-PrCH2CF3 HOCH3CHF2 -0059 iso-PrCH2CF3 HOCH2CF3 -0060 iso-PrCH2CF3 HSMe-0061 iso-PrCH2CF3 HSOMe-0062 iso-PrCH2CF3 HSO2Me-0063 iso-PrCH2CF3 HSCF3 -0064 iso-PrCH2CF3 HSOCF3 -0065 iso-PrCH2CF3 HSO2CF3 -0066 iso-PrCH2CF3 HNH2 -0067 iso-PrCH2CF3 HHHMe-0068 iso-PrCH2CF3 HNHiso-Pr-0069 iso-PrCH2CF3 HN(Me)2 -0070 iso-PrCH2CF3 HN(Et)2 -0071 iso-PrCH2CF3 HCN-0072 iso-PrCH2CF3 HCHO-0073 iso-PrCH2CF3 HCOMe-0074 iso-PrCH2CF3 HCOEt-0075 iso-PrCH2CF3 HCO2H-0076 iso-PrCH2CF3 HCO2Me - 0077 iso-PrCH2CF3 HCO2Et-0078 iso-PrCH2CF3 HCONH2 -0079 iso-PrCH2CF3 HCONHMe-0080 iso-PrCH2CF3 HCON(Me)2 -0081 iso-PrCH2CF3 HMe-0082 iso-PrCH2CF3 HEt-0083 iso-PrCH2CF3 H iso-Pr 0084 iso-PrCH2CF3 H c-Pr-0085 iso-PrCH2CF3 HCH2F-0086 iso-PrH2CF3 11HCH2Cl-0087 iso-PrCH3CF3 HCH2Br-0088 iso-PrCH2CF3 HCHF3 -0089 iso-PrCH2CF3 HCF3 -0090 iso-PrCH(Me)CF3 HH-0091 iso-PrCH(Me)CF3 HF-0092 iso-PrCH(Me)CF3 HCl-0093 iso-PrCH(Me)CF3 HBr-0094 iso-PrCH(Me)CF3 HI-0095 iso-PrCH(Me)CF3 HOH-0096 iso-PrCH(Me)CF3 HOMe-
    [0065] [Table 3]Compound NoRR1 R1 XYm0097 iso-PrCH(Me)CF3 HOEt-0098 iso-PrCH(Me)CF3 H0CH2 c-Pr-0099 iso-PrCH(Me)CF3 HOCHF3 -0100 iso-PrCH(Me)CF3 HOCF3 -0101 iso-PrCH(Me)CF3 HOCH2CHF2 -0102 iso-PrCH(Me)CF3 HOCH2CF3 -0103 iso-PrCH(Me)CF3 HSMe-0104 iso-PrCH(Me)CF3 HSOMe-0105 iso-PrCH(Me)CF3 HSO2Me-0106 iso-PrCH(Me)CF3 HSCF3 -0107 iso-PrCH(Me)CF3 HSOCF3 -0108 iso-PrCH(Me)CF3 HSO2CF3 -0109 iso-PrCH(Me)CF3 HNH3 -0110 iso-PrCH(Me)CF3 HNHMe-0111 iso-PrCH(Me)CF3 HNHiso-Pr-0112 iso-PrCH(Me)CF3 HN(Me)2 0113 iso-PrCH(Me)CF3 HN(Et)2 -0114 iso-PrCH(Me)CF3 HCN-0115 iso-PrCH(Me)CF3 HCHO-0116 iso-PrCH(Me)CF3 HCOMe-0117 iso-PrCH(Me)CF3 HCOEt-0118 iso-PrCH(Me)CF3 HCO2H-0119 iso-PrCH(Me)CF3 HCO2Me 0120 iso-PrCH(Me)CF3 HCO2Et-0121 iso-PrCH(Me)CF3 HCONH2 -0122 iso-PrCH(Me)CF3 HCOMHMe-0123 iso-PrCH(Me)CF3 HCON(Me)2 -0124 iso-PrCH(Me)CF3 HMe-0125 iso-PrCH(Me)CF3 HEt-0126 iso-PrCH(Me)CF3 H iso-Pr 0127 iso-PrCH(Me)CF3 H c-Pr-0128 iso-PrCH(Me)OF3 HCH2F-0129 iso-PrCH(Me)CF3 HCH2Cl-0130 iso-PrCH(Me)CF3 HCH2Br-0131 iso-PrCH(Me)CF3 HCHF2 -0132 iso-PrCH(Me)CF3 HCF3 -0133 iso-PrEtEtH-0134 iso-PrEtEtF-0135 iso-PrEtEtCl-0136 iso-PrEtEtBr-0137 iso-PrEtEtCN-0138 iso-PrEtEtMe-0139 iso-PrEtEtCF3 -0140 iso-Pr-CH(CF3)CH2)3-H-0141 iso-Pr-CH(CF3)CH2)3- -0142 iso-Pr-CH(CF3)CH2)3-Cl-0143 iso-Pr-CH(CF3)CH2)3-Br-0144 iso-Pr-CH(CF3)CH2)3-CN-0145 iso-Pr-CH(CF3)CH2)3-Me-0146 iso-Pr-CH(CF3)CH2)3-CF3 -
    [0066] [Table 4]Compound NoRR1 R2 XYm0147 iso-Pr-(CH2)3CH(Me)(CH2)3-H-0148 iso-Pr-(CH2)3CH(Me)(CH2)3-F-0149 iso-Pr-(CH2)3CH(Me)(CH2)3-Cl-0150 iso-Pr-(CH2)3CH(Me)(CH2)3-Br-0151 iso-Pr-(CH2)3CH(Me)(CH2)3-CN-0152 iso-Pr-(CH2)3CH(Me)(CH2)3-Me-0153 iso-Pr-(CH2)3CH(Me)(CH2)3-CF3 -0154 n-Fr iso-PrHH-0155 n-Pr iso-PrHCl-0156 n-Pr iso-PrHCN-0157 n-Pr iso-PrHMe-0158 n-PrCH2CF3 HH-0159 n-PrCH2CF3 HCl-0160 n-PrCH2CF3 HCN-0161 n-PrCH2CF3 HMe-0162 n-PrEtEtH-0163 n-PrEtEtCl-0164 n-PrEtEtCN-0165 n-PrEtEtMe-0166 n-Pr-(CH2)3CH(Me)(CH2)3-H-0167 n-Pr-(CH2)3CH(Me)(CH2)3-Cl-0168 n-Pr-(CH2)3CH(Me)(CH2)3-CN-0169 n-Pr-(CH2)3CH(Me)(CH2)3-Me-0170 n-Bu iso-PrHH-0171 n-Bu iso-PrHCl-0172 n-Bu iso-PrHCN-0173 n-Bu iso-PrHMe-0174 n-BuCH2CF3 HH-0175 n-BuCH2CF3 HCl-0176 n-BuCH2CF3 HCN-0177 n-BuCH2CF3 HMe-0178 n-BuEtEtH-0179 n-BuEtEtCl-0180 n-BuEtEtCN-0181 n-BuEtEtMe-0182 n-Bu-(CH2)3CH(Me)(CH2)3-H-0183 n-Bu-(CH2)3CH(Me)(CH2)3-Cl-0184 n-Bu-(CH2)3CH(Me)(CH2)3-CN-0185 n-Bu-(CH2)3CH(Me)(CH2)3-Me-0186 sec-BuHHH-0187 sec-BuHHCl-0188 sec-BuHHCN-0189 sec-BuHHMe-0190 sec-BuMeHH-0191 sec-BuMeHCl-0192 sec-BuMeHCN-0193 sec-BuMeHMe-0194 sec-BuEtHH-0195 sec-BuEtHCl-0196 sec-BuEtHCN-0197 sec-BuEtHMe-
    [0067] [Table 5]Compound NoRR1 R2 XYm0198 sec-Bu iso-PrHH-0199 sec-Bu iso-PrHF-0200 sec-Bu iso-PrHa-0201 sec-Bu iso-PrHBr-0202 sec-Bu iso-PrHI-0203 sec-Bu iso-PrHOH-0204 sec-Bu iso-PrHOMe-0205 sec-Bu iso-PrHOEt-0206 sec-Bu iso-PrHOCH3 c-Pr-0307 sec-Bu iso-PrHOCHF3 -0208 sec-Bu iso-PrHOCF3 -0209 sec-Bu iso-PrHOCH3CF2 -0210 sec-Bu iso-PrHOCH2CF3 -0211 sec-Bu iso-PrHSMe-0212 sec-Bu iso-PrHSOMe-0213 sec-Bu iso-PrHSO2Me-0214 sec-Bu iso-PrHSCF3 -0215 sec-Bu iso-PrHSOCF3 -0216 sec-Bu iso-PrHSO2CF3 -0217 sec-Bu iso-PrHNH3 -0218 sec-Bu iso-PrHNHMe-0219 sec-Bu iso-PrHNHiso-Pr-0220 sec-Bu iso-PrHN(Me)2 -0221 sec-Bu iso-PrHN(Et)3 -0222 sec-Bu iso-PrHCN-0223 sec-Bu iso-PrHCHO-0224 sec-Bu iso-PrHCOMe-0225 sec-Bu iso-PrHCOEt-0226 sec-Bu iso-PrHCO2H-0227 sec-Bu iso-PrHCOMe - 0228 sec-Bu iso-PrHCO3Et-0229 sec-Bu iso-PrHCONH3 -0230 sec-Bu iso-PrHCONHMe-0231 sec-Bu iso-PrHCON(Me)2 -0232 sec-Bu iso-PrHMe-0233 sec-Bu iso-PrHEt-0234 sec-Bu iso-PrH iso-Pr-0235 sec-Bu iso-PrH c-Pr-0236 sec-Bu iso-PrHCH2F-0237 sec-Bu iso-PrHCH2Cl-0238 sec-Bu iso-PrHCH3Br-0239 sec-Bu iso-PrHCHF3 -0240 sec-Bu iso-PrHCF3 -0241 sec-Bu n-PrHH-0242 sec-Bu n-PrHCl-0243 sec-Bu n-PrHCN-0244 sec-Bu n-PrHMe-0245 sec-Bu n-BuHH-0246 sec-Bu n-BuHCl-0247 sec-Bu n-BuHCN-0248 sec-Bu n-BuHMe-
    [0068] [Table 6]Compound NoRR1 R2 XYm0249 sec-Bu iso-BuHH-0250 sec-Bu iso-BuHCl-0251 sec-Bu iso-BuHCN-0252 sec-Bu iso-BuHMe-0253 sec-Bu sec-BuHH-0254 sec-Bu sec-BuHa-0255 sec-Bu sec-BuHCN-0256 sec-Bu sec-BuHMe-0257 sec-Bu tert-BuHH-0258 sec-Bu tert-BuHF-0259 sec-Bu tert-BuHCl-0260 sec-Bu tert-BuHBr-0261 sec-Bu tert-BuHI-0262 sec-Bu tert-BuHOH-0263 sec-Bu tert-BuHOMe-0264 sec-Bu tert-BuHOEt-0265 sec-Bu tert-BuHOCH2 c-Pr-0266 sec-Bu tert-BuHOCHF2 -0267 sec-Bu tert-BuHOCF3 -0268 sec-Bu tert-BuHOCH2CHF3 -0269 sec-Bu tert-BuHOCH2CF3 -0270 sec-Bu tert-BuHSMe-0271 sec-Bu tert-BuHSOMe-0272 sec-Bu tert-BuHSO2Me-0273 sec-Bu tert-BuHSCF3 -0274 sec-Bu tert-BuHSOCF3 -0275 sec-Bu tert-BuHSOCF3 -0276 sec-Bu tert-BuHNH2 -0277 sec-Bu tert-BuHNHMe-0278 sec-Bu tert-BuHNHiso-Pr-0279 sec-Bu tert-BuHN(Me)2 -0280 sec-Bu tert-BuHN(Et)2 -0281 sec-Bu tert-BuHCN-0282 sec-Bu tert-BuHCHO-0283 sec-Bu tert-BuHCOMe-0284 sec-Bu tert-BuHCOEt-0285 sec-Bu tert-BuHCO3H-0286 sec-Bu tert-BuHCO2Me - 0287 sec-Bu tert-BuHCO3Et-0288 sec-Bu tert-BuHCONH3 -0289 sec-Bu tert-BuHCONHMe-0290 sec-Bu tert-BuHOON(Me)2 -0291 sec-Bu tert-BuHMe-0292 sec-Bu tert-BuHEt-0293 sec-Bu tert-BuH iso-Pr-0294 sec-Bu tert-BuH c-Pr-0295 sec-Bu tert-BuHCH3F-0296 sec-Bu tert-BuHCH2Cl-0297 sec-Bu tert-BuHCH3Br-0298 sec-Bu tert-BuHCHF2 -0299 sec-Bu tert-BuHCF3 -
    [0069] [Table 7]Compound NoRR1 R2 XYm0300 sec-Bu n-PenHH-0301 sec-Bu n-PenHCl-0302 sec-Bu n-PenHCN-0303 sec-Bu n-PenHMe-0304 sec-BuCH(Me)n-PrHH-0305 sec-BuCH(Me)n-PrHCl-0306 sec-BuCH(Me)n-PrHCN-0307 sec-BuCH(Me)n-PrHMe-0308 sec-BuCH(Et)2 HH-0309 sec-BuCH(Et)2 HCl-0310 sec-BuCH(Et)2 HCN-0311 sec-BuCH(Et)2 HMe-0312 sec-BuCH(Me)CH(Me)2 HH-0313 sec-BuCH(Me)CH(Me)2 HCl-0314 sec-BuCH(Me)CH(Me)2 HCN-0315 sec-BuCH(Me)CH(Me)2 HMe-0316 sec-BuCH2C(Me)3 HH-0317 sec-BuCH2C(Me)3 HCl-0318 sec-BuCH2C(Me)3 HCN-0319 sec-BuCH2C(Me)3 HMe-0320 sec-BuCH(Me)C(Me)3 HH-0321 sec-BuCH(Me)C(Me)3 HCl-0322 sec-BuCH(Me)C(Me)3 HCN-0323 sec-BuCH(Me)C(Me)3 HMe-0324 sec-Bu n-HexHH-0325 sec-Bu n-HexHCl-0326 sec-Bu n-HexHCN-0327 sec-Bu n-HexHMe-0328 sec-Bu c-PrHH-0329 sec-Bu c-PrHCl-0330 sec-Bu c-PrHCN-0331 sec-Bu c-PrHMe-0332 sec-Bu c-PenHH-0333 sec-Bu c-PenHCl-0334 sec-Bu c-PenHCN-0335 sec-Bu c-PenHMe-0336 sec-Bu c-HexHH-0337 sec-Bu c-HexHCl-0338 sec-Bu c-HexHCN-0339 sec-Bu c-HexHMe-0340 sec-BuCH2CHF3 HH-0341 sec-BuCH2CHF3 HCl-0342 sec-BuCH2CHF3 HCN-0343 sec-BuCH2CHF3 HMe-0344 sec-BuCH2CClF3 HH-0345 sec-BuCH2CClF3 HCl-0346 sec-BuCH2CClF3 HCN-0347 sec-BuCH2CClF3 HMe-0348 sec-BuCH2CF3 HH-0349 sec-BuCH2CF3 HF-0350 sec-BuCH2CF3 HCl-
    [0070] [Table 8]Compound NoRR1 R2 XYm0351 sec-BuCH2CF3 HBr-0352 sec-BuCH2CF3 HI-0353 sec-BuCH2CF3 HOH-0354 sec-BuCH2CF3 HOMe-0355 sec-BuCH2CF3 HOEt-0356 sec-BuCH2CF3 HOCH3 c-Pr-0357 sec-BuCH2CF3 HOCH2Ph-0358 sec-BuCH2CF3 HOCHF3 -0359 sec-BuCH2CF3 HOCH2CHF2 -0360 sec-BuCH2CF3 HOCH2CF3 -0361 sec-BuCH2CF3 HSMe-0362 sec-BuCH2CF3 HSOMe-0363 sec-BuCH2CF3 HSO3Me-0364 sec-BuCH2CF3 HSCF3 -0365 sec-BuCH2CF3 HOOCF3 -0366 sec-BuCH2CF3 HSO2CF3 -0367 sec-BuCH2CF3 HNH2 -0368 sec-BuCH2CF3 HNHMe - 0369 sec-BuCH2CF3 HNHiso-Pr-0370 sec-BuCH2CF3 HN(Me)2 -0371 sec-BuCH2CF3 HN(Et)2 -0372 sec-BuCH2CF3 HCN-0373 sec-BuCH2CF3 HCHO-0374 sec-BuCH2CF3 HCOMe-0375 sec-BuCH2CF3 HCOEt-0376 sec-BuCH2CF3 HCO3H-0377 sec-BuCH2CF3 HCO3ME - 0378 sec-BuCH2CF3 HCO3Et-0319 sec-BuCH2CF3 HOONH2 -0380 sec-BuCH2CF3 HCONHMe-0381 sec-BuCH2CF3 HCON(Me)2 -0382 sec-BuCH2CF3 HCH=NOH-0383 sec-BuCH2CF3 HCH=NOMe-0384 sec-BuCH2CF3 HMe-0385 sec-BuCH2CF3 HEt-0386 sec-BuCH2CF3 H iso-Pr-0387 sec-BuCH2CF3 H c-Pr-0388 sec-BuCH2CF3 HCH3F-0389 sec-BuCH2CF3 HCH3Cl-0390 sec-BuCH2CF3 HCH2Br-0391 sec-BuCH2CF3 HCHF2 -0392 sec-BuCH2CF3 HCF3 -0393 sec-BuCH2CF3 HCH3OH-0334 sec-BuCH2CF3 HCH(OH)Me-0396 sec-BuCH2CF3 HCH3Me-0396 sec-BuCH2CF3 HCH(OMe)Me-0397 sec-BuCH2CF3 HCl3-F0398 sec-BuCH2CF3 HCl3-Cl0399 sec-BuCH2CF3 HCl3-Br0400 sec-BuCH2CF3 HCl3-I0401 sec-BuCH2CF3 HCl3-Me
    [0071] [Table 9]Compound NoRR1 R2 XYm0402 sec-BuCH2CF3 HCl3-Et0403 sec-BuCH2CF3 HCl3-iso-Pr0404 sec-BuCH2CF3 HCl3-c-Pr0405 sec-BuCH2CF3 HCl3-C≡CH0406 sec-BuCH2CF3 HCl3-CH3OH0407 sec-BuCH2CF3 HCl3-CH3OMe0408 sec-BuCH2CF3 HCl3-CH2Cl0409 sec-BuCH2CF3 HCl3-CHF2 0410 sec-BuCH2CF3 HCl3-CF3 0411 sec-BuCH2CF3 HCl3-OH0412 sec-BuCH2CF3 HCl3-OMe0413 sec-BuCH2CF3 Ha3-OCHF2 0414 sec-BuCH2CF3 HCl3-SH0415 sec-BuCH2CF3 HCl3-SMe0416 sec-BuCH2CF3 HCl3-SOMe0417 sec-BuCH2CF3 HCl3-SO3Me0418 sec-BuCH2CF3 HCl3-SCF3 0419 sec-BuCH2CF3 HCl3-SOCF3 0420 sec-BuCH2CF3 HCl3-SO3CF3 0421 sec-BuCH2CF3 HCl3-NO2 0422 sec-BuCH2CF3 HCl3-NH2 0423 sec-BuCH2CF3 HCl3-NHMe0424 sec-BuCH2CF3 HCl3-N(Me)2 0425 sec-BuCH2CF3 HCl3-CN0426 sec-BuCH2CF3 HCl3-CHO0427 sec-BuCH2CF3 HCl3-OOMe0428 sec-BuCH2CF3 HCl3-CO3H0429 sec-BuCH2CF3 HCl3-CO3Et0430 sec-BuCH2CF3 HCl3-CONH3 0431 sec-BuCH2CF3 HCl3-CONHMe0432 sec-BuCH2CF3 HCl3-CON(Me)3 0433 sec-BuCH2CF3 HCl4-F0434 sec-BuCH2CF3 HCl4-Cl0435 sec-BuCH2CF3 HCl4-Br0436 sec-BuCH2CF3 HCl4-I0437 sec-BuCH2CF3 HCl4-Me0438 sec-BuCH2CF3 HCl4-CH3OH0439 sec-BuCH2CF3 HCl4-CH3OMe0440 sec-BuCH2CF3 HCl4-CH3Cl0441 sec-BuCH2CF3 HCl4-CHF3 0442 sec-BuCH2CF3 HCl4-CF3 0443 sec-BuCH2CF3 HCl4-OH0444 sec-BuCH2CF3 HCl4-Me0445 sec-BuCH2CF3 HCl4-OCHF3 0446 sec-BuCH2CF3 HCl4-SH0447 sec-BuCH2CF3 HCl4-SMe0448 sec-BuCH2CF3 HCl4-SOMe0449 sec-BuCH2CF3 HCl4-SO3Me0450 sec-BuCH2CF3 HCl4-SCF3 0451 sec-BuCH2CF3 HCl4-SOCF3 0452 sec-BuCH2CF3 HCl4-SO2CF3
    [0072] [Table 10]Compound NoRR1 R3 XYm0453 sec-BuCH3CF3 HCl4-SCN0454 sec-BuCH3CF3 HCl4-NO3 0455 sec-BuCH3CF3 HCl4-NH3 0456 sec-BuCH3CF3 HCl4-NHMe0457 sec-BuCH3CF3 HCl4-N(Me)3 0458 sec-BuCH3CF3 HCl4-CN0459 sec-BuCH3CF3 HCl4-CHO0460 sec-BuCH3CF3 HCl4-COMe0461 sec-BuCH3CF3 HCl4-CO3H0462 sec-BuCH3CF3 HCl4-CO3Et0463 sec-BuCH3CF3 HCl4-CONH3 0464 sec-BuCH3CF3 HCl4-CONHMe0465 sec-BuCH3CF3 HCl4-CON(Me)3 0466 sec-BuCH3CF3 HCl5-Cl0467 sec-BuCH3CF3 HCl5-Me0468 sec-BuCH3CF3 HCl5-CF3 0469 sec-BuCH3CF3 HCl5-OH0470 sec-BuCH3CF3 HCl5-OMe0471 sec-BuCH3CF3 HCl5-OCHF2 0472 sec-BuCH3CF3 HCl5-NH2 0473 sec-BuCH3CF3 HCl3-Me-4-F0474 sec-BuCH3CF3 HCl3-Me-4-Cl0475 sec-BuCH3CF3 HCl3,4-(Me)3 0476 sec-BuCH3CF3 HCl3-Me-4-OH0477 sec-BuCH3CF3 HCl3-Me-4-OMe0478 sec-BuCH3CF3 HCl3-Me-4-OCHF3,0479 sec-BuCH3CF3 HCl3-Et-4-Cl0480 sec-BuCH3CF3 HCl3-Et-4-OH0481 sec-BuCH3CF3 HCl3-iso-Pr-4-Cl0482 sec-BuCH3CF3 HCl3-iso-Pr-4-OH0483 sec-BuCH2CH3 HCl3-c-Pr-4-Cl0484 sec-BuCH2CH3 HCl3-c-Pr-4-OH0485 sec-BuCH3CH3 HCl3-Me-4-CN0486 sec-BuCH3CH3 HCl3-Et-4-CN0487 sec-BuCH2CH3 HCl3-c-Pr-4-CN0488 sec-BuCH2CH3 HCl3-GF3-4-Cl0489 sec-BuCH3CH3 HCl3-CF3-4-CO2Et0490 sec-BuCH3CH3 HCl3-CF3-4-CO2H0491 sec-BuCH3CH3 HCl3-CF3-4-NH2 0492 sec-BuCH3CH3 HCl3-CF3-4-CONH3 0493 sec-BuCH3CH3 HCl3-GF3-4-CONHMe0494 sec-BuCH3CH3 HCl3-CF3-4-CON(Me)2 0495 sec-BuCH3CH3 HCl3-CF3-4-Me0496 sec-BuCH3CH3 HCl3-CF3-4-Cl0497 sec-BuCH3CH3 HCl3-CF3-4-CN0498 sec-BuCH3CH3 HCl3-CF3-4-CO3Me0499 sec-BuCH3CH3 HCl3-CF3-4-CO3H0500 sec-BuCH2CH3 HCl3-CF3-4-CONH2 0501 sec-BuCH3CH3 HCl3-GF3-4-CONHMe0503 sec-BuCH3CH3 HCl3-CF3-4-CON(Me)2 0503 sec-BuCH3CH3 HCl3-CF3-4-NH2
    [0073] [Table 11]Compound NoRR1 R2 XYm0504 sec-BuCH2OF3 HCl3-NH3-4-Br0505 sec-BuCH2CF3 HCl3-NH3-4-Cl0506 sec-BuCH2CF3 HCl3NH2-4-F0507 sec-BuCH2CF3 HCl3-Cl-4-Br0508 sec-BuCH2CF3 HCl3,4-Br3 0509 sec-BuCH2CF3 HCl3,4-Cl2 0510 sec-BuCH2CF3 HCl3-NH3-4-CO3Et0511 sec-BuCH2CF3 HCl3-Cl-4-CO3Et0512 sec-BuCH2CF3 HCl3-NH3-4-CO3H0513 sec-BuCH2CF3 HCl3-Cl-4-CO3H0514 sec-BuCH2CF3 HCl3,4-(NH2)2 0515 sec-BuCH2CF3 HCl3-Cl-4-NH2 0516 sec-BuCH2CF3 HCl3-NH2-4-CONH3 0517 sec-BuCH2CF3 HCl3-Cl-4-CONH3 0518 sec-BuCH2CF3 HCl3-NH2-4-CONHMe0519 sec-BuCH2CF3 HCl3-Cl-4-CONHMe0520 sec-BuCH2CF3 HCl3-NH2-4-CON(Me)3 0521 sec-BuCH2CF3 HCl3-Cl-4-CON(Me)3 0522 sec-BuCH2CF3 HCl3-CO3Et-4-Cl0523 sec-BuCH2CF3 HCl3-CO3H-4-Cl0524 sec-BuCH2CF3 HCl3-CONH3-4-Cl0525 sec-BuCH2CF3 HCl3-CONHMe-4-Cl0526 sec-BuCH2CF3 HCl3-CON(Me)3-4-Cl0697 sec-BuCH2CF3 HCl3-CN-4-Cl0528 sec-BuCH2CF3 HCl3-NH3-4-CN0529 sec-BuCH2CF3 HCl3-Cl-4-CN0530 sec-BuCH2CF3 HCl3-CN-4-CN0531 sec-BuCH2CF3 HCl3-SMe-4-CN0532 sec-BuCH2CF3 HCl3-SOMe-4-CN0533 sec-BuCH2CF3 HCl3-SO3Me-4-CN0534 sec-BuCH2CF3 HCl3-SH-4-CN0535 sec-BuCH2CF3 HCl3-SCF3-4-CN0536 sec-BuCH2CF3 HCl3,5-(Me)2 0537 sec-BuCH2CF3 HCl3-Me-5-OH0538 sec-BuCH2CF3 HCl3-Me-5-OMe0539 sec-BuCH2CF3 HCl3-Me-5-OCHF2 0540 sec-BuCH2CF3 HCl3-OH-5-Me0541 sec-BuCH2CF3 HCl3-OMe-5-Me0542 sec-BuCH2CF3 HCl3-OCHF2-5-Me0543 sec-BuCH2CF3 HCl3-Et-5-OH0544 sec-BuCH2CF3 HCl3-c-Pr-5-OH0545 sec-BuCH2CF3 HCl3-OH-5-Et0546 sec-BuCH2CF3 HCl3-OH-5-c-Pr0547 sec-BuCH2CF3 HCl3-Me-5-NH2 0548 sec-BuCH2CF3 HCl3-Me-5-CO2Et0549 sec-BuCH2CF3 HCl3-Et-5-CO2Et0550 sec-BuCH2CF3 HCl3-Me-5-Cl0551 sec-BuCH2CF3 HCl3-Et-5-NH2 0552 sec-BuCH2CF3 HCl3-Et-5-Cl0553 sec-BuCH3CF3 HCl3-c-Pr-5-NH2 0554 sec-BuCH3CF3 HCl3-c-Pr-5-Cl
    [0074] [Table 12]Compound NoRR1 R2 XYm0555 sec-BuCH3CF3 HCl3-CF3-5-OH0556 sec-BuCH3CF3 HCl3-CF3-5-OMe0557 sec-BuCH3CF3 HCl3-CF3-5-OCHF3 0558 sec-BuCH3CF3 HCl3-CF3-5-NH3 0559 sec-BuCH3CF3 HCl3-CO3Et-5-OH0560 sec-BuCH3CF3 HCl3-CO3Et-5-OMe0561 sec-BuCH3CF3 HCl3-CO3Et-5-NH3 0562 sec-BuCH3CF3 HCl3-CO4Et-5-Cl0563 sec-BuCH3CF3 HCl3-CO2H-5-NH3 0564 sec-BuCH3CF3 HCl3-CO3H-5-Cl0565 sec-BuCH3CF3 HCl3-CONH2-5-NH3 0566 sec-BuCH3CF3 HCl3-CONH3-5-Cl0567 sec-BuCH3CF3 HCl3-CONHMe-5-NH3 0568 sec-BuCH3CF3 HCl3-CONHMe-5-Cl0569 sec-BuCH3CF3 HCl3-CON(Me)2-5-NH3 0570 sec-BuCH3CF3 HCl3-CON(Me)2-5-Cl0571 sec-BuCH3CF3 HCl3-CN-5-NH2 0572 sec-BuCH3CF3 HCl3-CN-5-Cl0573 sec-BuCH3CF3 HCl3,5-(NH3)3 0574 sec-BuCH3CF3 HCl3-CF3-5-SH0575 sec-BuCH3CF3 HCl3-CF3-5-SMe0576 sec-BuCH3CF3 HCl3-SMe-5-NH3 0577 sec-BuCH3CF3 HCl3-SOMe-5-NH3 0578 sec-BuCH3CF3 HCl3-SO3Me-5-NH3 0579 sec-BuCH3CF3 HCl3-SMe-5-Cl0580 sec-BuCH3CF3 HCl3-SOMe-5-Cl0581 sec-BuCH3CF3 HCl3-SO3Me-6-Cl0582 sec-BuCH3CF3 HCl4-Me-5-OH0583 sec-BuCH3CF3 HCl4-Me-5-OMe0584 sec-BuCH3CF3 HCl4-Me-5-OCHF3 0585 sec-BuCH3CF3 HCl4-Et-5-OH0586 sec-BuCH3CF3 HCl4-c-Pr-5-OH0587 sec-BuCH3CF3 HCl4-CO3Et-5-Me0588 sec-BuCH3CF3 HCl4-CO3H-5-Me0589 sec-BuCH3CF3 HCl4-NH3-5-Me0690 sec-BuCH3CF3 HCl4-Cl-5-Me0591 sec-BuCH3CF3 HCl4-CONH3-5-Me0592 sec-BuCH3CF3 HCl4-CONHMe-5-Me0593 sec-BuCH3CF3 HCl4-CON(Me)3-5-Me0594 sec-BuCH3CF3 HCl4-CO3-Et-5-CF3 0595 sec-BuCH3CF3 HCl4-CO3-H-5-CF3 0596 sec-BuCH3CF3 HCl4-Cl-5-CF3 0597 sec-BuCH3CF3 HCl4-NH3-5-CF3 0598 sec-BuCH3CF3 HCl4-CONH3-5-CF3 0599 sec-BuCH3CF3 HCl4-CONHMe-5-CF3 0600 sec-BuCH3CF3 HCl4-CONMe3-5-CF3 0601 sec-BuCH3CF3 HCl4-CO3Et-5-NH3 0602 sec-BuCH3CF3 HCl4-CO3Et-5-Cl0603 sec-BuCH3CF3 HCl4-CO3H-5-NH3 0604 sec-BuCH3CF3 HCl4-CO3H-5-Cl0605 sec-BuCH3CF3 HCl4-CONH3-5-NH3
    [0075] [Table 13]Componund NoRR1 R3 XYm0606 sec-BuCH2CF3 HCl4-CONH3-5-Cl0607 sec-BuCH2CF3 HCl4-CONHMe-5-NH3 0608 sec-BuCH3CF3 HCl4-CONHMe-5-Cl0609 sec-BuCH3CF3 HCl4-CON(Me)3-5-NH3 0610 sec-BuCH2CF3 HCl4-CON(Me)3-5-Cl0611 sec-BuCH3CF3 HCl4-F-5-NH3 0612 sec-BuCH3CF3 HCl4-Cl-5-NH3 0613 sec-BuCH3CF3 HCl4,5-Cl3 0614 sec-BuCH3CF3 HCl4-CN-5-NH2 0615 sec-BuCH3CF3 HCl4-CN-5-Cl0616 sec-BuCH3CF3 HCl4-CHO-5-NH3 0617 sec-BuCH3CF3 HCl4-CHO-5-Cl0618 sec-BuCH3CF3 HCl4-CHF3-5-NH2 0619 sec-BuCH3CF3 HCl4-CHF3-5-Cl0620 sec-BuCH2CF3 HCl4-CH3OH-5-NH3 0621 sec-BuCH3CF3 HCl4-CH3OH-5-Cl0622 sec-BuCH3CF3 HCl4-CH3-Cl-5-NH3 0623 sec-BuCH3CF3 HCl4-CH3-Cl-5-Cl0624 sec-BuCH3CF3 HCl4-CH3OMe-5-NH3 0625 sec-BuCH3CF3 HCl4-CH3OMe-5-Cl0626 sec-BuCH3CF3 HCl4-NO3-5-NH3 0627 sec-BuCH3CF3 HCl4-NO3-5-Cl0628 sec-BuCH3CF3 HCl4-SCN-5-NH3 0629 sec-BuCH3CF3 HCl4-SCN-5-Cl0630 sec-BuCH3CF3 HCl4-SH-5-NH3 0631 sec-BuCH3CF3 HCl4-SH-5-Cl0632 sec-BuCH3CF3 HCl4-SMe-5-NH2 0633 sec-BuCH3CF3 HCl4-SMe-5-Cl0634 sec-BuCH3CF3 HCl4-SCF3-5-NH3 0635 sec-BuCH3CF3 HCl4-SCF3-5-Cl0636 sec-BuCH3CF3 HCl3-Me-4-Cl-5-NH3 0637 sec-BuCH3CF3 HCl3-Me-4-F-5-NH3 0638 sec-BuCH3CF3 HCl3-Me-4-Cl-5-Cl0639 sec-BuCH3CF3 HCl3-Et-4-Cl-5-NH3 0640 sec-BuCH3CF3 HCl3-Et-4-Cl-5-Cl0641 sec-BuCH3CF3 HCl3-c-Pr-4-Cl-5-NH2 0642 sec-BuCH3CF3 HCl3-c-Pr-4-Cl-5-Cl0643 sec-BuCH3CF3 HCl3-Me-4-CHO-5-OH0644 sec-BuCH3CF3 HCl-Me-4-CHO-5-Cl0645 sec-BuCH3CF3 HCl3-Me-4-CHO-5-F0646 sec-BuCH3CF3 HCl3-Me-4-CH=NOH-5-Cl0647 sec-BuCH3CF3 HCl-Me-4-CH=NOH-5-F0648 sec-BuCH3CF3 HCl3-Me-4-CH=NOMe-5-Cl0649 sec-BuCH3CF3 HCl3-Me-4-CH=NOMe-5-F0650 sec-BuCH2CF3 HCl3-Me-4-CN-5-NH3 0651 sec-BuCH2CF3 HCl3-Me-4-CN-5-Cl0652 sec-BuCH3CF3 HCl3-Et-4-CN-5-NH3 0653 sec-BuCH3CF3 HCl3-Et-4-CN-5-Cl0654 sec-BuCH3CF3 HCl3-Me-4-Cl-5-CO2Et0655 sec-BuCH3CF3 HCl3-Et-4-Cl-5-CO2Et0656 sec-BuCH3CF3 HCl3-c-Pr-4-CN-5-NH3
    [0076] [Table 14]Compound NoRR1 R2 XYm0657 sec-BuCH2CF3 HCl3-c-Pr-4-CN-5-Cl0658 sec-BuCH3CF3 HCl3-CF3-4-Me-5-NH2 0659 sec-BuCH2CF3 HCl3-CF3-4-Me-5-Cl0660 sec-BuCH2CF3 HCl3-CF3-4-Cl-5-NH2 0661 sec-BuCH3CF3 HCl3-CF3-4,5-Cl2 0662 sec-BuCH3CF3 HCl3-CF3-4CHO-5-OH0663 sec-BuCH2CF3 HCl3-CF3-4-CHO-5-Cl0664 sec-BuCH2CF3 HCl3-CF3-4-CHO-5-F0665 sec-BuCH2CF3 HCl3-CF3-4-CH=NOH-5-Cl0666 sec-BuCH2CF3 HCl3-CF3-4-CH=NOH-5-F0667 sec-BuCH2CF3 HCl3-CF3-4-CH=NOMe-5-Cl0668 sec-BuCH2CF3 HCl3-CF3-4-CH=NOMe-5-F0669 sec-BuCH2CF3 HCl3-CF3-4-CN-5-NH2 0670 sec-BuCH2CF3 HCl3-CF3-4-CN-5-Cl0671 sec-BuCH2CF3 HCl3-CF3-4-CO2Me-5-NH2 0672 sec-BuCH2CF3 HCl3-CF3-4-CN-5-F0673 sec-BuCH2CF3 HCl3-CF3-4-CO3Me-5-Cl0674 sec-BuCH2CF3 HCl3-CF3-4-CO2H-5-NH2 0675 sec-BuCH2CF3 HCl3-CF3-4-CO2H-5-Cl0676 sec-BuCH2CF3 HCl3-CF3-4-CONH2-5-NH2 0677 sec-BuCH2CF3 HCl3-CF3-4-CONH2-5-Cl0678 sec-BuCH2CF3 HCl3-CF3-4-CONHMe-5-NH2 0679 sec-BuCH2CF3 HCl3-CF3-4-CONHMe-5-Cl0680 sec--BuCH2CF3 HCl3-CF3-4-CON(Me)2-5-Cl0681 sec-BuCH2CF3 HCl3-CF3-4-CON(Me)2-5-Cl0682 sec-BuCH2CF3 HCl3-CF3-4,5-(NH3)2 0683 sec--BuCH2CF3 HCl3-CF3-4-NH3-5-Cl0684 sec-BuCH2CF3 HCl3-CO2Et-4-Cl-5-NH2 0685 sec-BuCH2CF3 HCl3-CO2Et-4,5-Cl2 0686 sec-BuCH2CF3 HCl3-CO3H-4-Cl-5-NH3 0687 sec-BuCH2CF3 HCl3-CO2H-4,5-Cl2 0688 sec-BuCH2CF3 HCl3-CONH3-4-Cl-5-NH2 0689 sec-BuCH2CF3 HCl3-CONH3-4,5-Cl2 0690 sec-BuCH2CF3 HCl3-CONHMe-4-Cl-5-NH2 0691 sec-BuCH2CF3 HCl3-CONHMe-4,5-Cl2 0692 sec-BuCH2CF3 HCl3-CON(Me)2-4-Cl-5-NH2 0693 sec-BuCH2CF3 HCl3-CON(Me)2-4,5-Cl2 0694 sec-BuCH2CF3 HCl3-CN-4-Cl-5-NH2 0695 sec-BuCH2CF3 HCl3-CN-4,5-Cl2 0696 sec-BuCH2CF3 HCl3.5-(CH3)3-4-Cl0697 sec-BuCH2CF3 HCl3,4,5-Cl3 0698 sec-BuCH2CF3 HCl3-SMe4CN5-NH2 0699 sec-BuCH2CF3 HCl3-SMe-4-CN-5-Cl0700 sec-BuCH2CF3 HCl3-SOMe-4-CN-5-NH2 0701 sec-BuCH2CF3 HCl3-SOMe-4-CN-5-Cl0702 sec-BuCH2CF3 HCl3-SO2Me-4-CN-5-NH3 0703 sec-BuCH2CF3 HCl3-SO2Me-4-CN-5-Cl0704 sec-BuCH2CF3 HCl3-SH-4-CN-5-NHE0705 sec-RuCH2CF3 HCl3-SH-4-CN-5-Cl0706 sec-BuCH2CF3 HCl3-SCF3-4-CN-5-NH2 0707 sec-BuCH2CF3 HCl3-SCF3-4-CN-5-Cl
    [0077] [Table 15]Compound NoRR1 R2 XYm0708 sec-BuCH(Me)CF3 HH-0709 sec-BuCH(Me)CF3 HF-0710 sec-BuCH(Me)CF3 HCl-0711 sec-BuCH(Me)CF3 HBr-0712 sec-BuCH(Me)CF3 HI-0713 sec-BuCH(Me)CF3 HOH-0714 sec-BuCH(Me)CF3 HOMe-0715 sec-BuCH(Me)CF3 HOEt-0716 sec-BuCH(Me)CF3 HOCH3c-Pr-0717 sec-BuCH(Me)CF3 HOCHF2 -0718 sec-BuCH(Me)CF3 HOCF3 -0719 sec-BuCH(Me)CF3 HOCH2CF3 -0720 sec-BuCH(Me)CF3 HOCH2CF3 -0721 sec-BuCH(Me)CF3 HSMe-0722 sec-BuCH(Me)CF3 HSOMe-0723 sec-BuCH(Me)CF3 HSO2Me-0724 sec-BuCH(Me)CF3 HSCF3 -0725 sec-BuCH(Me)CF3 HSOCF3 -0726 sec-BuCH(Me)CF3 HSO2CF3 -0727 sec-BuCH(Me)CF3 HNH2 -0728 sec-BuCH(Me)CF3 HNHMe-0729 sec-BuCH(Me)CF3 HNHiso-Pr-0730 sec-BuCH(Me)CF3 HN(Me)3 -0731 sec-BuGH(Me)CF3 HN(Et)2 -0732 sec-BuCH(Me)CF3 HCN-0733 sec-BuCH(Me)CF3 HCHO-0734 sec-BuCH(Me)CF3 HOOMe-0735 sec-BuCH(Me)CF3 HCOEt-0736 sec-BuCH(Me)CF3 HCO3H-0737 sec-BuCH(Me)CF3 HCC2Me-0738 sec-BuCH(Me)CF3 HCO2Et-0739 sec-BuCH(Me)CF3 HCONH2 -0740 sec-BuCH(Me)CF3 HCONHMe-0741 sec-BuCH(Me)CF3 HCON(Me)2 -0742 sec-BuCH(Me)CF3 HMe-0743 sec-BuCH(Me)CF3 HEt-0744 sec-BuCH(Me)CF3 H iso-Pr-0745 sec-BuCH(Me)CF3 H c-Pr-0746 sec-BuCH(Me)CF3 HCH2F-0747 sec-BuCH(Me)CF3 HCH2Cl-0748 sec-BuCH(Me)CF3 HCH2Br-0749 sec-BuCH(Me)CF3 HCHF3 -0750 sec-BuCH(Me)CF3 HCF3 -0751 sec-BuCH(Me)CF3 HH-0752 sec-BuGH(Et)CF3 HF-0753 sec-BuCH(Et)CF3 HCl-0754 sec-BuCH(Et)CF3 HBr-0755 sec-BuCH(Et)CF3 HOMe-0756 sec-BuCH(Et)CF3 HCN-0757 sec-BuCH(Et)CF3 HMe-0758 sec-BuCH(Et)CF3 HCF3 -
    [0078] [Table 16]CompoundRR1 R2 XYm0759 sec-BuCH2CH2CF3 HH-0760 sec-BuCH2CH2CF3 HCl-0761 sec-BuCH2CH2CF3 HCN-0762 sec-BuCH2CH2CF3 HMe-0763 sec-BuCH3CH3CF3 HH-0764 sec-BuCH3CH3CF3 HCl-0765 sec-BuCH3CH3CF3 HCN-0766 sec-BuCH3CH3CF3 HMe-0767 sec-BuCH3CH(Me)CF3 HH-0768 sec-BuCH3CH(Me)CF3 HCl-0769 sec-BuCH3CH(Me)CF3 HCN-0770 sec-BuCH3CH(Me)CF3 HMe-0771 sec-BuCH3CH3CF3 HH-0772 sec-BuCH3CH3CF3 HCl-0773 sec-BuCH3CH3CF3 HCN-0774 sec-BuCH3CH3CF3 HMe-0775 sec-BuCH3 c-PrHH-0776 sec-BuCH3 c-PrHCl-0777 sec-BuCH3 c-PrHCN-0778 sec-BuCH3 c-PrHMe-0779 sec-BuCH2 c-PenHH-0780 sec-BuCH2 c-PenHCl-0781 sec-BuCH2 c-PenHCN-0782 sec-BuCH2 c-PenHMe-0783 sec-BuCH2 c-HexHH-0784 sec-BuCH2 c-HexHCl-0785 sec-BuCH2 c-HexHCN-0786 sec-BuCH2 c-HexHMe-0787 sec-BuCH2 c-HexHH-0788 sec-BuCH2 c-HexHCl-0789 sec-BuCH3CH3OHHCN-0790 sec-BuCH3CH3OHHMe-0791 sec-BuCH3CH3OMeHH-0792 sec-BuCH3CH3OMeHCl-0793 sec-BuCH3CH3OMeHCN-0794 sec-BuCH3CH3OMeHMe-0795 sec-BuCH3CH3OEtHH-0796 sec-BuCH3CH3OEtHCl-0797 sec-BuCH3CH3OEtHCN-0798 sec-BuCH3CH3OEtHMe-0799 sec-BuCH3CH3CH3OMeHH-0800 sec-BuCH2CH2CH2OMeHCl-0801 sec-BuCH2CH2CH2OMeHCN-0802 sec-BuCH2CH2CH2OMeHMe-0803 sec-BuCH2CH2NHMeHH-0804 sec-BuCH2CH2NHMeHCl-0805 sec-BuCH2CH2NHMeHCN-0806 sec-BuCH2CH2NHMeHMe-0807 sec-BuCH2CH2N(Me)2 HH-0808 sec-BuCH2CH2N(Me)2 HCl-0809 sec-BuCH2CH2N(Me)2 HCN-
    [0079] [Table 17]Compound NoRR1 R2 XYm0810 sec-BuCH2CH2N(Me)2 HMe-0811 sec-BuCH2CH2SMeHH-0812 sec-BuCH2CH2SMeHCl-0813 sec-BuCH2CH2SMeHCN-0814 sec-BuCH2CH2SMeHMe-0815 sec-BuCH2CH2SOMeHH-0816 sec-BuCH2CH2SOMeHCl-0817 sec-BuCH2CH2SOMeHCN-0818 sec-BuCH2CH2SOMeHMe-0819 sec-BuCH2CH2SO2MeHH-0820 sec-BuCH2CH2SO2MeHCl-0821 sec-BuCH2CH2SO2MeHCN-0822 sec-BuCH2CH2SO2MeHMe-0823 sec-BuCH2CNHH-0824 sec-BuCH2CNHCl-0825 sec-BuCH2CNHCN-0826 sec-BuCH2CNHMe-0827 sec-BuCH2CH2CNHH-0828 sec-BuCH2CH2CNHCl-0829 sec-BuCH2CH2CNHCN-0830 sec-BuCH2CH2CNHNe-0831 sec-BuCH2COMeHH-0832 sec-BuCH2COMeHCl-0833 sec-BuCH2COMeHCN-0834 sec-BuCH2COMeHMe-0835 sec-BuCH2CO2EtHH-0836 sec-BuCH2CO2EtHCl-0837 sec-BuCH2CO2EtHCN-0838 sec-BuCH2CO2EtHMe-0839 sec-BuCH(Me)CO2EtHH-0840 sec-BuCH(Me)CO2EtHCl-0841 sec-BuCH(Me)CO2EtHCN-0842 sec-BuCH(Me)CO2EtHMe-0843 sec-BuCH(iso-Pr)CO2EtHH-0844 sec-BuCH(iso-Pr)CO2EtHCl-0845 sec-BuCH(iso-Pr)CO2EtHCN-0846 sec-BuCH(iso-Pr)CO2EtHMe-0847 sec-BuCH2CONH2 HH-0848 sec-BuCH2CONH2 HCl-0849 sec-BuCH2CONH2 HCN-0850 sec-BuCH2CONH2 HMe-0851 sec-BuCH2CONHMeHH-0852 sec-BuCH2CONHMeHCl-0853 sec-BuCH2CONHMeHCN-0854 sec-BuCH2CONHMeHMe-0855 sec-BuCH2CON(Me)3 HH-0856 sec-BuCH2CON(Me)3 HCl-0857 sec-BuCH2CON(Me)2 HCN-0858 sec-BuCH2CON(Me)2 HMe-0859 sec-BuCH2CH=CH2 HH-0860 sec-BuCH2CH=CH2 HCl-
    [0080] [Table 18]Compound NoRR1 R2 XYm0861 sec-BuCH2CH=CH2 HCN-0862 sec-BuCH2CH=CH2 HMe-0863 sec-BuCH2C(Me)=CH2 HH-0864 sec-BuCH2C(Me)=CH2 HCl-0865 sec-BuCH2C(Me)=CH2 HCN-0866 sec-BuCH2C(Me)=CH2 HMe-0887 sec-BuCH2C≡CHHH-0868 sec-BuCH2C≡CHHCl-0869 sec-BuCH2C≡CHHCN-0870 sec-BuCH2C≡CHHMe-0871 sec-BuCOMeHH-0872 sec-BuCOMeHCl-0873 sec-BuCOMeHCN-0874 sec-BuCOMeHMe-0875 sec-BuCO2MeHH-0876 sec-BuCO2MeHCl-0877 sec-BuCO2MeHCN-0878 sec-BuCO2MeHMe-0879 sec-BuSO2MeHH-0880 sec-BuSO2MeHCl-0881 sec-BuSO2MeHCN-0882 sec-BuSO2MeHMe-0883 sec-BuSO3CH3 HH-0884 sec-BuSO3CH3 HCl-0885 sec-BuSO3CH3 HCN-0886 sec-BuSO3CH3 HMe-0887 sec-BuSO3CH3 HH-0888 sec-BuSO3CH3 HCl-0889 sec-BuSO3CH3 HCN-0890 sec-BuSO3CH3 HMe-0891 sec-BuSO3NHMeHH-0892 sec-BuSO3NHMeHCl-0893 sec-BuSO3NHMeHCN-0894 sec-BuSO3NHMeHMe-0896 sec-BuSO3N(Me)3 HH-0896 sec-BuSO3N(Me)3 HCl-0897 sec-BuSO3N(Me)3 HCN-0898 sec-BuSO3N(Me)3 HMe-0899 sec-BuOHHCl-0900 sec-BuOMeHCl-0901 sec-BuOEtHCl-0902 sec-BuOCH3CH=CH2 HCl-0903 sec-BuCH2PhHH-0904 sec-BuCH2PhHCl-0905 sec-BuCH2Si(Me)3 HH-0906 sec-BuCH2Si(Me)3 HCl-0907 sec-BuMeMeH-0908 sec-BuMeMeCl-0909 sec-BuMeMeCN-0910 sec-BuMeMeMe-0911 sec-BuMeCOMeCl-
    [0081] [Table 19]Compound NoRR1 R2 XYm0912 sec-BuMeCOOMeCl-0913 sec-BuMeSO2MeCl-0914 sec-BuMeSO2CF3 Cl-0915 sec-BuEtMeH-0916 sec-BuEtMeCl-0917 sec-BuEtMeCN-0918 sec-BuEtMeMe-0919 sec-BuEtEtH-0920 sec-BuEtEtF-0921 sec-BuEtEtCl-0922 sec-BuEtEtBr-0923 sec-BuEtEtI-0924 sec-BuEtEtOH-0925 sec-BuEtEtOMe-0926 sec-BuEtEtOEt-0927 sec-BuEtEtOCH3 c-Pr-0928 sec-BuEtEtOCHF3 -0929 sec-BuEtEtOCF3 -0930 sec-BuEtEtOCH2CHF3 -0931 sec-BuEtEtOCH2CF3 -0932 sec-BuEtEtSMe-0933 sec-BuEtEtSOMe-0934 sec-BuEtEtSO2Me-0935 sec-BuEtEtSCF3 -0936 sec-BuEtEtSOCF3 -0937 sec-BuEtEtSO2CF3 -0938 sec-BuEtEtNH2 -0939 sec-BuEtEtNHMe-0940 sec-BuEtEtNHMiso-Pr-0941 sec-BuEtEtN(Me)2 -0942 sec-BuEtEtN(Et)3 -0943 sec-BuEtEtCN-0944 sec-BuEtEtCHO-0945 sec-BuEtEtCOMe-0946 sec-BuEtEtCOEt-0947 sec-BuEtEtCO2H-0948 sec-BuEtEtCO3Me-0949 sec-BuEtEtCO2Et-0950 sec-BuEtEtCONH2 -0951 sec-BuEtEtCONHMe-0952 sec-BuEtEtCON(Me)2 -0953 sec-BuEtEtMe-0954 sec-BuEtEtEt-0955 sec-BuEtEt iso-Pr-0956 sec-BuEtEt c-Pr-0957 sec-BuEtEtCH2F-0958 sec-BuEtEtCH2Cl-0959 sec-BuEtEtCH2Br-0960 sec-BuEtEtCHF2 -0961 sec-BuEtEtCF3 -0962 sec-Bun-PrMeH-
    [0082] [Table 20]Compound NoRR1 R2 XYm0963 sec-Bu n-PrMeCl-0964 sec-Bu n-PrMeCN-0965 sec-Bu n-PrMeMe-0966 sec-Bu n-PrEtH-0967 sec-Bu n-PrEtCl-0968 sec-Bu n-PrEtCN-0969 sec-Bu n-PrEtMe-0970 sec-Bu n-Pr n-PrH-0971 sec-Bu n-Pr n-PrCl-0972 sec-Bu n-Pr n-PrCN-0973 sec-Bu n-Pr n-PrMe-0974 sec-Bu iso-PrMeH-0975 sec-Bu iso-PrMeCl-0976 sec-Bu iso-PrMeCN-0977 sec-Bu iso-PrMeMe-0978 sec-Bu iso-PrEtH-0979 sec-Bu iso-PrEtCl-0980 sec-Bu iso-PrEtCN-0981 sec-Bu iso-PrEtMe-0982 sec-Bu iso-Pr iso-PrH-0983 sec-Bu iso-Pr iso-PrCl-0984 sec-Bu iso-Pr iso-PrCN-0985 sec-Bu iso-Pr iso-PrMe-0986 sec-Bu n-BuMeH-0987 sec-Bu n-BuMeCl-0988 sec-Bu n-BuMeCN-0989 sec-Bu n-BuMeMe-0990 sec-Bu n-BuEtH-0991 sec-Bu n-BuEtCl-0992 sec-Bu n-BuEtCN-0993 sec-Bu n-BuEtMe-0994 sec-Bu iso-BuMeH-0995 sec-Bu iso-BuMeCl-0996 sec-Bu iso-BuMeCN-0997 sec-Bu iso-BuMeMe-0998 sec-BuCH3CF3 MeH-0999 sec-BuCH3CF3 MeF-1000 sec-BuCH3CF3 MeCl-1001 sec-BuCH3CF3 MeBr-1002 sec-BuCH3CF3 MeOMe-1003 sec-BuCH3CF3 MeCN-1004 sec-BuCH3CF3 MeMe-1005 sec-BuCH3CF3 MeCF3-1006 sec-BuCH3CF3 EtH-1007 sec-BuCH3CF3 EtF-1008 sec-BuCH3CH3 EtCl-1009 sec-BuCH3CF3 EtBr-1010 sec-BuCH3CF3 EtOMe-1011 sec-BuCH3CF3 EtCN-1012 sec-BuCH3CF3 EtMe-1013 sec-BuCH3CF3 EtCF3 -
    [0083] [Table 21]Compound NoRR1 R2 XYm1014 sec-BuCH3CF3 CH2OMeH-1015 sec-BuCH3CF3 CH3OMeCl-1016 sec-BuCH3CF3 CH2OMeCN-1017 sec-BuCH2CF3 CH2OMeMe-1018 sec-BuCH2CF3 CH2O(Me)=CH2 H-1019 sec-BuCH2CF3 CH2C(Me)=CH2 Cl-1020 sec-BuCH2CF3 CH2C(Me)=CH2 CN-1021 sec-BuCH2CF3 CH2O(Me)=CH2,Me-1022 sec-BuCH2CF3 COMeH-1023 sec-BuCH2CF3 COMeCl-1024 sec-BuCH2CF3 COMeCN-1025 sec-BuCH2CF3 COMeMe-1026 sec-BuCH2CF3 CO2 tert-BuH-1027 sec-BuCH2CF3 CO2 tert-BuCl-1028 sec-BuCH2CF3 CO2 tert-BuCN-1029 sec-BuCH2CF3 CO2 tert-BuMe-1030 sec-BuCH2CF3 SO2MeH-1031 sec-BuCH3CF3 SO2MECl-1032 sec-BuCH2F3 SO3MeCN-1033 sec-BuCH2CF3 SO2MeMe-1034 sec-BuCH2CF3 SO2CF3 H-1035 sec-BuCH2CF3 SO2CF3 Cl-1036 sec-BuCH2CF3 SO2CF3 CN-1037 sec-BuCH2CF3 SO2CF3 Me-1038 sec-BuCH(Me)CF3 MeH-1039 sec-BuCH(Me)CF3 MeCl-1040 sec-BuCH(Me)CF3 MeCN-1041 sec-BuCH(Me)CF3 MeMe-1042 sec-BuCH(Me)CF3 EtH-1043 sec-BuCH(Me)CF3 EtCl-1044 sec-BuCH(Me)CF3 EtCN-1045 sec-BuCH(Me)CF3 EtMe-1046 sec-BuCH(Me)CF3 CH2C(Me)=CH2 H-1047 sec-BuCH(Me)CF3 CH2C(Me)=CH2 Cl-1048 sec-BuCH(Me)CF3 CH2(Me)=CH2 CN-1049 sec-BuCH(Me)CF3 CH2C(Me)=CH2 Me-1050 sec-BuCH(Me)CF3 COMeH-1051 sec-BuCH(Me)CF3 COMeCl-1052 sec-BuCH(Me)CF3 COMeCN-1053 sec-BuCH(Me)CF3 COMeMe-1054 sec-BuCH(Me)CF3 COOtert-BuH-1055 sec-BuCH(Me)CF3 COOtert-BuCl-1056 sec-BuCH(Me)CF3 COOtert-BuCN-1057 sec-BuCH(Me)CF3 COOtert-BuMe-1058 sec-BuCH2CH=CH2 MeCl-1059 sec-BuCH3CH=CH2 EtCl-1060 sec-BuCH2C(Me)=CH2 MeCl-1061 sec-BuCH2C(Me)=CH3 EtCl-1062 sec-BuCH3C≡CHMeCl-1063 sec-BuCH3≡CHEtCl-1064 sec-BuCH2CH2OMeMeH-
    [0084] [Table 22]Compound NoRR1 R2 XYm1065 sec-BuCH3CH2OMeMeCl-1066 sec-BuCH2CH2OEtEtH-1067 sec-BuCH2CH2OEtEtCl-1068 sec-BuCH2CNMeCl-1069 sec-BuCH2CNEtCl-1070 sec-BuCH3CH2CNMeH-1071 sec-BuCH2CH2CNMeCl-1072 sec-BuCH2CH2CNEtH-1073 sec-BuCH2CH2CNEtCl-1074 sec-BuCH2CO2EtMeH-1075 sec-BuCH2CO2EtMeCl-1076 sec-BuCH2CO2EtEtH-1077 sec-BuCH2CO2EtEtCl-1078 sec-BuOHMeCl-1079 sec-BuOMeMeCl-1080 sec-BuOEtMeCl-1081 sec-Bu-(CH2)4-H-1082 sec-Bu-(CH2)4-Cl-1083 sec-Bu-(CH2)4-CN-1084 sec-Bu-(CH2)4-Me-1085 sec-Bu-CH(Me)(CH2)3-H-1086 sec-Bu-CH(Me)(CH2)3-F-1087 sec-Bu-CH(Me)(CH2)3-Cl-1088 sec-Bu-CH(Me)(CH2)3-Br-1089 sec-Bu-CH(Me)(CH2)3-OMe-1090 sec-Bu-CH(Me)(CH2)3-CN-1091 sec -Bu-CH(Me)(CH2)3-Me-1092 sec-Bu-CH(Me)(CH2)3-CF3 -1093 sec-Bu-CH(Me)(CH2)2-CH(Me)-H-1094 sec-Bu-CH(Me)(CH2)2-CH(Me)-Cl 1095 sec-Bu-CH(Me)(CH2)2-CH(Me)-CN-1096 sec-Bu-CH(Me)(CH2)2-CH(Me)-Me-1097 sec-BuCH2CH(Me)(CH2)3-H-1098 sec-BuCH2CH(Me)(CH2)2-Cl-1099 sec-BuCH2CH(Me)(CH2)2-CN-1100 sec-BuCH2CH(Me)(CH2)2-Me-1101 sec-Bu-CH2C(Me)2(CH2)2-H-1102 sec-Bu-CH2C(Me)2(CH2)2-Cl-1103 sec-Bu-CH2C(Me)2(CH2)2-CN-1104 sec-Bu-CH2C(Me)2(CH2)2-Me-1105 sec-Bu-CH2CH(OH)(CH2)2-H-1106 sec-Bu-CH2CH(OH)(CH2)2-Cl-1107 sec-Bu-CH2CH(OH)(CH2)2-CN-1108 sec-Bu-CH2CH(OH)(CH2)2-Me-1109 sec-BuCH2CHF(CH2)2-H-1110 sec-BuCH2CHF(CH2)2-Cl-1111 sec-BuCH2CHF(CH2)2-CN-1112 sec-BuCH2CHF(CH2)2-Me-1113 sec-Bu-CH(CF3)(CH2)3-H-1114 sec-Bu-CH(CF3)(CH2)3-F-1115 sec-Bu-CH(CF3)(CH2)3-Cl-
    [0085] [Table 23]Compound NoRR1 R2 XYm1116 sec-Bu-CH(CF3)(CH2)3-Br-1117 sec-BuOH(CF3(CH2)3-I-1118 sec-Bu-CH(CF3)(CH2)3-OH-1119 sec-Bu-CH(CF3)(CH2)3-OMe-1120 sec-Bu-CH(CF3)(CH2)3-OEt-1121 sec-Bu-CH(CF3)(CH2)3-OCHF2 -1122 sec-Bu-CH(CF3)(CH2)3-OCF3 -1123 sec-Bu-CH(CF3)(CH2)3-OCH2CHF3 -1124 sec-Bu-CH(CF3)(CH2)3-OCH2CF3 -1125 sec-Bu-CH(CF3)(CH2)3-SMe-1126 sec-Bu-CH(CF3)(CH2)3-SOMe-1127 sec-Bu-CH(CF3)(CH2)3-SO2Me-1128 sec-Bu-CH(CF3)(CH2)3-SCF3 -1129 sec-Bu-CH(CF3)(CH2)3-SOCF3 -1130 sec-Bu-CH(CF3)(CH2)3-SO2CF3 -1131 sec-Bu-CH(CF3)(CH2)3-NH2 -1132 sec-Bu-CH(CF3)(CH2)3-NHMe-1133 sec-Bu-CH(CF3)(CH2)3-NHiso-Pr-1134 sec-Bu-CH(CF3)(CH2)3-N(Me)2 -1135 sec-Bu-CH(CF3)(CH2)3-N(Et),-1136 sec-Bu-CH(CF3)(CH2)3-CN-1137 sec-Bu-CH(CF3)(CH2)3-CHO-1138 sec-Bu-CH(CF3)(CH2)3-COMe-1139 sec-Bu-CH(CF3)(CH2)3-COEt-1140 sec-Bu-CH(CF3)(CH2)3-CO2H-1141 sec-Bu-CH(CF3)(CH2)3-CO2Me-1142 sec-Bu-CH(CF3)(CH2)3-CO2Et-1143 sec-Bu-CH(CF3)(CH2)3-CONH2 -1144 sec-Bu-CH(CF3)(CH2)3-ONHMe-1145 sec-Bu-CH(CF3)(CH2)3-CON(Me)2 -1146 sec-Bu-CH(CF3)(CH2)3-Me-1147 sec-Bu-CH(CF3)(CH2)3-Et-1148 sec-Bu-CH(CF3)(CH2)3- iso-Pr-1149 sec-Bu-CH(CF3)(CH2)3- c-Pr-1150 sec-Bu-CH(CF3)(CH2)3-CH2F-1151 sec-Bu-CH(CF3)(CH2)3-CH3Cl-1152 sec-Bu-CH(CF3)(CH2)3-CH3Br-1153 sec-Bu-CH(CF3)(CH2)3-CHF2 -1154 sec-Bu-CH(CF3)(CH2)3-CF3 -1155 sec-Bu-CH2CF2(CH2)2-H-1156 sec-Bu-CH2CF2(CH2)2-Cl-1157 sec-Bu-CH2CF2(CH2)2-CN-1158 sec-Bu-CH2CF2(CH2)2-Me-1159 sec-Bu-CH2CF2(CH2)2-H-1160 sec-Bu-CH2CF2(CH2)2-Cl-1161 sec-Bu-CH2CF2(CH2)2-SMe-1162 sec-Bu-CH2CF2(CH2)2-SOMe-1163 sec-Bu-CH2CF2(CH2)2-SO2Me-1164 sec-Bu-CH2CF2(CH2)2-CN-1165 sec-Bu-CH2CF2(CH2)2-Me-1166 sec-Bu-CH2CH2(CO2Me)(CH2)2-H-
    [0086] [Table 24]Compound NoRR1 R2 XYm1167 sec-Bu-CH2CH(CO2Me)(CH2)2-Cl-1168 sec-Bu-CH2CH(CO2Me)(CH2)2-CN-1169 sec-Bu-CH2CH(CO2Me)(CH2)2-Me-1170 sec-Bu-CH3OCH3CH3-H-1171 sec-Bu-CH3OCH3CH3-Cl-1172 sec-Bu-CH3OCH3CH3-CN-1173 sec-Bu-CH3OCH3CH3-Me-1174 sec-Bu-CH3SCH3CH3-H-1175 sec-Bu-CH3SCH3CH3-Cl-1176 sec-Bu-CH2SCH2CH2-CN-1177 sec-Bu-CH2SCH2CH2-Me-1178 sec-Bu-(CH2)5-H-1179 sec-Bu-(CH2)5-Cl-1180 sec-Bu-(CH2)5-CN-1181 sec-Bu-(CH2)5-Me-1182 sec-Bu-CH(Me)(CH3)4-H-1183 sec-Bu-CH(Me)(CH3)4-Cl-1184 sec-Bu-CH(Me)(CH2)4-CN-1185 sec-Bu-CH(Me)(CH2)4-Me-1186 sec-Bu-CH2CH(Me)(CH2)3-H-1187 sec-Bu-CH2CH(Me)(CH2)3-Cl-1188 sec-Bu-CH2CH(Me)(CH2)3-CN-1189 sec-Bu-CH2CH(Me)(CH2)3-Me-1190 sec-Bu-(CH2)2CH(Me)(CH2)2-H-1191 sec-Bu-(CH2)2CH(Me)(CH2)2-F-1192 sec-Bu-(CH2)2CH(Me)(CH2)2-Cl-1193 sec-Bu-(CH2)2CH(Me)(CH2)2-Br-1194 sec-Bu-(CH2)2CH(Me)(CH2)2-I-1195 sec-Bu-(CH2)2CH(Me)(CH2)2-OH-1196 sec-Bu-(CH2)2CH(Me)(CH2)2-OMe-1197 sec-Bu-(CH2)2CH(Me)(CH2)2-OEt-1198 sec-Bu-(CH2)2CH(Me)(CH2)2-OCH2 c-Pr-1199 sec-Bu-(CH2)2CH(Me)(CH2)2-OCH2Ph-1200 sec-Bu-(CH2)2CH(Me)(CH2)2-OCHF2 -1201 sec-Bu-(CH2)2CH(Me)(CH2)2-OCF3 -1202 sec-Bu-(CH2)2CH(Me)(CH2)2-OCH2CHF2 -1203 sec-Bu-(CH2)2CH(Me)(CH2)2-OCH3CF3 -1204 sec-Bu-(CH2)2CH(Me)(CH2)2-SMe-1205 sec-Bu-(CH2)2CH(Me)(CH2)2-SOMe-1206 sec-Bu-(CH2)2CH(Me)(CH2)2-SO3Me-1207 sec-Bu-(CH2)2CH(Me)(CH2)2-SCF3 -1208 sec-Bu-(CH2)2CH(Me)(CH2)2-SOCF3 -1209 sec-Bu-(CH2)2CH(Me)(CH2)2-SO2CF3 -1210 sec-Bu-(CH2)2CH(Me)(CH2)2-NH2 -1211 sec-Bu-(CH2)2CH(Me)(CH2)2-NHMe-1212 sec-Bu-(CH2)2CH(Me)(CH2)2-NHiso-Pr-1213 sec-Bu-(CH2)2CH(Me)(CH2)2-N(Me)2 -1214 sec-Bu-(CH2)2CH(Me)(CH2)2-N(Et)2 -1215 sec-Bu-(CH2)2CH(Me)(CH2)2-CN-1216 sec-Bu-(CH2)2CH(Me)(CH2)2-CHO-1217 sec-Bu-(CH2)2CH(Me)(CH2)2-COMe-
    [0087] [Table 25]Compound NoRR1 R2 XYm1218 sec-Bu-(CH2)2CH(Me)(CH2)2-COEt-1219 sec-Bu-(CH2)2CH(Me)(CH2)2-CO2H-1220 sec-Bu-(CH2)2CH(Me)(CH2)2-CO2Me-1221 sec-Bu-(CH2)2CH(Me)(CH2)2-CO2Et-1222 sec-Bu-(CH2)2CH(Me)(CH2)2-CONH2 -1223 sec-Bu-(CH2)2CH(Me)(CH2)2-ONHMe-1224 sec-Bu-(CH2)2CH(Me)(CH2)2-CON(Me)2 -1225 sec-Bu-(CH2)2CH(Me)(CH2)2-Me-1226 sec-Bu-(CH2)2CH(Me)(CH2)2-Et-1227 sec-Bu-(CH2)2CH(Me)(CH2)2- iso-Pr-1238 sec-Bu-(CH2)2CH(Me)(CH2)2- c-Pr-1229 sec-Bu-(CH2)2CH(Me)(CH2)2-CH2F-1230 sec-Bu-(CH2)2CH(Me)(CH2)2-CH2Cl-1231 sec-Bu-(CH2)2CH(Me)(CH2)2-CH2Br-1232 sec-Bu-(CH2)2CH(Me)(CH2)2-CHF2 -1233 sec-Bu-(CH2)2CH(Me)(CH2)2-CF3 -1234 sec-Bu-(CH2)2CH(Me)(CH2)2-H3-Cl1235 sec-Bu-(CH2)2CH(Me)(CH2)2-Cl3-Cl1236 sec-Bu-(CH2)2CH(Me)(CH2)2-CN3-Cl1237 sec-Bu-(CH2)2CH(Me)(CH2)2-Me3-Cl1338 sec-Bu-(CH2)2CH(Me)(CH2)2-H3-Me1339 sec-Bu-(CH2)2CH(Me)(CH2)2-Cl3-Me1240 sec-Bu-(CH2)2CH(Me)(CH2)2-CN3-Me1241 sec-Bu-(CH2)2CH(Me)(CH2)2-Me3-Me1242 sec-Bu-(CH2)2CH(Me)(CH2)2-H3-Pr-i1243 sec-Bu-(CH2)2CH(Me)(CH2)2-Cl3-Pr-i1244 sec-Bu-(CH2)2CH(Me)(CH2)2-CN3-Pr-i1245 sec-Bu-(CH2)2CH(Me)(CH2)2-Me3-Pr-i1246 sec-Bu-(CH2)2CH(Me)(CH2)2-H3-CF3-4-CO2Et1247 sec-Bu-(CH2)2CH(Me)(CH2)2-Cl3-CF3-4-CO2Et1248 sec-Bu-(CH2)2CH(Me)(CH2)2-CN3-CF3-4-CO2Et1249 sec-Bu-(CH2)2CH(Me)(CH2)2-Me3-CF3-4-CO2Et1250 sec-Bu-(CH2)2CH(Me)(CH2)2-H3,5-(Me)2 1251 sec-Bu-(CH2)2CH(Me)(CH2)2-Cl3,5-(Me)2 1252 sec-Bu-(CH2)2CH(Me)(CH2)2-CN3,5-(Me)2 1253 sec-Bu-(CH2)2CH(Me)(CH2)2-Me3,5-(Me)2 1254 sec-Bu-(CH2)2O(CH2)2-H-1255 sec-Bu-(CH2)2O(CH2)2-Cl-1256 sec-Bu-(CH2)2O(CH2)2-CN-1257 sec-Bu-(CH2)2O(CH2)2-Me-1258 sec-Bu-CH2CH(Me)OCH(Me)CH2-H-1259 sec-Bu-CH2CH(Me)OCH(Me)CH2-Cl-1260 sec-Bu-CH2CH(Me)OCH(Me)CH2-CN-1261 sec-Bu-CH2CH(Me)OCH(Me)CH2-Me-1262 sec-Bu-(CH2)2S(CH2)2-H-1263 sec-Bu-(CH2)2S(CH2)2-Cl-1264 sec-Bu-(CH2)2S(CH2)2-CN-1265 sec-Bu-(CH2)2S(CH2)2-Me-1266 sec-Bu-(CH2)2S(CH2)2-H-1267 sec-Bu-(CH2)2S(CH2)2-Cl-1268 sec-Bu-(CH2)2S(CH2)2-CN-
    [0088] [Table 26]Compound NoRR1 R2 XYm1269 sec-Bu-(CH2)2S(O)(CH2)2-Me-1270 sec-Bu-(CH2)2S(O)(CH2)2-H-1271 sec-Bu-(CH2)2S(O)(CH2)2-Cl-1272 sec-Bu-(CH2)2S(O)(CH2)2-CN-1273 sec-Bu-(CH2)2S(O)(CH2)2-Me-1274 sec-Bu-(CH2)2S(O)(CH2)2-H-1275 sec-Bu-(CH2)2S(O)(CH2)2-Cl-1276 sec-Bu-(CH2)2S(O)(CH2)2-CN-1277 sec-Bu-(CH2)2S(O)(CH2)2-Me-1278 iso-Bu iso-PrHH-1279 iso-Bu iso-PrHCl-1280 iso-Bu iso-PrHCN-1281 iso-Bu iso-PrHMe-1282 iso-BuCH2CF3 HH-1283 iso-BuCH2CF3 HCl-1284 iso-BuCH2CF3 HCN-1285 iso-BuCH2CF3 HMe-1286 iso-BuEtEtH-1287 iso-BuEtEtCl-1388 iso-BuEtEtCN-1289 iso-BuEtEtMe-1290 iso-Bu-(CH2)2CH(Me)(CH3)2-H-1291 iso-Bu-(CH2)2CH(Me)(CH3)2-Cl-1292 iso-Bu-(CH2)2CH(Me)(CH3)2-CN-1293 iso-Bu-(CH2)2CH(Me)(CH3)2-Me-1294 n-Pen iso-PrHH-1295 n-Pen iso-PrHCl-1296 n-Pen iso-PrHCN-1297 n-Pen iso-PrHMe-1298 n-PenCH2CF3 HH-1299 n-PenCH2CF3 HCl-1300 n-PenCH2CF3 HCN-1301 n-PenCH2CF3 HMe-1302 n-PenEtEtH-1303 n-PenEtEtCl-1304 n-PenEtEtCN-1305 n-PenEtEtMe-1306 n-Pen-(CH2)2CH(Me)(CH2)2-H-1307 n-Pen-(CH2)2CH(Me)(CH2)2-Cl-1308 n-Pen-(CH2)2CH(Me)(CH2)2-CN-1309 n-Pen-(CH2)2CH(Me)(CH2)2-Me-13102-Pen iso-PrHH-13112-Pen iso-PrHCl-13122-Pen iso-PrHCN-13132-Pen iso-PrHMe-13142-PenCH2CF3 HH-13152-PenCH2CF3 HCl-13162-PenCH2CF3 HCN-13172-PenCH2CF3 HMe-13182-PenEtEtH-13192-PenEtEtCl-
    [0089] [Table 27]Compound NoRR1 R2 XYm13202-PenEtEtCN-13212-PenEtEtMe-13222-Pen-(CH2)2CH(Me)(CH2)2-H-13232-Pen-(CH2)2CH(Me)(CH2)2-Cl-13242-Pen-(CH2)2CH(Me)(CH2)2-CN-13252-Pen-(CH2)2CH(Me)(CH2)2-Me-13263-Pen iso-PrHH-13273-Pen iso-PrHF-13283-Pen iso-PrHCl-13293-Pen iso-PrHBr-13303-Pen iso-PrHCN-13313-Pen iso-PrHMe-13323-Pen iso-PrHCF3 -13333-Pen tert-BuHH-13343-Pen tert-BuHF-13353-Pen tert-BuHCl-13363-Pen tert-BuHBr-13373-Pen tert-BuHCN-13383-Pen tert-BuHMe-13393-Pen tert-BuHCF3 -13403-PenCH2CF3 HH-13413-PenCH2CF3 HF-13423-PenCH2CF3 HCl-13433-PenCH2CF3 HBr-13443-PenCH2CF3 HI-13453-PenCH2CF3 HOH-13463-PenCH2CF3 HOMe-13473-PenCH2CF3 HOEt-13483-PenCH2CF3 HOCH2 c-Pr-13493-PenCH2CF3 HOCHF2 -13503-PenCH2CF3 HOCF3 -13513-PenCH2CF3 HOCH2CHF2 -13523-PenCH2CF3 HOCH3CF3 -13533-PenCH2CF3 HSMe-13543-PenCH2CF3 HSOMe-13553-PenCH2CF3 HSO2Me-13563-PenCH2CF3 HSCF3 -13573-PenCH2CF3 HSOCF3 -13583-PenCH2CF3 HSO2CF3 -13593-PenCH2CF3 HNH2 -13603-PenCH2CF3 HNHMe-13613-PenCH2CF3 HNHiso-Pr-13623-PenCH2CF3 HN(Me)2 -13633-PenCH2CF3 HN(Et),-13643-PenCH2CF3 HCN-13653-PenCH2CF3 HCHO-13663-PenCH2CF3 HCOMe-13673-PenCH2CF3 HCOEt-13683-PenCH2CF3 HCO2H-13693-PenCH2CF3 HCO2Me-13703-PenCH2CF3 HCO2Et-
    [0090] [Table 28]Compound NoRR1 R2 XYm13713-PenCH2CF3 HCONH3 -13723-PenCH2CF3 HODNHMe-13733-PenCH2CF3 HCON(Me)3 -13743-PenCH2CF3 HMe-13753-PenCH2CF3 HEt-13763-PenCH2CF3 H iso-Pr-13773-PenCH2CF3 H c-Pr-13783-PenCH2CH3 HCH3F-13793-PenCH2CF3 HCH2Cl-13803-PenCH2CF3 HCH3Br-13813-PenCH2CF3 HCHF3 -13823-PenCH2CF3 HCF3 -13833-PenCH(Me)CF3 HH-13843-PenCH(Me)CF3 HF-13853-PenCH(Me)OF3 HCl-13863-PenCH(Me)CF3 HBr-13873-PenCH(Me)CF3 HI-13883-PenCH(Me)CF3 HOH-13893-PenCH(Me)CF3 HOMe-13903-PenCH(Me)CF3 HOEt-13913-PenCH(Me)CF3 HOCH3-Pr-13923-PenCH(Me)CF3 HOCHF3 -13933-PenCH(Me)CF3 HOCF3 -13943-PenCH(Me)CF3 HOCH2CHF3 -13953-PenCH(Me)CF3 HOCH2CF3 -13963-PenCH(Me)CF3 HSMe-13973-PenCH(Me)CF3 HSOMe-13983-PenCH(Me)CF3 HSO3Me-13993-PenCH(Me)CF3 HSCF3 -14003-PenCH(Me)CF3 HSOCF3 -14013-PenCH(Me)CF3 HSO3CF3 -14023-PenCH(Me)CF3 HNH3 -14033-PenCH(Me)CF3 HNHMe-14043-PenCH(Me)CF3 HNHiso-Pr-14053-PenCH(Me)CF3 HN(Me)3 -14063-PenCH(Me)CF3 HN(Et)3 -14073-PenCH(Me)CF3 HCN-14083-PenCH(Me)CF3 HCHO-14093-PenCH(Me)CF3 HCOMe-14103-PenCH(Me)CF3 HCOEt-14113-PenCH(Me)CF3 HCO3H-14123-PenCH(Me)CF3 HCO3Me-14133-PenCH(Me)CF3 HCO3Et-14143-PenCH(Me)CF3 HVONH3 -14153-PenCH(Me)CF3 HCONHMe-14163-PenCH(Me)CF3 HCON(Me)3 -14173-PenCH(Me)CF3 HMe-14183-PenCH(Me)CF3 HEt-14193-PenCH(Me)CF3 H iso-Pr-14203-PenCH(Me)CF3 H c-Pr-14213-PenCH(Me)CF3 HCH3F-
    [0091] [Table 29]Compound NoRR1 R2 XYm14223-PenCH(Me)CF3 HCH3Cl-14233-PenCH(Me)CF3 HCH3Br-14243-PenCH(Me)CF3 HCHF3 -14253-PenCH(Me)CF3 HCF3 -14263-PenEtEtH-14273-PenEtEtF-14283-PenEtEtCl 14293-PenEtEtBr-14303-PenEtEtCN-14313-PenEtEtMe-14323-PenEtEtCF3 -14333-Pen-CH(CF3)(CH2)3-H-14343-Pen-CH(CF3)(CH2)3-F-14353-Pen-CH(CF3)(CH2)3-Cl-14363-Pen-CH(CF3)(CH2)3-Br-14373-Pen-CH(CF3)(CH2)3-CN-14383-Pen-CH(CF3)(CH2)3-Me-14393-Pen-CH(CF3)(CH2)3-CF3 -14403-Pen-(CH2)3CH(Me)(CH2)3-H-14413-Pen-(CH2)3CH(Me)(CH2)3-F-14423-Pen-(CH2)3CH(Me)(CH2)3-Cl-14433-Pen-(CH2)3CH(Me)(CH2)3-Br-14443-Pen-(CH2)3CH(Me)(CH2)3-CN-14453-Pen-(CH2)3CH(Me)(CH2)3-Me-14463-Pen-(CH2)3CH(Me)(CH2)3-CF3 -1447 tert-Bu iso-PrHH-1448 tert-Bu iso-PrHCl-1449 tert-Bu iss-PrHCN-1450 tert-Bu iso-PrHMe-1451 tert-BuCH2CF3 HH-1452 tert-BuCH2CF3 HCl-1453 tert-BuCH2CF3 HCN-1454 tert-BuCH2CF3 HMe-1455tert-BuEtEtH-1456 tert-BuEtEtCl-1457 tert-BuEtEtCN-1458 tert-BuEtEtMe-1459 tert-Bu-(CH2)3CH(Me)(CH2)3-H-1460 tert-Eu-(CH2)3CH(Me)(CH2)3-Cl-1461 tert-Bu-(CH2)3CH(Me)(CH2)3-CN-1462 tert-Bu-(CH2)3CH(Me)(CH2)3-Me-1463C(Me)3Et iso-PrHH-1464C(Me)3Et iso-PrHCl-1465C(Me)3Et iso-PrHCN-1466C(Me)3Et iso-PrHMe-1467C(Me)3EtCH2CF3 HH-1468C(Me)3EtCH2CF3 HCl-1469C(Me)3EtCH2CF3 HCN-1470C(Me)3EtCH2CF3 HMe-1471C(Me)3EtEtEtH-1472C(Me)2EtEtEtCl-
    [0092] [Table 30]Compound NoRR1 R2 XYm1473C(Me)2EtEtEtCN-1474C(Me)3EtEtEtMe-1475C(Me)3Et-(CH2)3CH(Me)(CH2)3-H-1476C(Me)3Et-(CH2)3CH(Me)(CH2)3-Cl-1477C(Me)-Et-(CH2)3CH(Me)(CH2)3-CN-1478C(Me)3Et-(CH2)3CH(Me)(CH2)3-Me 1479 c-Pr iso-PrHH-1480 c-Pr iso-PrHCl-1481 c-Pr iso-PrHCN-1482 c-Pr iso-PrHMe-1483 c-PrCH2CF3 HH-1484 c-PrCH2CF3 HCl-1485 c-PrCH2CF3 HCN-1486 c-PrCH2CF3 HMe-1487 c-PrEtEtH-1488 c-PrEtEtCl-1489 c-PrEtEtCN-1490 c-PrEtEtMe-1491 c-Pr-(CH2)3CH(Me)(CH2)3-H-1492 c-Pr-(CH2)3CH(Me)(CH2)3-Cl 1493 c-Pr-(CH2)3CH(Me)(CH2)3-CN-1494 c-Pr-(CH2)3CH(Me)(CH2)3-Me-1495 c-Pen iso-PrHH-1496 c-Pen iso-PrHF-1497 c-Pen iso-PrHCl-1498 c-Pen iso-PrHBr-1499 c-Pen iso-PrHCN-1500 c-Pan iso-PrHMe-1501 c-Pen iso-PrHCF3 -1502 c-Pen tert-BuHH-1503 c-Pen tert-BuHF-1504 c-Pen tert-BuHCl-1505 c-Pen tert-BuHBr-1506 c-Pen tert-BuHCN-1507 c-Pon tert-BuHMe-1508 c-Pen tert-BuHCF3 -1509 c-PenCH2CF3 HH-1510 c-PenCH2CF3 HF-1511 c-PenCH2CF3 HCl-1512 c-PenCH2CF3 HBr-1513 c-PenCH2CF3 HI-1514 c-PenCH2CF3 HOH-1515 c-PenCH2CF3 HOMe-1516 c-PenCH2CF3 HOEt-1517 c-PenCH2CF3 HOCH3 c-Pr-1518 c-PonCH2CF3 HOCHF3 -1519 c-PenCH2CF3 HOCF3 -1520 c-PenCH2CF3 HOCH2CHF3 -1521 c-PenCH2CF3 HOCH2CF3 -1522 c-PenCH2CF3 HSMe-1523 c-PenCH2CF3 HSOMe-
    [0093] [Table 31]Compound NoRR1 R2 XYm1624 c-PenCH2CF3 HSO2Me-1525 c-PenCH2CF3 HSCF3 -1526 c-PenCH2CF3 HSOCF3 -1527 c-PenCH2CF3 HSO2CF3 -1528 c-PenCH2CF3 HNH3 -1529 c-PenCH2CF3 HNHMe-1530 c-PenCH2CF3 HNHiso-Pr-1531 c-PenCH2CF3 HN(Me)3 -1532 c-PenCH2CF3 HN(Et)2 -1533 c-PenCH2CF3 HCN-1534 c-PenCH2CF3 HCHO-1535 c-PenCH2CF3 HCOMe-1536 c-PenCH2CF3 HCOEt-1637 c-PenCH2CF3 HCO3H-1538 c-PenCH2CF3 HCO3Me-1539 c-PenCH2CF3 HCO3Et-1540 c-PenCH2CF3 HCONH3,-1541 c-PenCH2CF3 HCONHMe-1542 c-PenCH2CF3 HCON(Me)2 -1543 c-PenCH2CF3 HMe-1544 c-PenCH2CF3 HEt-1545 c-PenCH2CF3 H iso-Pr-1546 c-PenCH2CF3 H c-Pr-1547 c-PenCH2CF3 HCH3F-1548 c-PenCH2CF3 HCH2Gl-1549 c-PenCH2CF3 HCH3Br-1550 c-PenCH2CF3 HCHF3 -1551 c-PenCH2CF3 HCF3 -1552 c-PenCH(Me)CF3 HH-1553 c-PenCH(Me)CF3 HF-1554 c-PenCH(Me)CF3 HCl-1555 c-PenCH(Me)CF3 HBr-1556 c-PenCH(Me)CF3 HI-1557 c-PenCH(Me)CF3 HOH-1558 c-PenCH(Me)CF3 HCMe-1559 c-PenCH(Me)CF3 HOEt-1560 c-PenCH(Me)CF3 HOCH3 c-Pr-1561 c-PenCH(Me)CF3 HOCHF2 -1562 c-PenCH(Me)CF3 HOCF3 -1563 c-PenCH(Me)CF3 HOOH2CHF3 -1564 c-PenCH(Me)CF3 HOCH2CF3 -1565 c-PenCH(Me)CF3 HSMe-1566 c-PenCH(Me)CF3 HSOMe-1567 c-PenCH(Me)CF3 HSO3Me-1568 c-PenCH(Me)CF3 HSCF3 -1569 c-PenCH(Me)CF3 HSOCF3 -1579 c-PenCH(Me)CF3 HSO2CF3 -1571 c-PenCH(Me)CF3 HNH3 -1572 c-PenCH(Me)CF3 HNHMe-1573 c-PenCH(Me)CF3 HNHiso-Pr-1574 c-PenCH(Me)CF3 HN(Me)2 -
    [0094] [Table 32]Compound NoRR1 R3 XYm1575 c-PenCH(Me)CF3 HN(Et)2 -1576 c-PenCH(Me)CF3 HCN-1577 c-penCH(Me)CF3 HCHO-1578 c-PenCH(Me)CF3 HCOMe-1579 c-PenCH(Me)CF3 HCOEt-1580 c-penCH(Me)CF3 HCO3H-1581 c-PenCH(Me)CF3 HCC3Me - 1582 c-penCH(Me)CF3 HCC3Et-1583 c-PenCH(Me)CF3 HCONH3 -1584 c-PenCH(Me)OF3 HCONHMe-1585 c-PenCH(Me)CF3 HCON(Me)3 -1586 c-PenCH(Me)CF3 HMe - 1587 c-PenCH(Me)CF3 HEt-1588 c-PenCH(Me)CF3 H iso-Pr-1589 c-PenCH(Me)CF3 H c-Pr-1590 c-PenCH(Me)CF3 HCH3F-1591 c-PenCH(Me)CF3 HCH3Cl-1592 c-PenCH(Me)CF3 HCH3Br-1593 c-PenCH(Me)CF3 HCHF3 -1594 c-PenCH(Me)CF3 HCF3 -1595 c-PenEtEtH-1596 c-PenEtEtF-1597 c-PenEtEtCl-1598 c-PenEtEtBr-1599 c-PenEtEtCN-1600 c-PenEtEtMe-1601 c-PenEtEtCF3 -1602 c-PenCH(CF3)(CH3)3-H-1603 c-PenCH(CF3)(CH3)3-F-1604 c-PenCH(CF3)(CH3)3-Cl-1605 c-PenCH(CF3)(CH3)3-Br-1606 c-PenCH(CF3)(CH3)3-CN-1607 c-PenCH(CF3)(CH3)3-Me-1608 c-PenCH(CF3)(CH3)3-CF3 -1609 c-PenCH(CF3)(CH3)3-H-1610 c-PenCH(CF3)(CH3)3-F-1611 c-PenCH(CF3)(CH3)3-Cl - 1612 c-PenCH(CF3)(CH3)3-Br-1613 c-PenCH(CF3)(CH3)3-CN-1614 c-PenCH(CF3)(CH3)3-Me-1615 c-PenCH(CF3)(CH3)3-CF3 -1616 c-Hex iso-PrHH-1617 c-Hex iso-PrHCl-1618 c-Hex iso-PrHCN-1619 c-Hex iso-PrHMe-1620 c-HexCH3CF3 HH-1621 c-HexCH3CF3 HCl-1622 c-HexCH3CF3 HCN-1623 c-HexCH3CF3 HMe-1624 c-HexEtEtH-1625 c-HexEtEtCl-
    [0095] [Table 33]Compound NoRR1 R3 XYm1626 c-HexEtEtCN-1627 c-HexEtEtMe-1628 c-Hex-(CH2)2CH(Me)(CH2)2-H-1629 c-Hex-(CH2)2CH(Me)(CH2)2-Cl - 1630c-Hex-(CH2)2CH(Me)(CH2)2-CN-1631 c-Hex-(CH2)2CH(Me)(CH2)2-Me-1632CH3 c-Pr iso-PrHH-1633CH3 c-Pr iso-PrHCl-1634CH3 c-Pr iso-PrHCN-1635CH3 c-Pr iso-PrHMe-1636CCH3 c-PrCH2CF3 HH-1637CH3 c-PrCH2CF3 HCl-1638CH3 c-PrCH2CF3 HCN-1639CH3 c-PrCH2CF3 HMe-1640CH3 c-PrEtEtH-1641CH3 c-PrEtEtCl-1642CH3 c-PrEtEtCN-1643CH3 c-PrEtEtMe-1644CH3 c-Pr-(CH2)2CH(Me)(CH2)2-H-1645CH3 c-Pr-(CH2)2CH(Me)(CH2)2-Cl-1646CH3 c-Pr-(CH2)2CH(Me)(CH2)2-CN-1647CH3 c-Pr-(CH2)2CH(Me)(CH2)2-Me-1648CH3 c-Pr iso-PrHH-1649CH3CF3 iso-PrHCl-1650CH3CF3 iso-PrHCN-1651CH3CF3 iso-PrHMe-1652CH2CF3 CH2CF3 HH-1653CH2CF3 CH2CF3 HCl-1654CH2CF3 CH2CF3 HCN-1655CH2CF3 CH2CF3 HMe-1656CH2CF3 EtEtH-1657CH2CF3 EtEtCl-1658CH2CF3 EtEtCN-1659CH2CF3 EtEtMe-1660CH2CF3 -(CH2)2CH(Me)(CH2)2-H-1661CH2CF3 -(CH2)2CH(Me)(CH2)2-Cl-1662CH2CF3 -(CH2)2CH(Me)(CH2)2-CN-1663CH2CF3 -(CH2)2CH(Me)(CH2)2-Me-1664CF(Me)3 iso-PrHH-1666CF(Me)3 iso-PrHCl-1666CF(Me)3 iso-PrHCN-1667CF(Me)3 iso-PrHMe-1668CF(Me)3 CH3CF3 H-1669CF(Me)3 CH3CF3 HCl-1670CF(Me)3 CH3CF3 HCN-1671CF(Me)3 CH3CF3 HMe-1672CF(Me)3 EtEtH-1673CF(Me)3 EtEtCl-1674CF(Me)3 EtEtCN-1675CF(Me)3 EtEtMe-1676CF(Me)3 -(CH2)2CH(Me)(CH2)2-H-
    [0096] [Table 34]Compound NoRR1 R3 XYm1677CF(Me)3 -(CH2)2CH(Me)(CH2)2-Cl-1678CF(Me)3 -(CH2)2CH(Me)(CH2)2-CN-1679CF(Me)3 -(CH2)2CH(Me)(CH2)2-Me-1680CF(Me)Et iso-PrHH-1681CF(Me)Et iso-PrHCl-1682CF(Me)Et iso-PrHCN-1683CF(Me)Et iso-PrHMe-1684CF(Me)EtCH2CF3 HH-1685CF(Me)EtCH2CF3 HCl-1686CF(Me)EtCH2CF3 HCN-1687CF(Me)EtCH2CF3 HMe-1688CF(Me)EtEtEtH-1689CF(Me)EtEtEtCl-1690CF(Me)EtEtEtCN-1691CF(Me)EtEtEtMe-1692CF(Me)Et-(CH2)2CH(Me)(CH2)2-H-1693CF(Me)Et-(CH2)2CH(Me)(CH2)2-Cl-1694CF(Me)Et-(CH2)2CH(Me)(CH2)2-CN-1695CF(Me)Et-(CH2)2CH(Me)(CH2)2-Me-1696CF(CF3)2 iso-PrHH-1697CF(CF3)2 iso-PrHCl-1698CF(CF3)2 iso-PrHCN-1699CF(CF3)2 iso-PrHMe-1700CF(CF3)2 CH2CF3 HH-1701CF(CF3)2 CH2CF3 HCl 1702CF(CF3)2 CH2CF3 HCN-1703CF(CF3)2 CH2CF3 HMe-1704CF(CF3)2 EtEtH-1705CF(CF3)2 EtEtCl-1706CF(CF3)2 EtEtCN-1707CF(CF3)2 EtEtMe-1708CF(CF3)2 -(CH2)2CH(Me)(CH2)2-H-1709CF(CF3)2 -(CH2)2CH(Me)(CH2)2-Cl-1710CF(CF3)2 -(CH2)2CH(Me)(CH2)2-CN-1711CF(CF3)2 -(CH2)2CH(Me)(CH2)2-Me-1712CH3OH iso-PrHH-1713CH3OH iso-PrHCl-1714CH3OH iso-PrHCN-1715CH3OH iso-PrHMe-1716CH3OHCH2CF3 HH-1717CH3OHCH2CF3 HCl-1718CH3OHCH2CF3 HCN-1719CH3OHCH2CF3 HMe-1720CH3OHEtEtH-1721CH3OHEtEtCl-1722CH3OHEtEtCN-1723CH3OHEtEtMe-1724CH3OH-(CH2)2CH(Me)(CH2)2-H-1725CH3OH-(CH2)2CH(Me)(CH2)2-Cl-1726CH3OH-(CH2)2CH(Me)(CH2)2-CN-1727CH3OH-(CH2)2CH(Me)(CH2)2-Me-
    [0097] [Table 35]Compound NoRR1 R2 XYm1728CH(OH)Me iso-PrHH-1729CH(OH)Me iso-PrHCl-1730CH(OH)Me iso-PrHCN-1731CH(OH)Me iso-PrHMe-1732CH(OH)MeCH3CF3 HH-1733CH(OH)MeCH3CF3 HCl-1734CH(OH)MeCH3CF3 HCN-1735CH(OH)MeCH3CF3 HMe-1736CH(OH)MeEtEtH-1737CH(OH)MeEtEtCl-1738CH(OH)MeEtEtCN 1739CH(OH)MeEtEtMe-1740CH(OH)Me-(CH2)2CH(Me)(CH2)2-H-1741CH(OH)Me-(CH2)2CH(Me)(CH2)2-Cl-1742CH(OH)Me-(CH2)2CH(Me)(CH2)2-CN-1743CH(OH)Me-(CH2)2CH(Me)(CH2)2-Me-1744CH(OH)Me iso-PrHH-1745CH(OH)Et iso-PrHCl-1746CH(OH)Et iso-PrHCN-1747CH(OH)Et iso-PrHMe-1748CH(OH)EtCH2CF3 HH-1749CH(OH)EtCH2CF3 HCl-1750CH(OH)EtCH2CF3 HCN-1751CH(OH)EtCH2CF3 HMe-1752CH(OH)EtEtEtH-1753CH(OH)EtEtEtCl-1754CH(OH)EtEtEtCN-1755CH(OH)EtEtEtMe-1756CH(OH)Et-(CH2)2CH(Me)(CH2)2-H-1757CH(OH)Et-(CH2)2CH(Me)(CH2)2-Cl-1758CH(OH)Et-(CH2)2CH(Me)(CH2)2-CN-1759CH(OH)Et-(CH2)2CH(Me)(CH2)2-Me-1760CH(OH)iso-Pr iso-PrHH-1761CH(OH)iso-Pr iso-PrHCl-1762CH(OH)iso-Pr iso-PrHCN-1763CH(OH)iso-Pr iso-PrHMe-1764CH(OH)iso-PrCH2CF3 HH-1765CH(OH)iso-PrCH2CF3 HCl-1766CH(OH)iso-PrCH2CF3 HCN-1767CH(OH)iso-PrCH2CF3 HMe-1768CH(OH)iso-PrEtEtH-1769CH(OH)iso-PrEtEtCl-1770CH(OH)iso-PrEtEtCN-1771CH(OH)iso-PrEtEtMe-1172CH(OH)iso-Pr-(CH2)2CH(Me)(CH2)2-H-1773CH(OH)iso-Pr-(CH2)2CH(Me)(CH2)2-Cl-1774CH(OH)iso-Pr-(CH2)2CH(Me)(CH2)2-CN-1775CH(OH)iso-Pr-(CH2)2CH(Me)(CH2)2-Me-1776CH(OMe)Me iso-PrHH-1777CH(OMe)Me iso-PrHCl-1778CH(OMe)Me iso-PrHCN-
    [0098] [Table 36]Compound NoRR1 R2 XYm1779CH(OMe)Me iso-PrHMe-1780CH(OMe)MeCH3CF3 HH-1781CH(OMe)MeCH3CF3 HCl-1782CH(OMe)MeCH3CF3 HCN-1783CH(OMe)MeCH3CF3 HMe-1784CH(OMe)MeEtEtH-1785CH(OMe)MeEtEtCl-1786CH(OMe)MeEtEtCN-1787CH(OMe)MeEtEtMe-1788CH(OMe)Me-(CH2)2CH(Me)(CH2)2-H-1789CH(OMe)Me-(CH2)2CH(Me)(CH2)2-Cl-1790CH(OMe)Me-(CH2)2CH(Me)(CH2)2-CN-1791CH(OMe)Me-(CH2)2CH(Me)(CH2)2-Me-1792CH(OEt)Me iso-PrHH-1793CH(OEt)Me iso-PrHCl-1794CH(OEt)Me iso-PrHCN-1795CH(OEt)Me iso-PrHMe-1796CH(OEt)MeCH2CF3 HH-1797CH(OEt)MeCH2CF3 HCl-1798CH(OEt)MeCH2CF3 HCN-1799CH(OEt)MeCH2CF3 HMe-1800CH(OEt)MeEtEtH-1801CH(OEt)MeEtEtCl 1802CH(OEt)MeEtEtCN-1803CH(OEt)MeEtEtMe-1804CH(OEt)Me-(CH2)2CH(Me)(CH2)2-H-1805CH(OEt)Me-(CH2)2CH(Me)(CH2)2-Cl-1806CH(OEt)Me-(CH2)2CH(Me)(CH2)2-CN-1807CH(OEt)Me-(CH2)2CH(Me)(CH2)2-Me-1808CH(OMe)Et iso-PrHH-1809CH(OMe)Et iso-PrHCl-1810CH(OMe)Et iso-PrHCN-1811CH(OMe)Et iso-PrHMe-1812CH(OMe)EtCH2CF3 HH-1813CH(OMe)EtCH2CF3 HCl-1814CH(OMe)EtCH2CF3 HCN-1815CH(OMe)EtCH2CF3 HMe-1816CH(OMe)EtEtEtH-1817CH(OMe)EtEtEtCl-1818CH(OMe)EtEtEtCN-1819CH(OMe)EtEtEtMe-1820CH(OMe)Et-(CH2)2CH(Me)(CH2)2-H-1821CH(OMe)Et-(CH2)2CH(Me)(CH2)2-Cl-1822CH(OMe)Et-(CH2)2CH(Me)(CH2)2-CN-1823CH(OMe)Et-(CH2)2CH(Me)(CH2)2-Me-1824O(=O)H iso-PrHH-1825O(=O)H iso-PrHCl-1826O(=O)H iso-PrHCN-1827O(=O)H iso-PrHMe-1828O(=O)HCH2CF3 HH-1829O(=O)HCH2CF3 HCl-
    [0099] [Table 37]Compound NoRR1 R2 XYm1830C(=O)HCH3CF3 HCN-1831C(=O)HCH3CF3 HMe-1632C(=O)HEtEtH-1833C(=O)HEtEtCl-1834C(=O)HEtEtCN-1835C(=O)HEtEtMe-1836C(=O)H-(CH3)3CH(Me)(CH3)3-H-1837C(=O)H-(CH3)3CH(Me)(CH3)3-Cl-1838C(=O)H-(CH3)3CH(Me)(CH3)3-CN-1839C(=O)H-(CH3)3CH(Me)(CH3)3-Me-1840C(=O)Me iso-PrHH-1841C(=O)Me iso-PrHCl-1842C(=O)Me iso-PrHCN-1843C(=O)Me iso-PrHMe-1844C(=O)MeCH3CF3 HH-1845C(=O)MeCH3CF3 HCl-1846C(=O)MeCH3CF3 HCN-1847C(=O)MeCH3CF3 HMe-1848C(=O)MeEtEtH-1849C(=O)MeEtEtCl-1850C(=O)MeEtEtSO3Me-1851C(=O)MeEtEtCN-1852C(=O)MeEtEtMe-1853C(=O)Me-(CH3)3CH(Me)(CH3)3-H-1854C(=O)Me-(CH3)3CH(Me)(CH3)3 Cl-1855C(=O)Me-(CH3)3CH(Me)(CH3)3-CN-1856C(=O)Me(CH3)3CH(Me)(CH3)3-Me-1857C(=O)Et iso-PrHH-1858C(=O)Et iso-PrHCl-1859C(=O)Et iso-PrHCN-1860C(=O)Et iso-PrHMe-1861C(=O)EtCH2CF3 HH-1862C(=O)EtCH2OF3 HCl-1863C(C=O)EtOH2CF3 HCN-1864C(=O)EtCH2CF3 HMe-1865C(=O)EtEtEtH-1866C(=O)EtEtEtCl-1867C(=O)EtEtEtCN-1868C(=O)EtEtEtMe-1869C(=O)Et-(CH3)3CH(Me)(CH3)3-H-1870C(=O)Et-(CH3)3CH(Me)(CH3)3-Cl-1871C(=O)Et-(CH3)3CH(Me)(CH3)3-CN-1872C(=O)Et-(CH3)3CH(Me)(CH3)3-Me-1873C(=O)iso-Pr iso-PrHH-1874C(=O)iso-Pr iso-PrHCl-1875C(=O)iso-Pr iso-PrHCN-1876C(=O)iso-Pr iso-PrHMe-1877C(=O)iso-PrCH2CF3 HH-1878C(=O)iso-PrCH2CF3 HCl-1879C(=O)iso-PrCH3CF3 HCN-1880C(=O)iso-PrCH2CF3 HMe-
    [0100] [Table 381Compound NoRR1 R2 XYm1881C(=O)iso-PrEtEtH-1882C(=O)iso-PrEtEtCl-1883C(=O)iso-PrEtEtCN-1884C(=O)iso-PrEtEtMe-1885C(=O)iso-Pr-(CH3)3CH(Me)(CH3)3-H-1886C(=O)iso-Pr-(CH3)3CH(Me)(CH3)3-Cl-1887C(=O)iso-Pr-(CH3)3CH(Me)(CH3)3 CN-1888C(=O)iso-Pr-(CH3)3CH(Me)(CH3)3-Me-1889CH=CH3 iso-PrHH-1890CH=CH3 iso-PrHCl-1891CH=CH3 iso-PrHCN-1892CH=CH3 iso-PrHMe-1893CH=CH3 CH3CF3 HH-1894CH=CH3 CH3CF3 HCl-1895CH=CH3 CH2CF3 HCN-1896CH=CH3 CH3CF3 HMe-1897CH=CH3 EtEtH-1898CH=CH3 EtEtCl-1899CH=CH3 EtEtCN-1900CH=CH3 EtEtMe-1901CH=CH3 -(CH3)3CH(Me)(CH3)3-H-1902CH=CH3 -(CH3)CH(Me)(CH3)3-Cl-1903CH=CH3 (CH3)3CH(Me)(CH3)3.CN-1904CH=CH3 -(CH3)3CH(Me)(CH3)3-Me-1905CH3CH=CH3 iso-PrHH-1906CH3CH=CH3 iso-PrHCl-1907CH3CH=CH3 iso-PrHCN-1908CH3CH=CH3 iso-PrHMe-1909CH3CH=CH3 CH3CF3 HH-1910CH3CH=CH3 CH3CF3 HCl-1911CH3CH=CH3 CH3GF3 HCN-1912CH3CH=CH3 CH3CF3 HMe-1913CH3CH=CH3 EtEtH-1914CH3CH=CH3 EtEtCl-1915CH3CH=CH3 EtEtCN-1916CH2CH=CH3 EtEtMe-1917CH3CH=CH3 -(CH3)3CH(Me)(CH3)3-H-1918CH3CH=CH3 -(CH3)3CH(Me)(CH3)3-Cl-1919CH3CH=CH3 -(CH3)3CH(Me)(CH3)3-CN-1920CH3CH=CH3 -(CH3)3CH(Me)(CH3)3-Me-1921CH(Me)CH=CH3 iso-PrHH-1922CH(Me)CH=CH3 iso-PrHCl-1923CH(Me)CH=CH3 iso-PrHCN-1924CH(Me)CH=CH3 iso-PrHMe-1925CH(Me)CH=CH3 CH3CF3 HH-1926CH(Me)CH=CH3 CH3CF3 HCl-1927CH(Me)CH=CH3 CH3CF3 HCN-1928CH(Me)CH=CH3 CH3CF3 HMe-1929CH(Me)CH=CH3 EtEtH-1930CH(Me)CH=CH3 EtEtCl-1931CH(Me)CH=CH3 EtEtCN-
    [0101] [Table 39]Compound No.RR1 R2 XYm1932CH(Me)CH=CH3 EtEtMe-1933CH(Me)CH=CH3 -(CH3)3CH(Me)(CH3)3-H-1934CH(Me)CH=CH3 -(CH3)3CH(Me)(CH3)3-Cl-1935CH(Me)CH=CH3 -(CH3)3CH(Me)(CH3)3-CN-1936CH(Me)CH=CH3 -(CH3)3CH(Me)(CH3)3-Me-1937C(Me)=CHMe iso-PrHH-1938C(Me)=CHMe iso-PrHCl-1939C(Me)=CHMe iso-PrHCN-1940C(Me)=CHMe iso-PrHMe-1941C(Me)=CHMeCH2CF3 HH-1942C(Me)=CHMeCH2CF3 HCl-1943C(Me)=CHMeCH2CF3 HCN-1944C(Me)=OHMeCH3CF3 HMe-1945C(Me)=CHMeEtEtH-1946C(Me)=CHMeEtEtCl-1947C(Me)=CHMeEtEtCN-1948C(Me)=CHMeEtEtMe-1949C(Me)=CHMe-(CH3)3CH(Me)(CH3)3-H-1950C(Me)=CHMe-(CH3)3CH(Me)(CH3)3-Cl-1951C(Me)=CHMe-(CH3)3CH(Me)(CH3)3-CN-1962C(Me)=CHMe-(CH3)3CH(Me)(CH3)3-Me-19532-cyclopenten-1-yl iso-PrHH-19542-cyclopenten-1-yl iso-PrHCl-19552-cyclopenten-1-yl iso-PrHCN-19562-cyclopenten-1-yl iso-PrHMe-19572-cyclopenten-1-ylCH2CF3 HH-19582-cyclopenten-1-ylCH2CF3 HCl-19592-cyclopenten-1-ylCH2CF3 HCN-19602-cyclopenten-1-ylCH2CF3 HMe-19612-cyclopenten-1-ylEtEtH-19622-cyclopenten-1-ylEtEtCl-19632-cyclopenten-1-ylEtEtCN-19642-cyclopenten-1-ylEtEtMe-19652-cyclopenten-1-yl-(CH3)3-CH(Me)(CH3)3-H-19662-cyclopenten-1-yl-(CH3)3-CH(Me)(CH3)3-Cl-19672-cyclopenten-1-yl-(CH3)3-CH(Me)(CH3)3-CN-19682-cyclopenten-1-yl-(CH3)3-CH(Me)(CH3)3-Me-19692-cyclopenten-1-yl iso-PrHH-19702-cyclopenten-1-yl iso-PrHCl-19712-cyclopenten-1-yl iso-PrHCN-19722-cyclopenten-1-yl iso-PrHMe-19732-cyclopenten-1-ylCH2CF3 HH-19742-cyclopenten-1-ylCH2CF3 HCl-19752-cyclopenten-1-ylCH2CF3 HCN-19762-cyclopenten-1-ylCH2CF3 HMe-19772-cyclopenten-1-ylEtEtH-19782-cyclopenten-1-ylEtEtCl-19792-cyclopenten-1-ylEtEtCN-19802-cyclopenten-1-ylEtEtMe-19812-cyclopenten-1-yl-(CH3)3CH(Me)(CH3)3-H-19822-cyclopenten-1-yl-(CH3)3CH(Me)(CH3)3-Cl-
    [0102] [Table 40]Compound NoRR1 R2 XYm19832-cyclopenten-1-yl-(CH3)3CH(Me)(CH3)3-CN-19842-cyclopenten-1-yl-(CH3)3CH(Me)(CH3)3-Me-19851,3-dioxolan-2-yl iso-PrHH-19861,3-dioxolan-2-yl iso-PrHCl-19871,3-dioxolan-2-yl iso-PrHCN-19881,3-dioxolan-2-yl iso-PrHMe-19891,3-dioxolan-2-ylCH2CF3 HH-19901,3-dioxolan-2-ylCH2CF3 HCl-19911,3-dioxolan-2-ylCH2CF3 HCN-19921,3-dioxolan-2-ylCH2CF3 HMe-19931,3-dioxolan-2-ylEtEtH-19941,3-dioxolan-2-ylEtEtCl-19951,3-dioxolan-2-ylEtEtSO2Me-19961,3-dioxolan-2-ylEtEtCN-19911,3-dioxolan-2-ylEtEtMe-19981,3-dioxolan-2-yl-(CH3)3CH(Me)(CH3)3-H-19991,3-dioxolan-2-yl-(CH3)3CH(Me)(CH3)3-Cl-20001,3-dioxolan-2-yl-(CH3)3CH(Me)(CH3)3-CN-20011,3-dioxolan-2-yl-(CH3)3CH(Me)(CH3)3-Me-20021,3-dioxan-2-yl iso-PrHH-20031,3-dioxan-2-yl iso-PrHCl-20041,3-dioxan-2-yl iso-PrHCN-20051,3-dioxan-2-yl iso-PrHMe-20061,3-dioxan-2-ylCH2CF3 HH-20071,3-dioxan-2-ylCH2CF3 HCl 20081,3-dioxan-2-ylCH2CF3 HCN-20091,3-dioxan-2-ylCH2CF3 HMe-20101,3-dioxan-2-ylEtEtH-20111,3-dioxan-2-ylEtEtCl-20121,3-dioxan-2-ylEtEtCN-20131,3-dioxan-2-ylEtEtMe-20141,3-dioxan-2-yl-(CH3)3CH(Me)(CH2)3-H-20151,3-dioxan-2-yl-(CH3)3CH(Me)(CH2)3-Cl-20161,3-dioxan-2-yl-(CH3)3CH(Me)(CH2)3-CN-20171,3-dioxan-2-yl-(CH3)3CH(Me)(CH2)3-Me-
    [0103] The compound of the present application represented by Formula [I] can be produced according to Production Methods shown below, but not limited by these methods. The production methods are described in detail for every process. <Production Method 1>(Process 1)
    [0104]
    [0105] (wherein R has the same meaning as defined above and R3s are each a leaving group such as a C1-6 alkyl group, an optionally substituted phenyl group or an optionally substituted benzyl group).
    [0106] The compound represented by Formula [III] can be produced by allowing the compound represented by Formula [II] to react with thiourea in a suitable solvent in the presence of a suitable base.
    [0107] The reaction temperature of the present reaction is in the arbitrarily range of from 0°C to reflux temperature in the reaction system, preferably from 10 to 150°C.
    [0108] The reaction time of the present reaction varies according to a reaction temperature, a reactant, a reaction amount, or the like, but is between 0.5 and 120 hours.
    [0109] For the amount of agents to be provided in the present reaction, 1 to 2 equivalents of the thiourea and 1 to 5 equivalents of the base are used with respect to 1 equivalent of the compound represented by Formula [II]. In addition, the amount of solvent to be used is from 0 to 50 L (liter), preferably from 0.1 to 3.0 L, with respect to 1 mole of the compound represented by Formula [II].
    [0110] The solvent for use in the present process may be any solvent as long as it is an inert solvent not inhibiting the process of the present reaction. Examples thereof may include ethers such as 1,2-dimethoxyethane and tetrahydrofuran; amides such as N,N-dimethylacetoamide, N,N-dimethylformamide, 1,3-dimethyl-2-imidazolidinone and N-methyl-2-pyrrolidinone; sulfur compounds such as dimethylsulfoxide and sulfolane; aromatic hydrocarbons such as benzene, toluene and xylene; alcohols such as methanol, ethanol, propanol, isopropanol, butanol, 2-methoxyethanol and tert-butanol; water; and a mixture thereof.
    [0111] Examples of the base that can be used in the present process may include organic bases such as pyridine, triethylamine, tributylamine and 1,8-diazabicyclo[5.4.0]-7-undecene; inorganic bases such as alkali metal hydroxide, for example, sodium hydroxide or potassium hydroxide, alkaline-earth metal hydroxide, for example, calcium hydroxide or magnesium hydroxide, alkali metal carbonates, for example, sodium carbonate or potassium carbonate, alkali metal acetates, for example, sodium acetate or potassium acetate and alkali metal bicarbonates, for example, sodium bicarbonate or potassium bicarbonate; and alcohol metal salts such as sodium methoxide, sodium ethoxide and potassium tert-butoxide.
    [0112] After completion of the reaction, the compound represented by Formula [III] that is a desired product of the present reaction can be used in the subsequent process without being isolated and purified, but can be collected from the reaction system by a usual method and purified by a manipulation such as column chromatography or recrystallization, as the case requires. (Process 2)
    [0113]
    [0114] (wherein R has the same meaning as defined above, R4 is a C1-6 alkyl group, an optionally substituted phenyl group, or an optionally substituted benzyl group and L is a halogen atom, an optionally substituted alkylsulfonyloxy group, an optionally substituted phenylsulfonyloxy group, or an optionally substituted benzylsulfonyloxy group).
    [0115] The compound represented by Formula [V] can be produced by allowing the compound represented by Formula [III] to react with the compound represented by Formula [IV] in a suitable solvent, in the presence of a suitable base.
    [0116] The reaction temperature of the present reaction is in the arbitrarily range of from 0°C to reflux temperature in the reaction system, preferably from 10 to 150°C.
    [0117] The reaction time of the present reaction varies according to a reaction temperature, a reactant, a reaction amount, or the like, but is between 1 and 72 hours.
    [0118] For the amount of agents to be provided in the present reaction, 1 to 3 equivalents of the compound represented by Formula [IV] and 1 to 3 equivalents of the base are used with respect to 1 equivalent of the compound represented by Formula [III]. In addition, the amount of solvent to be used is from 0 to 50 L, preferably from 0.1 to 3.0 L, with respect to 1 mole of the compound represented by Formula [III].
    [0119] As the solvent and base that can be used in the present process, the same ones mentioned in Process 1 of Production Method 1 can be exemplified.
    [0120] After completion of the reaction, the compound represented by Formula [V] that is a desired product of the present reaction can be collected from the reaction system by a usual method and, as the case requires, purified by a manipulation such as column chromatography or recrystallization. (Process 3)
    [0121]
    [0122] (wherein R and R4 have the same meanings as defined above and X1 is a chlorine atom or a bromine atom).
    [0123] The compound represented by Formula [VIa] can be produced by allowing the compound represented by Formula [V] to react with a halogenating agent in a suitable solvent or in the absence of a solvent. Also, a suitable catalyst can be added for the production.
    [0124] The reaction temperature of the present reaction is in the arbitrarily range of from 0°C to reflux temperature in the reaction system, preferably from 0 to 150°C.
    [0125] The reaction time of the present reaction varies according to a reaction temperature, a reactant, a reaction amount, or the like, but is between 1 and 72 hours.
    [0126] For the amount of agents to be provided in the present reaction, 1 to 5 equivalents of the halogenating agent and 0.01 to 1.0 equivalent of the catalyst are used with respect to 1 equivalent of the compound represented by Formula [V]. In addition, the amount of solvent to be used is from 0 to 50 L, preferably from 0 to 3.0 L, with respect to 1 mole of the compound represented by Formula [V].
    [0127] The solvent for use in the present process may be any solvent as long as it is an inert solvent not inhibiting the process of the present reaction. Examples thereof may include nitriles such as acetonitrile; aromatic hydrocarbons such as toluene and xylene; halogenated hydrocarbons such as monochlorobenzene and 1,2-dichloroethane; and the like.
    [0128] As the halogenating agent that can be used in the present process, phosphorus oxychloride, phosphorus oxybromide, thionyl chloride, thionyl bromide, or the like can be exemplified.
    [0129] As the catalyst that can be used in the present process, triethylamine, N,N-dimethylformamide, N,N-dimethylaniline, N,N-diethylaniline, or the like can be exemplified.
    [0130] After completion of the reaction, the compound represented by Formula [VIa] that is a desired product of the present reaction can be collected from the reaction system by a usual method and, as the case requires, purified by a manipulation such as column chromatography or recrystallization. (Process 4)
    [0131]
    [0132] (wherein R, R1, R2, R4 and X1 have the same meanings as defined above).
    [0133] The compound represented by Formula [VIII] can be produced by allowing the compound represented by Formula [VIa] to react with the compound represented by Formula [VII] in a suitable solvent or in the absence of a solvent, in the presence of a suitable base. Also, a suitable catalyst can be added for the production.
    [0134] The reaction temperature of the present reaction is in the arbitrarily range of from 0°C to reflux temperature in the reaction system, preferably from 0 to 150°C.
    [0135] The reaction time of the present reaction varies according to a reaction temperature, a reactant, a reaction amount, or the like, but is between 1 and 120 hours.
    [0136] For the amount of agents to be provided in the present reaction, 1 to 3, preferably 1 to 1.5 equivalents of the compound represented by Formula [VII], 1 to 3, preferably 1 to 1.5 equivalents of the base and 0.001 to 0.5 equivalent of the catalyst are used, with respect to 1 equivalent of the compound represented by Formula [VIa]. In addition, the amount of solvent to be used is from 0 to 50 L, preferably from 0.1 to 3.0 L, with respect to 1 mole of the compound represented by Formula [VIa].
    [0137] The solvent for use in the present process may be any solvent as long as it is an inert solvent not inhibiting the process of the present reaction. Examples thereof may include ethers such as 1,2-dimethoxyethane and tetrahydrofuran; halogenated hydrocarbons such as dichloroethane, carbon tetrachloride, chlorobenzene and dichlorobenzene; amides such as N,N-dimethylacetoamide, N,N-dimethylformamide, 1,3-dimethyl-2-imidazolidinone and N-methyl-2-pyrrolidinone; sulfur compounds such as dimethylsulfoxide and sulfolane; aromatic hydrocarbons such as benzene, toluene and xylene; alcohols such as methanol, ethanol, n-propanol, 2-propanol, n-butanol and 2-methyl-2-propanol; nitriles such as acetonitrile; carboxylic acids such as formic acid and acetic acid; water; and a mixture thereof.
    [0138] Examples of the base that can be used in the present process may include organic bases such as pyridine, triethylamine, tributylamine and 1,8-diazabicyclo[5.4.0]-7-undecene; inorganic bases such as alkali metal hydroxide, for example, sodium hydroxide or potassium hydroxide, alkaline-earth metal hydroxide, for example, calcium hydroxide or magnesium hydroxide, alkali metal carbonates, for example, sodium carbonate or potassium carbonate and alkali metal bicarbonates, for example, sodium bicarbonate or potassium bicarbonate; alcohol metal salts such as sodium methoxide, sodium ethoxide and potassium tert-butoxide; and alkali metal hydrides such as sodium hydride.
    [0139] As the catalyst that can be used in the present process, for example, sodium p-toluenesulfinate, sodium methane-sulfinate, or sodium benzenesulfinate can be exemplified.
    [0140] After completion of the reaction, the compound represented by Formula [VIII] that is a desired product of the present reaction can be collected from the reaction system by a usual method and, as the case requires, purified by a manipulation such as column chromatography or recrystallization.
    [0141] Further, in place of the compounds represented by Formulae [VIa] and [VIII], a compound in which any one of X1 is X (X has the same meaning as defined above, but is an atom other than a chlorine atom and a bromine atom) can also be used as a raw material as in the present process and can be produced. (Process 5)
    [0142]
    [0143] (wherein R, R1, R4 and X1 have the same meanings as defined above and R5 is a C1-6 alkyl group, a C1-6 haloalkyl group, or a C1-6 alkykoxy group).
    [0144] The compound represented by Formula [X] can be produced by hydrolyzing the compound represented by Formula [IX] in a suitable solvent or in the absence of a solvent with the use of acid or base.
    [0145] The reaction temperature of the present reaction is in the arbitrarily range of from 0°C to reflux temperature in the reaction system, preferably from 0 to 150°C.
    [0146] The reaction time of the present reaction varies according to a reaction temperature, a reactant, a reaction amount, or the like, but is between 1 and 120 hours.
    [0147] For the amount of agent to be provided in the present reaction, 1 to 10, preferably 1 to 3 equivalents of acid or base can be used with respect to 1 equivalent of the compound represented by Formula [IX]. An amount of the solvent to be used is from 0 to 50 L, preferably from 0.1 to 3.0 L, with respect to 1 mole of the compound represented by Formula [IX].
    [0148] The solvent for use in the present process may be any solvent as long as it is an inert solvent not inhibiting the process of the present reaction. Examples thereof may include ethers such as 1,2-dimethoxyethane and tetrahydrofuran; halogenated hydrocarbons such as dichloroethane, carbon tetrachloride, chlorobenzene and dichlorobenzene; amides such as N,N-dimethylacetoamide, N,N-dimethylformamide, 1,3-dimethyl-2-imidazolidinone and N-methyl-2-pyrrolidinone; sulfur compounds such as dimethylsulfoxide and sulfolane; aromatic hydrocarbons such as benzene, toluene and xylene; alcohols such as methanol, ethanol, n-propanol, 2-propanol, n-butanol and 2-methyl-2-propanol; nitrites such as acetonitrile; carboxylic acids such as formic acid and acetic acid; water; and a mixture thereof.
    [0149] As the acid that can be used in the present process, inorganic acids such as hydrochloric acid, sulfuric acid, phosphoric acid, or nitric acid; organic acids such as formic acid, acetic acid, trifluoroacetic acid, methanesulfonic acid, tartaric acid, citric acid, or succinic acid; or a mixture thereof can be exemplified.
    [0150] Examples of the base that can be used in the present process may include organic bases such as pyridine, triethylamine, tributylamine and 1,8-diazabicyclo[5.4.0]-7-undecene; inorganic bases such as alkali metal hydroxide, for example, sodium hydroxide or potassium hydroxide, alkaline-earth metal hydroxide, for example, calcium hydroxide or magnesium hydroxide, alkali metal carbonates, for example, sodium carbonate or potassium carbonate and alkali metal bicarbonates, for example, sodium bicarbonate or potassium bicarbonate; alcohol metal salts such as sodium methoxide, sodium ethoxide and potassium tert-butoxide; and alkali metal hydrides such as sodium hydride.
    [0151] After completion of the reaction, the compound represented by Formula [X] that is a desired product of the present reaction can be collected from the reaction system by a usual method and, as the case requires, purified by a manipulation such as column chromatography or recrystallization.
    [0152] Further, in place of the compounds represented by Formulae [IX] and [X], a compound in which X1 is X (X has the same meaning as defined above, but is an atom other than a chlorine atom and a bromine atom) can also be used as a raw material as in the present process and can be produced. (Process 6)
    [0153]
    [0154] (wherein R, R1, R2, R4 and X1 have the same meanings as defined above).
    [0155] The compound represented by Formula [XI] can be produced by allowing the compound represented by Formula [VIII] to react with an oxidizing agent in a suitable solvent. Also, a suitable catalyst can be added for the production.
    [0156] The reaction temperature of the present reaction is in the arbitrarily range of from -30°C to reflux temperature in the reaction system, preferably from 0 to 100°C.
    [0157] The reaction time of the present reaction varies according to a reaction temperature, a reactant, a reaction amount, or the like, but is between 0.5 and 48 hours.
    [0158] For the amount of agents to be provided in the present reaction, 0.5 to 5 equivalents of an oxidizing agent and 0.01 to 0.5 equivalent of the catalyst are used, with respect to 1 equivalent of the compound represented by Formula [VIII]. In addition, the amount of solvent to be used is from 0 to 50 L, preferably from 0.1 to 3.0 L, with respect to 1 mole of the compound represented by Formula [VIII].
    [0159] The solvent for use in the present process may be any solvent as long as it is an inert solvent not inhibiting the process of the present reaction. Examples thereof may include halogenated hydrocarbons such as dichloromethane, chloroform, 1,2-dichloroethane, carbon tetrachloride, chlorobenzene and dichlorobenzene; alcohols such as methanol, ethanol, propanol, isopropanol, butanol and tert-butanol; ketones such as acetone and 2-butanone; nitriles such as acetonitrile; acetic acid; water; and a mixture thereof.
    [0160] Examples of the oxidizing agent that can be used in the present process may include organic peroxides such as m-chloroperbenzoate, peroxyformic acid and peracetic acid; and inorganic peroxides such as OXONE (trade name, produced by Du Pont, 2KHSO5·KHSO4·K2SO4), hydrogen peroxide, potassium permanganate and sodium periodate.
    [0161] As the catalyst that can be used in the present process, for example, sodium tungstate can be exemplified.
    [0162] After completion of the reaction, the compound represented by Formula [XI] that is a desired product of the present reaction can be collected from the reaction system by a usual method and, as the case requires, purified by a manipulation such as column chromatography or recrystallization.
    [0163] Further, in place of the compounds represented by Formulae [VIII] and [XI], a compound in which X1 is X (X has the same meaning as defined above, but is an atom other than a chlorine atom and a bromine atom) can also be used as a raw material as in the present process and can be produced. (Process 7)
    [0164]
    [0165] (wherein R, R1, R2, R4, X1, Y and m have the same meanings as defined above).
    [0166] The compound represented by Formula [XIII] can be produced by allowing the compound represented by Formula [XI] to react with the compound represented by Formula [XII] in a suitable solvent in the presence of a suitable base.
    [0167] The reaction temperature of the present reaction is in the arbitrarily range of from -30°C to reflux temperature in the reaction system, preferably from 0 to 150°C.
    [0168] The reaction time of the present reaction varies according to a reaction temperature, a reactant, a reaction amount, or the like, but is between 0.5 and 48 hours.
    [0169] For the amount of agents to be provided in the present reaction, 1 to 3 equivalents of the compound represented by Formula [XII] and 1 to 3 equivalents of the base are used, with respect to 1 equivalent of the compound represented by Formula [XI]. In addition, the amount of solvent to be used is from 0 to 50 L, preferably from 0.1 to 3.0 L, with respect to 1 mole of the compound represented by Formula [XI].
    [0170] As the solvent and the base that can be used in the present process, the same ones mentioned in Process 4 of Production Method 1 can be exemplified.
    [0171] After completion of the reaction, the compound represented by Formula [XIII] that is a desired product of the present reaction can be collected from the reaction system by a usual method and, as the case requires, purified by a manipulation such as column chromatography or recrystallization.
    [0172] Further, in place of the compounds represented by Formulae [XI] and [XIII], a compound in which X1 is X (X has the same meaning as defined above, but is an atom other than a chlorine atom and a bromine atom) can also be used as a raw material as in the present process or can be produced. <Production Method 2>(Process 8)
    [0173]
    [0174] (wherein R, R1, R2, X1, Y and m have the same meanings as defined above).
    [0175] The compound represented by Formula [XIV] can be produced by reducing the compound represented by Formula [XIII] in a suitable solvent in the presence of a suitable base.
    [0176] As the reduction reaction, for example, a catalytic reduction method which employs the use of hydrogen gas and a suitable catalyst can be mentioned. This catalytic reduction method can be carried out in a hydrogen atmosphere under any conditions of normal pressure and applying pressure.
    [0177] For the amount of agents to be provided in the present reaction, 0.001 to 0.5 equivalent of the catalyst and 0.1 to 5.0 equivalent of the base are used, with respect to 1 equivalent of the compound represented by Formula [XIII]. In addition, the amount of solvent to be used is from 0 to 50 L, preferably from 0.1 to 3.0 L, with respect to 1 mole of the compound represented by Formula [XIII].
    [0178] The reaction temperature of the present reaction is in the arbitrarily range of from 0°C to reflux temperature in the reaction system, preferably from 0 to 100°C.
    [0179] The reaction time of the present reaction varies according to a reaction temperature, a reactant, a reaction amount, or the like, but is between 0.5 and 72 hours.
    [0180] The solvent for use in the present process may be any solvent as long as it is an inert solvent not inhibiting the process of the present reaction. Examples thereof may include aromatic hydrocarbons such as toluene and xylene; halogenated aliphatic hydrocarbons such as dichloromethane and chloroform; acetic acid esters such as methyl acetate, ethyl acetate and butyl acetate; aprotic polar solvents such as N,N-dimethylformamide, N,N-dimethylacetoamide, N-methylpyrrolidone, tetramethyl urea and hexamethylphosphoric triamide; ether-type solvents such as diethylether, tetrahydrofuran and dioxane; aliphatic hydrocarbons such as pentane and n-hexane; fatty alcohols such as methanol, ethanol, n-propanol, isopropanol, 1-butanol, sec-butanol and tert-butanol; water; and the like. Preferred are fatty alcohols such as methanol, ethanol, n-propanol, isopropanol, n-butanol, sec-butanol and tert-butanol and water.
    [0181] As the catalyst that can be used in the present process, platinum, Raney nickel, platinum black, palladium-carbon, ruthenium complex, or the like can be exemplified.
    [0182] Examples of the base that can be used in the present process may include organic bases such as pyridine, triethylamine, tributylamine and 1,8-diazabicyclo[5.4.0]-7-undecene; inorganic bases such as alkali metal hydroxide, for example, sodium hydroxide or potassium hydroxide, alkaline-earth metal hydroxide, for example, calcium hydroxide or magnesium hydroxide, alkali metal carbonates, for examples, sodium carbonate or potassium carbonate, alkali metal acetates, for example, sodium acetate or potassium acetate and alkali metal bicarbonates, for example, sodium bicarbonate or potassium bicarbonate; and alcohol metal salts such as sodium methoxide, sodium ethoxide and potassium tert-butoxide.
    [0183] After completion of the reaction, the compound represented by Formula [XIV] that is a desired product of the present reaction can be collected from the reaction system by a usual method and, as the case requires, purified by a manipulation such as column chromatography or recrystallization. <Production Method 3>(Process 9)
    [0184]
    [0185] (wherein R, R1, R2, Y and m have the same meanings as defined above; X2 is a halogen atom, a C1-6 alkylsulfonyl group, a C1-6 haloalkylsulfonyl group, an optionally substituted benzenesulfonyl group, or an optionally substituted benzylsulfonyl group; and X3 is a C1-6 alkoxy group, a C1-3 haloalkoxy group, a C1-6 alkynyloxy group, a C2-6 alkenyloxy group, a C3-8 cycloalkyloxy group, a C3-8 cycloalkyl C1-3 alkyloxy group, a C1-6 alkylthio group, an optionally substituted phenylthio group, an optionally substituted benzylthio group, an amino- group, a hydroxyl group, an optionally substituted benzyloxy group, a mono C1-6 alkylamino group, or a di(C1-6 alkyl) amino group).
    [0186] The compound represented by Formula [XVII] can be produced by allowing the compound represented by Formula [XV] to react with the compound represented by Formula [XVI] in a suitable solvent in the presence of a suitable base. Also, a suitable catalyst can be added for the production. Among compounds represented by Formula [XV], compounds in which X2 is other than halogen can be produced according to Processes 13, 14 and 15 of Production Method 6 shown below.
    [0187] The reaction temperature of the present reaction is in the arbitrarily range of from -30°C to reflux temperature in the reaction system, preferably from 0 to 150°C.
    [0188] The reaction time of the present reaction varies according to a reaction temperature, a reactant, a reaction amount, or the like, but is between 1 and 120 hours.
    [0189] For the amount of agents to be provided in the present reaction, 1 to 3 equivalents of the compound represented by Formula [XVI] and 1 to 3 equivalents of the base are used, with respect to 1 equivalent of the compound represented by Formula [XV]. In addition, the amount of solvent to be used is from 0 to 50 L, preferably from 0.1 to 3.0 L, with respect to 1 mole of the compound represented by Formula [XV].
    [0190] The solvent for use in the present process may be any solvent as long as it is an inert solvent not inhibiting the process of the present reaction. Examples thereof may include ethers such as 1,2-dimethoxyethane and tetrahydrofuran; halogenated hydrocarbons such as dichloroethane, carbon tetrachloride, chlorobenzene and dichlorobenzene; amides such as N,N-dimethylacetoamide, N,N-dimethylformamide, 1,3-dimethyl-2-imidazoladinane and N-methyl-2-pyrrolidinone; sulfur compounds such as dimethylsulfoxide and sulfolane; aromatic hydrocarbons such as benzene, toluene and xylene; alcohols such as methanol, ethanol, n-propanol, 2-propanol, n-butanol and 2-methyl-2-propanol; nitriles such as acetonitrile; carboxylic acids such as formic acid and acetic acid; water; and a mixture thereof.
    [0191] Examples of the base that can be used in the present process may include organic bases such as pyridine, triethylamine, tributylamine and 1,8-diazabicyclo[5.4.0]-7-undecene; inorganic bases such as alkali metal hydroxide, for example, sodium hydroxide or potassium hydroxide, alkaline-earth metal hydroxide, for example, calcium hydroxide or magnesium hydroxide, alkali metal carbonates, for example, sodium carbonate or potassium carbonate and alkali metal bicarbonates, for example, sodium bicarbonate or potassium bicarbonate; alcohol metal salts such as sodium methoxide, sodium ethoxide and potassium tert-butoxide; and alkali metal hydrides such as sodium hydride.
    [0192] As the catalyst that can be used in the present process, for example, sodium p-toluenesulfinate, sodium methane-sulfinate, or sodium benzenesulfinate can be exemplified.
    [0193] After completion of the reaction, the compound represented by Formula [XVII] that is a desired product of the present reaction can be collected from the reaction system by a usual method and, as the case requires, purified by a manipulation such as column chromatography or recrystallization. <Production Method 4>(Process 10)
    [0194]
    [0195] (wherein R, R1, R2, X2, Y and m have the same meanings as defined above).
    [0196] The compound represented by Formula [XIX] can be produced by allowing the compound represented by Formula [XV] to react with a cyanating agent [XVIII] in a suitable solvent.
    [0197] The reaction temperature of the present reaction is in the arbitrarily range of from -30°C to reflux temperature in the reaction system, preferably from 0 to 150°C.
    [0198] The reaction time of the present reaction varies according to a reaction temperature, a reactant, a reaction amount, or the like, but is between 1 and 120 hours.
    [0199] For the amount of agent to be provided in the present reaction, 1 to 3 equivalents of the compound represented by Formula [XVIII] is used with respect to 1 equivalent of the compound represented by Formula [XV]. In addition, the amount of solvent to be used is from 0 to 50 L, preferably from 0.1 to 3.0 L, with respect to 1 mole of the compound represented by Formula [XV].
    [0200] The solvent for use in the present process may be any solvent as long as it is an inert solvent not inhibiting the process of the present reaction. Examples thereof may include ethers such as 1,2-dimethoxyethane and tetrahydrofuran; halogenated hydrocarbons such as dichloroethane, carbon tetrachloride, chlorobenzene and dichlorobenzene; amides such as N,N-dimethylacetoamide, N,N-dimethylformamide, 1,3-dimethyl-2-imidazolidinone and N-methyl-2-pyrrolidinone; sulfur compounds such as dimethylsulfoxide and sulfolane; aromatic hydrocarbons such as benzene, toluene and xylene; alcohols such as methanol, ethanol, n-propanol, 2-propanol, n-butanol and 2-methyl-2-propanol; nitriles such as acetonitrile; carboxylic acids such as formic acid and acetic acid; water; and a mixture thereof.
    [0201] Examples of the cyanating agent [XVIII] that can be used in the present process may include sodium cyanide, potassium cyanide, zinc cyanide and copper cyanide.
    [0202] After completion of the reaction, the compound represented by Formula [XIX] that is a desired product of the present reaction can be collected from the reaction system by a usual method and, as the case requires, purified by a manipulation such as column chromatography or recrystallization. <Production Method 5>
    [0203]
    [0204] (wherein R, R1, R2, X2, Y and m have the same meanings as defined above and R6 is a C1-6 alkyl group). (Process 11)
    [0205] The compound represented by Formula [XXI] can be produced by allowing the compound represented by Formula [XV] to react with the compound represented by Formula [XX] in a suitable solvent in the presence of a suitable base.
    [0206] The reaction temperature of the present reaction is in the arbitrarily range of from -30°C to reflux temperature in the reaction system, preferably from 0 to 150°C.
    [0207] The reaction time of the present reaction varies according to a reaction temperature, a reactant, a reaction amount, or the like, but is between 1 and 120 hours.
    [0208] For the amount of agents to be provided in the present reaction, 1 to 3 equivalents of the compound represented by Formula [XX] and 1 to 3 equivalents of the base are used, with respect to 1 equivalent of the compound represented by Formula [XV]. In addition, the amount of solvent to be used is from 0 to 50 L, preferably from 0.1 to 3.0 L, with respect to 1 mole of the compound represented by Formula [XV].
    [0209] The solvent for use in the present process may be any solvent as long as it is an inert solvent not inhibiting the process of the present reaction. Examples thereof may include ethers such as 1,2-dimethoxyethane and tetrahydrofuran; halogenated hydrocarbons such as dichloroethane, carbon tetrachloride, chlorobenzene and dichlorobenzene; amides such as N,N-dimethylacetoamide, N,N-dimethylformamide, 1,3-dimethyl-2-imidazolidinone and N-methyl-2-pyrrolidinone; sulfur compounds such as dimethylsulfoxide and sulfolane; aromatic hydrocarbons such as benzene, toluene and xylene; alcohols such as methanol, ethanol, n-propanol, 2-propanol, n-butanol and 2-methyl-2-propanol; nitriles such as acetonitrile; carboxylic acids such as formic acid and acetic acid; water; and a mixture thereof.
    [0210] Examples of the base that can be used in the present process may include organic bases such as pyridine, triethylamine, tributylamine and 1,8-diazabicyclo[5.4.0]-7-undecene; inorganic bases such as alkali metal hydroxide, for example, sodium hydroxide or potassium hydroxide, alkaline-earth metal hydroxide, for example, calcium hydroxide or magnesium hydroxide, alkali metal carbonates, for example, sodium carbonate or potassium carbonate and alkali metal bicarbonates, for example, sodium bicarbonate or potassium bicarbonate; alcohol metal salts such as sodium methoxide, sodium ethoxide and potassium tert-butoxide; and alkali metal hydrides such as sodium hydride.
    [0211] After completion of the reaction, the compound represented by Formula [XXI] that is a desired product of the present reaction can be collected from the reaction system by a usual method and, as the case requires, purified by a manipulation such as column chromatography or recrystallization. (Process 12)
    [0212] The compound represented by Formula [XXII] can be produced by applying the compound represented by Formula [XXI] to a decarboxylation reaction in a suitable solvent or in the absence of a solvent, in the presence of a suitable acid.
    [0213] The reaction temperature of the present reaction is in the arbitrarily range of from 0°C to reflux temperature in the reaction system, preferably from 0 to 150°C.
    [0214] The reaction time of the present reaction varies according to a reaction temperature, a reactant, a reaction amount, or the like, but is between 1 and 120 hours.
    [0215] For the amount of agent to be provided in the present reaction, 0.1 to 10 equivalents of acid is used with respect to 1 equivalent of the compound represented by Formula [XXI]. In addition, the amount of solvent to be used is from 0 to 50 L, preferably from 0.1 to 3.0 L, with respect to 1 mole of the compound represented by Formula [XXI].
    [0216] The solvent for use in the present process may be any solvent as long as it is an inert solvent not inhibiting the process of the present reaction. Examples thereof may include aliphatic hydrocarbons such as pentane, hexane, cyclohexane and petroleum ether; aromatic hydrocarbons such as toluene and xylene; halogenated hydrocarbons such as methylene chloride, chloroform and chlorobenzene; ethers such as diethylether, diisopropylether, tert-butylmethylether, dioxane, anisole and tetrahydrofuran; nitriles such as acetonitrile and propionitrile; ketones such as acetone, methyl ethyl ketone, diethyl ketone and tert-butyl methyl ketone; alcohols such as methanol, ethanol, 1-propanol, 2-propanol, 1-butanol and tert-butanol; amides such as N,N-dimethylacetoamide, N,N-dimethylformamide, 1,3-dimethyl-2-imidazolidinone and N-methyl-2-pyrrolidinone; sulfur compounds such as dimethylsulfoxide and sulfolane; carboxylic acids such as formic acid and acetic acid; water; and a mixture thereof.
    [0217] Examples of the acid that can be used in the present process may include hydrochloric acid, sulfuric acid, phosphoric acid, formic acid, acetic acid, methanesulfonic acid, benzenesulfonic acid and p-toluenesulfonic acid.
    [0218] After completion of the reaction, the compound represented by Formula [XXII] that is a desired product of the present reaction can be collected from the reaction system by a usual method and, as the case requires, purified by a manipulation such as column chromatography or recrystallization. <Production Method 6>
    [0219]
    [0220] (wherein R, R1, R2, Y and m have the same meanings as defined above and R7 is a C1-6 alkyl group, a C1-6 haloalkyl group, an optionally substituted phenyl group, or an optionally substituted benzyl group). (Process 13)
    [0221] The compound represented by Formula [XXIV] can be produced by allowing the compound represented by Formula [XXIII] to react with an oxidizing agent in a suitable solvent. Also, a suitable catalyst can be added for the production. Herein, the compound represented by Formula [XXIII] can be produced by allowing a compound in which X2 in Formula [XV] is a halogen atom to react with a thiol compound R7-SH, in accordance with Process 9 of Production Method 3.
    [0222] The reaction temperature of the present reaction is in the arbitrarily range of from 0°C to reflux temperature in the reaction system, preferably from 10 to 100°C.
    [0223] The reaction time of the present reaction varies according to a reaction temperature, a reactant, a reaction amount, or the like, but is between 0.5 and 48 hours.
    [0224] For the amount of agents to be provided in the present reaction, 0.5 to 5 equivalents of the oxidizing agent and 0.01 to 0.5 equivalent of the catalyst are used, with respect to 1 equivalent of the compound represented by Formula [XXIII]. In addition, the amount of solvent to be used is from 0 to 50 L, preferably from 0.1 to 3.0 L, with respect to 1 mole of the compound represented by Formula [XXIII].
    [0225] As the solvent, the oxidizing agent, the base and the catalyst, for use in the present process, the same ones mentioned in Process 6 of Production Method 1 can be exemplified.
    [0226] After completion of the reaction, the compound represented by Formula [XXIV] that is a desired product of the present reaction can be collected from the reaction system by a usual method and, as the case requires, purified by a manipulation such as column chromatography or recrystallization. (Process 14)
    [0227] The compound represented by Formula [XXV] can be produced by allowing the compound represented by Formula [XXIV] to react with an oxidizing agent in a suitable solvent. Also, a suitable catalyst can be added for the production.
    [0228] The reaction temperature of the present reaction is in the arbitrarily range of from 0°C to reflux temperature in the reaction system, preferably from 10 to 100°C.
    [0229] The reaction time of the present reaction varies according to a reaction temperature, a reactant, a reaction amount, or the like, but is between 0.5 and 48 hours.
    [0230] For the amount of agents to be provided in the present reaction, 0.5 to 5 equivalents of the oxidizing agent and 0.01 to 0.5 equivalent of the catalyst are used, with respect to 1 equivalent of the compound represented by Formula [XXIV]. In addition, the amount of solvent to be used is from 0 to 50 L, preferably from 0.1 to 3.0 L, with respect to 1 mole of the compound represented by Formula [XXIV].
    [0231] As the solvent, the oxidizing agent, the base and the catalyst, for use in the present process, the same ones mentioned in Process 6 of Production Method 1 can be exemplified.
    [0232] After completion of the reaction, the compound represented by Formula [XXV] that is a desired product of the present reaction can be collected from the reaction system by a usual method and, as the case requires, purified by a manipulation such as column chromatography or recrystallization. (Process 15)
    [0233] The compound represented by Formula [XXV] can be produced without obtaining the compound represented by Formula [XXIV] by allowing the compound represented by Formula [XXIII] to react with an oxidizing agent in a suitable solvent. Also, a suitable catalyst can be added for the production.
    [0234] The reaction temperature of the present reaction is in the arbitrarily range of from 0°C to reflux temperature in the reaction system, preferably from 10 to 100°C.
    [0235] The reaction time of the present reaction varies according to a reaction temperature, a reactant, a reaction amount, or the like, but is between 0.5 and 48 hours.
    [0236] For the amount of agents to be provided in the present reaction, 0.5 to 5 equivalents of the oxidizing agent and 0.01 to 0.5 equivalent of the catalyst are used, with respect to 1 equivalent weight of the compound represented by Formula [XXIII]. In addition, the amount of solvent to be used is from 0 to 50 L, preferably from 0.1 to 3.0 L, with respect to 1 mole of the compound represented by Formula [XXIII].
    [0237] As the solvent, the oxidizing agent, the base and the catalyst, for use in the present process, the same ones mentioned in Process 6 of Production Method 1 can be exemplified.
    [0238] After completion of the reaction, the compound represented by Formula [XXV] that is a desired product of the present reaction can be collected from the reaction system by a usual method and, as the case requires, purified by a manipulation such as column chromatography or recrystallization. <Production Method 7>(Process 16)
    [0239]
    [0240] (wherein R, R4, X and X1 have the same meanings as defined above).
    [0241] The compound represented by Formula [XXVI] can be produced by allowing the compound represented by Formula [VI] to react with an oxidizing agent in a suitable solvent. Also, a suitable catalyst can be added for the production.
    [0242] The reaction temperature of the present reaction is in the arbitrarily range of from -100°C to reflux temperature in the reaction system, preferably from -10 to 100°C.
    [0243] The reaction time of the present reaction varies according to a reaction temperature, a reactant, a reaction amount, or the like, but is between 0.5 and 48 hours.
    [0244] For the amount of agents to be provided in the present reaction, 0.5 to 5 equivalents of the oxidizing agent and 0.01 to 0.5 equivalent of the catalyst are used, with respect to 1 equivalent of the compound represented by Formula [VI]. In addition, the amount of solvent to be used is from 0.01 to 50 L, preferably from 0.1 to 3.0 L, with respect to 1 mole of the compound represented by Formula [VI].
    [0245] As the solvent, the oxidizing agent, the base and the catalyst, for use in the present process, the same ones mentioned in Process 6 of Production Method 1 can be exemplified.
    [0246] After completion of the reaction, the compound represented by Formula [XXVI] that is a desired product of the present reaction can be collected from the reaction system by a usual method and, as the case requires, purified by a manipulation such as column chromatography or recrystallization. (Process 17)
    [0247]
    [0248] (wherein R, R4, X, X1, Y and m have the same meanings as defined above)
    [0249] The compound represented by Formula [XXVII] can be produced by allowing the compound represented by Formula [XXVI] to react with the compound represented by Formula [XII] in a suitable solvent, in the presence of a suitable base.
    [0250] The reaction temperature of the present reaction is in the arbitrarily range of from -100°C to reflux temperature in the reaction system, preferably from -78 to 50°C.
    [0251] The reaction time of the present reaction varies according to a reaction temperature, a reactant, a reaction amount, or the like, but is between 0.5 and 48 hours.
    [0252] For the amount of agents to be provided in the present reaction, 1 to 3 equivalents of the compound represented by Formula [XII] and 1 to 3 equivalents of the base are used, with respect to 1 equivalent of the compound represented by Formula [XXVI]. In addition, the amount of solvent to be used is from 0.01 to 50 L, preferably from 0.1 to 3.0 L, with respect to 1 mole of the compound represented by Formula [XXVI].
    [0253] As the solvent and the base for use in the present process, the same ones mentioned in Process 4 of Production Method 1 can be exemplified.
    [0254] After completion of the reaction, the compound represented by Formula [XXVII] that is a desired product of the present reaction can be collected from the reaction system by a usual method and, as the case requires, purified by a manipulation such as column chromatography or recrystallization. (Process 18)
    [0255]
    [0256] (wherein R, R1, R2, X, X1, Y and m have the same meanings as defined above).
    [0257] The compound represented by Formula [I] can be produced by allowing the compound represented by Formula [XXVII] to react with the compound represented by Formula [VII] in a suitable solvent or in the absence of a solvent, in the presence of a suitable base or absence of a base. Also, a suitable catalyst can be added for the production.
    [0258] The reaction temperature of the present reaction is in the arbitrarily range of from 0°C to reflux temperature in the reaction system, preferably from 0 to 150°C.
    [0259] The reaction time of the present reaction varies according to a reaction temperature, a reactant, a reaction amount, or the like, but is between 1 and 120 hours.
    [0260] For the amount of agents to be provided in the present reaction, 1 to 3, preferably 1 to 1.5 equivalents of the compound represented by Formula [VII]; 0 to 3, preferably 1 to 1.5 equivalents of the base; and 0.001 to 0.5 equivalent of the catalyst are used, with respect to 1 equivalent of the compound represented by Formula [XXVII]. In addition, the amount of solvent to be used is from 0 to 50 L, preferably from 0.1 to 3.0 L, with respect to 1 mole of the compound represented by Formula [XXVII].
    [0261] As the solvent, the base and the catalyst for use in the present process, the same ones mentioned in Process 4 of Production Method 1 can be exemplified.
    [0262] After completion of the reaction, the compound represented by Formula [I] that is a desired product of the present reaction can be collected from the reaction system by a usual method and, as the case requires, purified by a manipulation such as column chromatography or recrystallization. <Production Method 8>(Process 19)
    [0263]
    [0264] (wherein R, R1, R2, X1, Y and m have the same meanings as defined above).
    [0265] The compound represented by Formula [XXVIII] can be produced by fluorinating the compound represented by Formula [XIII] with a fluorinating agent in a suitable solvent or in the absence of a solvent.
    [0266] The reaction temperature of the present reaction is in the arbitrarily range of from 0°C to reflux temperature in the reaction system, preferably from 0 to 150°C.
    [0267] The reaction time of the present reaction varies according to a reaction temperature, a reactant, a reaction amount, or the like, but is between 1 and 120 hours.
    [0268] For the amount of agent to be provided in the present reaction, 1 to 20, preferably 1 to 5 equivalents of the fluorinating agent is used with respect to 1 equivalent of the compound represented by Formula [XIII]. In addition, the amount of solvent to be used is from 0 to 50 L, preferably from 0.1 to 3.0 L, with respect to 1 mole of the compound represented by Formula [XIII].
    [0269] As the solvent that can be used in the present process, the same solvent mentioned in Process 4 of Production Method 1 can be exemplified.
    [0270] As the fluorinating agent that can be used in the present process, potassium fluoride, sodium fluoride, cesium fluoride, or a mixture thereof can be exemplified.
    [0271] After completion of the reaction, the compound represented by Formula [XXVIII] that is a desired product of the present reaction can be collected from the reaction system by a usual method and, as the case requires, purified by a manipulation such as column chromatography or recrystallization. <Production Method 9>(Process 20)
    [0272]
    [0273] (wherein R, R1, R2, R4 and X have the same meanings as defined above and n is an integer of 0 to 2).
    [0274] The compound represented by Formula [XXX] can be produced by allowing the compound represented by Formula [XXIX] to react with hydrazine in a suitable solvent or in the absence of a solvent, in the presence or absence of a base.
    [0275] The reaction temperature of the present reaction is in the arbitrarily range of from 0°C to reflux temperature in the reaction system, preferably from 0 to 150°C.
    [0276] The reaction time of the present reaction varies according to a reaction temperature, a reactant, a reaction amount, or the like, but is between 1 and 120 hours.
    [0277] For the amount of agents to be provided in the present reaction, 1 to 20, preferably 1 to 5 equivalents of hydrazine; and 0 to 3, preferably 0 to 1.5 equivalents of the base are used, with respect to 1 equivalent of the compound represented by Formula [XXIX]. In addition, the amount of solvent to be used is from 0 to 50 L, preferably from 0.1 to 3.0 L, with respect to 1 mole of the compound represented by Formula [XXIX].
    [0278] As the solvent and the base for use in the present process, the same ones mentioned in Process 4 of Production Method 1 can be exemplified.
    [0279] After completion of the reaction, the compound represented by Formula [XXX] that is a desired product of the present reaction can be collected from the reaction system by a usual method and, as the case requires, purified by a manipulation such as column chromatography or recrystallization. (Process 21)
    [0280]
    [0281] (wherein R, R1, R2, X, Y and m have the same meanings as defined above; R8, R9, R12 and R13 are each independently a halogen atom, a cyano group, a C1-6 alkylthio group, a C1-6 acyl group, a C1-6 haloalkylcarbonyl group, a C3-8 cycloalkylcarbonyl group, a carboxyl group, a C1-6 alkoxycarbonyl group or a carbamoyl group; R10 is a hydrogen atom, a halogen atom, a C1-6 alkyl group, a C1-6 haloalkyl group, a C3-8 cycloalkyl group, a C1-6 alkoxy group, a C1-6 acryl group, an amino group, a nitro group, a cyano group, a hydroxyl group or a C1-6 alkoxycarbonyl group; and R11 and R14 are each independently a hydrogen atom, a C1-6 alkylthio group, a di(C1-6 alkyl)amino group or a C1-6 alkoxy group).
    [0282] The compound represented by Formula [I] can be produced by allowing the compound represented by Formula [XXX] to react with the compound represented by Formula [XXXI-1] or [XXXI-2] in a suitable solvent or in the absence of a solvent, in the presence or absence of acid or base.
    [0283] The reaction temperature of the present reaction is in the arbitrarily range of from 0°C to reflux temperature in the reaction system, preferably from 0 to 150°C.
    [0284] The reaction time of the present reaction varies according to a reaction temperature, a reactant, a reaction amount or the like, but is between 1 and 120 hours.
    [0285] For the amount of agents to be provided in the present reaction, 1 to 10, preferably 1 to 3 equivalents of the compound represented by Formula [XXXI-1] or [XXXI-2]; and 0 to 5, preferably 0 to 3 equivalents of acid or base are used, with respect to 1 equivalent of the compound represented by Formula [XXX]. In addition, the amount of solvent to be used is from 0 to 50 L, preferably from 0.1 to 3.0 L, with respect to 1 mole of the compound represented by Formula [XXX].
    [0286] As the solvent and the base for use in the present process, the same ones mentioned in Process 1 of Production Method 1 can be exemplified.
    [0287] Examples of the acid for use in the present process may include mineral acids such as hydrochloric acid, hydrobromic acid and sulfuric acid; organic acids such as formic acid, acetic acid, methane sulfonic acid and p-toluenesulfonic acid; and the like.
    [0288] After completion of the reaction, the compound represented by Formula [I] that is a desired product of the present reaction can be collected from the reaction system by a usual method and, as the case requires, purified by a manipulation such as column chromatography or recrystallization. <Production Method 10>(Process 22)
    [0289]
    [0290] (wherein R, R1, R2, Y and m have the same meanings as defined above and R14 is a C1-6 alkyl group, a C1-6 acyl group or an optionally substituted benzyl group).
    [0291] The compound represented by Formula [XXXIII] can be produced by applying the compound represented by Formula [XXXII] to a hydrolysis with acid or base, or to a hydrogenolysis by a catalytic reduction method which employs the use of hydrogen gas and a suitable catalyst, in a suitable solvent or in the absence of a solvent. The compound represented by Formula [XXXII] can be produced by allowing the compound represented by Formula [XV] to react with an alcohol compound R14-OH or a carboxylic compound R14-C(=O)OH, according to the method described in Process 9 of Production Method 3.
    [0292] The reaction temperature of the present reaction is in the arbitrarily range of from 0°C to reflux temperature in the reaction system, preferably from 0 to 150°C.
    [0293] The reaction time of the present reaction varies according to a reaction temperature, a reactant, a reaction amount, or the like, but is between 1 and 120 hours.
    [0294] For the amount of agents to be provided in the present reaction, 1 to 10, preferably 1 to 3 equivalents of acid or base; and 0.001 to 1, preferably 0.01 to 0.5 equivalents of the catalyst are used, with respect to 1 equivalent weight of the compound represented by Formula [XXXII]. In addition, the amount of solvent to be used is from 0 to 50 L, preferably from 0.1 to 3.0 L, with respect to 1 mole of the compound represented by Formula [XXXII].
    [0295] As the solvent, the acid and the base for use in the present process, the same ones mentioned in Process 5 of Production Method 1 can be exemplified. As the catalyst, the same one mentioned in Process 8 of Production Method 2 can be exemplified.
    [0296] After completion of the reaction, the compound represented by Formula [XXXIII] that is a desired product of the present reaction can be collected from the reaction system by a usual method and, as the case requires, purified by a manipulation such as column chromatography or recrystallization. (Process 23)
    [0297]
    [0298] (wherein R, R1, R2, Y and m have the same meanings as defined above; and R15 is a C1-10 alkyl group, a C1-6 haloalkyl group, a G3-8 cycloalkyl group, a C3-8 cycloalkyl C1-3 alkyl group, an optionally substituted benzyl group, a C2-6 alkenyl group or a C2-6 alkynyl group, provided that when R15 is a C1-6 haloalkyl group, L1 is a leaving group having a higher reactivity than that of a halogen atom remained after haloalkylation. For example, when R15 is a CHF2 group, L1 is a chlorine atom or a bromine atom and when R15 is a CH2CF3 group, L1 is a chlorine atom, a bromine atom, an iodine atom, a p-toluenesulfonyloxy group, a methylsulfonyloxy group, a trifluoromethylsulfonyloxy group, or the like).
    [0299] The compound represented by Formula [XXXV] can be produced by allowing the compound represented by Formula [XXXIII] to react with the compound represented by Formula [XXXIV] in a suitable solvent or in the absence of a solvent, in the presence or absence of a base.
    [0300] The reaction temperature of the present reaction is in the arbitrarily range of from 0°C to reflux temperature in the reaction system, preferably from 0 to 150°C.
    [0301] The reaction time of the present reaction varies according to a reaction temperature, a reactant, a reaction amount, or the like, but is between 1 and 120 hours.
    [0302] For the amount of agents to be provided in the present reaction, 1 to 5, preferably 1 to 2 equivalents of the compound represented by Formula [XXXIV]; and 0 to 3, preferably 1 to 1.5 equivalents of the base are used, with respect to 1 equivalent of the compound represented by Formula [XXXIII]. In addition, the amount of solvent to be used is from 0 to 50 L, preferably from 0.1 to 3.0 L, with respect to 1 mole of the compound represented by Formula [XXXIII].
    [0303] As the solvent and the base for use in the present process, the same ones mentioned in Process 4 of Production Method 1 can be exemplified.
    [0304] After completion of the reaction, the compound represented by Formula [XXXV] that is a desired product of the present reaction can be collected from the reaction system by a usual method and, as the case requires, purified by a manipulation such as column chromatography or recrystallization. <Intermediate Production Method 1>(Process 24)
    [0305]
    [0306] (wherein R and R3 have the same meanings as defined above and X4 is a hydrogen atom, a C1-10 alkyl group, a C3-8 cycloalkyl group or a C1-6 haloalkyl group).
    [0307] The compound represented by Formula [XXXVII] can be produced by allowing the compound represented by Formula [XXXVI] with thiourea in a suitable solvent, in the presence of a suitable base.
    [0308] The reaction temperature of the present reaction is in the arbitrarily range of from 0°C to reflux temperature in the reaction system, preferably from 10 to 150°C.
    [0309] The reaction time of the present reaction varies according to a reaction temperature, a reactant, a reaction amount, or the like, but is between 0.5 and 120 hours.
    [0310] For the amount of agents to be provided in the present reaction, 1 to 2 equivalents of the thiourea and 1 to 5 equivalents of the base are used, with respect to 1 equivalent of the compound represented by Formula [XXXVI]. In addition, the amount of solvent to be used is from 0.1 to 50 L, preferably from 0.1 to 3.0 L, with respect to 1 mole of the compound represented by Formula [XXXVI].
    [0311] As the solvent and the base for use in the present process, the same ones mentioned in Process 1 of Production Method 1 can be exemplified.
    [0312] After completion of the reaction, the compound represented by Formula [XXXVII] that is a desired product of the present reaction can be used in the subsequent process without being isolated and purified, but can be also collected from the reaction system by a usual method and, as the case requires, purified by a manipulation such as column chromatography or recrystallization. (Process 25)
    [0313]
    [0314] (wherein R, R4, L and X4 have the same meanings as defined above).
    [0315] The compound represented by Formula [XXXVIII] can be produced by allowing the compound represented by Formula [XXXVII] to react with the compound represented by Formula [IV] in a suitable solvent, in the presence of a suitable base.
    [0316] The reaction temperature of the present reaction is in the arbitrarily range of from 0°C to reflux temperature in the reaction system, preferably from 10 to 150°C.
    [0317] The reaction time of the present reaction varies according to a reaction temperature, a reactant, a reaction amount, or the like, but is between 1 and 72 hours.
    [0318] For the amount of agents to be provided in the present reaction, 1 to 3 equivalents of the compound represented by Formula [IV] and 1 to 3 equivalents of the base are used, with respect to 1 equivalent of the compound represented by Formula [XXXVII]. In addition, the amount of solvent to be used is from 0.1 to 50 L, preferably from 0.1 to 3.0 L, with respect to 1 mole of the compound represented by Formula [XXXVII].
    [0319] As the solvent and the base for use in the present process, the same ones mentioned in Process 1 of Production Method 1 can be exemplified.
    [0320] After completion of the reaction, the compound represented by Formula [XXXVIII] that is a desired product of the present reaction can be collected from the reaction system by a usual method and, as the case requires, purified by a manipulation such as column chromatography or recrystallization. (Process 26)
    [0321]
    [0322] (wherein R, R4, X1 and X4 have the same meanings as defined above).
    [0323] The compound represented by Formula [XXXIX] can be produced by allowing the compound represented by Formula [XXXVIII] to react with a halogenating agent in a suitable solvent or in the absence of a solvent. Also, a suitable catalyst can be added for the production.
    [0324] The reaction temperature of the present reaction is in the arbitrarily range of from 0°C to reflux temperature in the reaction system, preferably from 0 to 150°C.
    [0325] The reaction time of the present reaction varies according to a reaction temperature, a reactant, a reaction amount, or the like, but is between 1 and 72 hours.
    [0326] For the amount of agents to be provided in the present reaction, 1 to 5 equivalents of the halogenating agent and 0 to 1.0 equivalent of the catalyst are used, with respect to 1 equivalent of the compound represented by Formula [XXXVIII]. In addition, the amount of solvent to be used is from 0 to 50 L, preferably from 0 to 3.0 L, with respect to 1 mole of the compound represented by Formula [XXXVIII].
    [0327] As the solvent, the halogenating agent and the catalyst for use in the present process, the same ones mentioned in Process 3 of Production Method 1 can be exemplified.
    [0328] After completion of the reaction, the compound represented by Formula [XXXIX] that is a desired product of the present reaction can be collected from the reaction system by a usual method and, as the case requires, purified by a manipulation such as column chromatography or recrystallization. <Production Method 11>(Process 27)
    [0329]
    [0330] (wherein R, R1, R2, X and Y have the same meanings as defined above; and p is 0, 1, or 2, while when p is 1 or greater, Yp+1 may be the same with or different from each other).
    [0331] The compound represented by Formula [I] can be produced by allowing the compound represented by Formula [XL] to react with an electrophilic agent in a suitable solvent or in the absence of a solvent.
    [0332] The reaction temperature of the present reaction is in the arbitrarily range of from 0°C to reflux temperature in the reaction system, preferably from 0 to 150°C.
    [0333] The reaction time of the present reaction varies according to a reaction temperature, a reactant, a reaction amount, or the like, but is between 1 and 120 hours.
    [0334] For the amount of agent to be provided in the present reaction, 1 to 10, preferably 1 to 3 equivalents of the electrophilic agent is used, with respect to 1 equivalent of the compound represented by Formula [XL]. In addition, the amount of solvent to be used is from 0 to 50 L, preferably from 0.1 to 3.0 L, with respect to 1 mole of the compound represented by Formula [XL].
    [0335] As the solvent for use in the present process, the same one mentioned in Process 4 of Production Method 1 can be exemplified.
    [0336] Examples of the electrophilic agent that can be used in the present process may include a halogenating agent such as chlorine, bromine, N-bromosuccinimide, N-chlorosuccinimide, MEC-03 or MEC-31 (trade name by Daikin Ltd.), Selectfluor (trade name by Air Products Inc.), F-PLUS-B800, B500, or B300 (trade names by Tosoh F-TECH, Inc.) or sulfuryl chloride; a nitrating agent such as nitric acid, fuming nitric acid or acetyl nitrate; a chlorosulfonylation agent such as chlorosulfuric acid; a thiocyanating agent employing sodium thiocyanate or potassium thicyanate and chlorine, bromine, N-bromosuccinimide, N-chlorosuccinimide or sulfuryl chloride; and the like.
    [0337] After completion of the reaction, the compound represented by Formula [I] that is a desired product of the present reaction can be collected from the reaction system by a usual method and, as the case requires, purified by a manipulation such as column chromatography or recrystallization. <Intermediate Production Method 2>(Process 28)
    [0338]
    [0339] (wherein R, R4 and X1 have the same meanings as defined above; R16 is a C1-10 alkyl group, a C3-8 cycloalkyl group, a C3-8 cycloalkyl C1-3 alkyl group, a C2-6 alkynyl group or a C2-6 alkenyl group; and X4 is a halogen atom).
    [0340] The compound represented by Formula [XLIII] can be produced by allowing the compound represented by Formula [VIa] to react with the compound represented by Formula [XLI] or Formula [XLII] in a suitable solvent or in the absence of a solvent, in the presence or absence of a base and a catalyst.
    [0341] The reaction temperature of the present reaction is in the arbitrarily range of from 0°C to reflux temperature in the reaction system, preferably from 0 to 150°C.
    [0342] The reaction time of the present reaction varies according to a reaction temperature, a reactant, a reaction amount, or the like, but is between 1 and 120 hours.
    [0343] For the amount of agents to be provided in the present reaction, 1 to 3 equivalents of the compound represented by Formula [XLI] or Formula [XLII]; 0 to 3 equivalents of the base; and 0 to 0.5 equivalent of the catalyst are used, with respect to 1 equivalent of the compound represented by Formula [VIa]. In addition, the amount of solvent to be used is from 0 to 50 L, preferably from 0.1 to 3.0 L, with respect to 1 mole of the compound represented by Formula [VIa].
    [0344] The solvent to be provided for the present reaction may be any solvent as long as it is an inert solvent not inhibiting the process of the present reaction. Examples thereof may include aliphatic hydrocarbons such as pentane, hexane, cyclohexane and petroleum ether; aromatic hydrocarbons such as toluene and xylene; ethers such as diethylether, diisopropylether, tert-butylmethylether, dioxane, 1,2-dimethoxyethane and tetrahydrofuran; alcohols such as methanol, ethanol, 1-propanol, 2-propanol, 1-butanol and tert-butanol; water; and a mixture thereof.
    [0345] Examples of the base to be provided for the present reaction may include organic bases such as pyridine, triethylamine, tributylamine and 1,8-diazabicyclo[5.4.0]-7-undecene; and inorganic bases such as alkali metal hydroxide, for example, sodium hydroxide or potassium hydroxide, alkaline-earth metal hydroxide, for example, calcium hydroxide or magnesium hydroxide, alkali metal carbonates, for example, sodium carbonate or potassium carbonate and alkali metal bicarbonates, for example, sodium bicarbonate or potassium bicarbonate.
    [0346] As the catalyst to be provided in the present reaction, a palladium catalyst such as palladium acetate, tetrakis(triphenylphosphine)palladium, or (diphenyl-phosphinoferrocene)palladium dichloride can be exemplified.
    [0347] After completion of the reaction, the compound represented by Formula [XLIII] that is a desired product of the present reaction can be collected from the reaction system by a usual method and, as the case requires, purified by a manipulation such as column chromatography or recrystallization. <Intermediate Production Method 3>(Process 29)
    [0348]
    [0349] (wherein R, R4 and X1 have the same meanings as defined above).
    [0350] The compound represented by Formula [XLIV] can be produced by iodizing the compound represented by Formula [VIa] using hydriodic acid.
    [0351] The reaction temperature of the present reaction is in the arbitrarily range of from 0°C to reflux temperature in the reaction system, preferably from 0 to 150°C.
    [0352] The reaction time of the present reaction varies according to a reaction temperature, a reactant, a reaction amount, or the like, but is between 1 and 120 hours.
    [0353] For the amount of agent to be provided in the present reaction, 1 to 20, preferably 1 to 5 equivalents of the hydriodic acid is used, with respect to 1 equivalent of the compound represented by Formula [VIa].
    [0354] After completion of the reaction, the compound represented by Formula [XLIV] that is a desired product of the present reaction can be collected from the reaction system by a usual method and, as the case requires, purified by a manipulation such as column chromatography or recrystallization. (Process 30)
    [0355]
    [0356] (wherein R, R4 and X1 have the same meanings as defined above and R17 is a C1-6 haloalkyl group).
    [0357] The compound represented by Formula [XLV] can be produced by haloalkylating the compound represented by Formula [XLIV] using a haloalkylating agent in a suitable solvent or in the absence of a solvent, in the presence or absence of a base and a catalyst, according to a method described in Synthesis, Vol. 5, 798-803 (2005).
    [0358] The reaction temperature of the present reaction is in the arbitrarily range of from 0°C to reflux temperature in the reaction system, preferably from 0 to 180°C.
    [0359] The reaction time of the present reaction varies according to a reaction temperature, a reactant, a reaction amount, or the like, but is between 1 and 120 hours.
    [0360] For the amount of agents to be provided in the present reaction, 1 to 3 equivalents of the haloalkylating agent; 0 to 3 equivalents of the base; and 0 to 0.5 equivalent of the catalyst are used, with respect to 1 equivalent of the compound represented by Formula [XLIV]. In addition, the amount of solvent to be used is from 0 to 50 L, preferably from 0.1 to 3.0 L, with respect to 1 mole of the compound represented by Formula [XLIV].
    [0361] Examples of the haloalkylating agent to be provided in the present reaction may include sodium chlorodifluoroacetate, sodium trifluoroacetate, trifluoromethyl iodide, 1,1,2,2,2-pentafluoroethyl iodide, 1,1,2,2,3,3,4,4,4-nonafluorobutyl iodide, trifluoromethyltrimethylsilane, trifluoromethyl-triethylsilane and the like.
    [0362] Examples of the base to be provided in the present reaction may include potassium fluoride, sodium fluoride, cesium fluoride and the like.
    [0363] Examples of the catalyst to be provided in the present reaction may include copper powder, copper iodide and the like.
    [0364] The solvent to be provided in the present reaction may be any solvent as long as it is an inert solvent not inhibiting the process of the present reaction. Examples thereof may include amides such as N,N-dimethylformamide, N,N-dimethylacetoamide, N-methylpyrrolidinone and 1,3-dimethyl-2-imidazolidinone; dimethylsulfoxide; pyridine; and the like.
    [0365] After completion of the reaction, the compound represented by Formula [XLV] that is a desired product of the present reaction can be collected from the reaction system by a usual method and, as the case requires, purified by a manipulation such as column chromatography or recrystallization. <Intermediate Production Method 4>(Process 31)
    [0366]
    [0367] (wherein R, R1, R2, R4, X1 and X3 have the same meanings as defined above).
    [0368] The compound represented by Formula [XLVII] can be produced by allowing the compound represented by Formula [XLVI] to react with the compound represented by Formula [XVI] in a suitable solvent, in the presence of a suitable base. Also, a suitable catalyst can be added for the production.
    [0369] The reaction temperature of the present reaction is in the arbitrarily range of from -30°C to reflux temperature in the reaction system, preferably from 0 to 150°C.
    [0370] The reaction time of the present reaction varies according to a reaction temperature, a reactant, a reaction amount, or the like, but is between 1 and 120 hours.
    [0371] For the amount of agents to be provided in the present reaction, 1 to 3 equivalents of the compound represented by Formula [XVI]; 1 to 3 equivalents of the base; and 0 to 0.5 equivalent of the catalyst are used, with respect to 1 equivalent of the compound represented by Formula [XLVI]. In addition, the amount of solvent to be used is from 0.1 to 50 L, preferably from 0.1 to 3.0 L, with respect to 1 mole of the compound represented by Formula [XLVI].
    [0372] As the solvent, the base and the catalyst, for use in the present process, the same ones mentioned in Process 9 of Production Method 3 can be exemplified.
    [0373] After completion of the reaction, the compound represented by Formula [XLVII] that is a desired product of the present reaction can be collected from the reaction system by a usual method and, as the case requires, purified by a manipulation such as column chromatography or recrystallization. <Production Method 12>(Process 32)
    [0374]
    [0375] (wherein R, R1, R2, R16, Y, m and X4 have the same meanings as defined above and X5 is a halogen atom, a C1-6 alkylsulfonyloxy group or a C1-6 haloalkylsulfonyloxy group).
    [0376] The compound represented by Formula [XLIX] can be produced by allowing the compound represented by Formula [XLVIII] to react with the compound represented by Formula [XLI] or [XLII] in a suitable solvent or in the absence of a solvent, in the presence or absence of a base and a catalyst.
    [0377] The reaction temperature of the present reaction is in the arbitrarily range of from 0°C to reflux temperature in the reaction system, preferably from 0 to 150°C.
    [0378] The reaction time of the present reaction varies according to a reaction temperature, a reactant, a reaction amount, or the like, but is between 1 and 120 hours.
    [0379] For the amount of agents to be provided in the present reaction, 1 to 3 equivalents of the compound represented by Formula [XLI] or [XLII]; 0 to 3 equivalents of the base; and 0 to 0.5 equivalent weight of the catalyst are used, with respect to 1 equivalent of the compound represented by Formula [XLVIII]. In addition, the amount of solvent to be used is from 0 to 50 L, preferably from 0.1 to 3.0 L, with respect to 1 mole of the compound represented by Formula [XLVIII].
    [0380] As the solvent, the base and the catalyst to be provided in the present reaction, the same ones mentioned in Process 28 of Production Method 13 can be exemplified.
    [0381] After completion of the reaction, the compound represented by Formula [XLIX] that is a desired product of the present reaction can be collected from the reaction system by a usual method and, as the case requires, purified by a manipulation such as column chromatography or recrystallization.
    [0382] The plant disease control agent for agricultural or horticultural use according to the present invention is formed by containing the aminopyrimidine derivative represented by Formula [I] or an agriculturally acceptable salt thereof as the active ingredient.
    [0383] In the case of using the compound of present application as a plant disease control agent for agricultural or horticultural use, it may be used singly or alternatively as the active ingredient in a suitable form according to its purpose.
    [0384] In general, an active ingredient is diluted with an inert liquid or solid carrier and a surfactant and any others are added thereto as necessary, so as to be formed into a formulation of powder, wettable powder, emulsion, granules, or the like for a use. A ratio of the active ingredient to be blended may be suitably selected depending on the situation, but it is appropriate to be in the range of from 0.1 to 50% (by weight) in the case of powder and granule, or from 5 to 80% (by weight) in the case of emulsion and wettable powder.
    [0385] Examples of the carrier to be used upon formulation may include solid carriers such as talc, bentonite, zeolite, clay, kaolin, diatomite, acid clay, white clay, white carbon, vermiculite, pearlite, pumice, calcium carbonate, slaked lime, silica sand, ammonium sulfate, urea and wooden powder; liquid carriers such as n-paraffin, isoparaffin, naphthene, isopropyl alcohol, cyclohexanol, ethylene glycol, diethylene glycol, propylene glycol, polyethylene glycol, polypropylene glycol, xylene, alkyl benzene, cyclohexane, alkylnaphthalene, fatty acid methyl ester, N-alkylpyrrolidone, isophorone, coconut oil, soybean oil and water; and the like.
    [0386] Examples of the surfactant and dispersion may include sorbitan fatty acid ester, metal alkylbenzenesulfonate, metal dinaphthylmethane disulfonate, alcohol sulfate ester, alkyl aryl sulfonate, lignin sulfonate, metal dialkylsulfosuccinate, polyoxyethyleneglycolether, polyoxyethylene alkylaryl ether, a polyoxyethylenealkylaryl polymer, polyoxyethylene alkylaryl ether sulfonate, polyoxyethylene sorbitan monoalkylate, a salt of β-naphthalenesulfonate-formalin condensate, polyoxyethylene styrenated phenylethersulfate and the like.
    [0387] Examples of the auxiliary agent may include carboxymethyl cellulose, alphanized starch, modified dextrin, polyethylene glycol, xanthan gum, gum arabic, silicone and the like.
    [0388] Furthermore, the plant disease control agent for agricultural or horticultural use according to the invention can be mixed with or used in combination with other known active compounds such as insecticide, miticide, insect growth regulator, nematocide, fungicide, plant disease control agent, herbicide, plant growth regulator, fertilizer and soil conditioner, if needed, in addition to the compound of present application which is an active ingredient for various formulations described above.
    [0389] Known fungicidal compounds which may be mixed or used in combination will be exemplified by: benomyl, carbendazim, fuberidazole, thiabendazole, thiophanate, thiophanate-methyl, chlozolinate, iprodione, procymidone, vinclozolin, azaconazole, bitertanol, bromuconazole, cyproconazole, difenoconazole, diniconazole, epoxiconazole, fenarimol, fenbuconazole, fluquinconazole, flusilazole, flutriafol, hexaconazole, imazalil, imibenconazole, ipconazole, metconazole, myclobutanil, nuarimol, oxpoconazole fumarate, paclobutrazol, pefurazoate, penconazole, prochloraz, propiconazole, prothioconazole, pyrifenox, simeconazole, tebuconazole, tetraconazole, triadimefon, triadimenol, triflumizole, triforine, triticonazole, benalaxyl, furalaxyl, mefenoxam, metalaxyl, metalaxyl-M, ofurace, oxadixyl, aldimorph, dodemorph, fenpropidin, fenpropimorph, piperalin, spiroxamine, tridemorph, edifenphos, iprobenfos, isoprothiolane, pyrazophos, benodanil, boscalid, carboxin, fenfuram, flutolanil, furametpyr, mepronil, oxycarboxin, penthiopyrad, thifluzamide, bupirimate, dimethirimol, ethirimol, cyprodinil, mepanipyrim, pyrimethanil, diethofencarb, azoxystrobin, dimoxystrobin, enestrobin, famoxadone, fenamidone, fluoxastrobin, kresoxim-methyl, metominostrobin, orysastrobin, picoxystrobin, pyraclostrobin, trifloxystrobin, fenpiclonil, fludioxonil, quinoxyfen, biphenyl, chloroneb, dicloran, etridiazole, quintozene, tecnazene, tolclofos-methyl, fthalide, pyroquilon, tricyclazole, carpropamid, diclocymet, fenoxanil, fenhexamid, pyributicarb, polyoxin, pencycuron, cyazofamid, zoxamide, blasticidin-S, kasugamycin, streptomycin, validamycin, cymoxanil, iodocarb, propamocarb, prothiocarb, binapacryl, dinocap, ferimzone, fluazinam, TPTA(fentin acetate), TPTC(fentin chloride), TPTH(fentin hydroxide, oxolinic acid, hymexazol, octhilinone, fosetyl, phosphonic acid and a salt thereof, tecloftalam, triazoxide, flusulfamide, diclomezine, silthiofam, diflumetorim, benthiavalicarb-isopropyl, dimethomorph, flumorph, iprovalicarb, mandipropamid, oxytetracycline, methasulfocarb, chinomethionat, fluoroimide, milneb, copper hydroxide, copper octanoate, copper oxychloride, copper sulfate, cuprous oxide, mancopper, oxine-copper, sulfur, ferbam, mancozeb, maneb, metiram, propineb, thiram, zineb, ziram, captafol, captan, folpet, chlorothalonil, dichlofluanid, tolylfluanid, anilazine, dodine, guazatine, iminoctadine, dithianon, acibenzolar-S-methyl, probenazole, tiadinil, ethaboxam, cyflufenamid, proquinazid, metrafenone, fluopicolide, dazomet, difenzoquat, amisubrom, Bordeaux mixture, F-991, nabam, phenazine oxide, polycarbamate, or pyribencarb.
    [0390] Known fungicidal and nematicidal compounds which may be mixed or used in combination will be exemplified by: demeton-S-methyl, bioallethrin, bioallethrin S-cyclopentenylisomer, famphur, DDT, DNOC, EPN, XMC, acrinathrin, azadirachtin, azamethiphos, azinphos-ethyl, azinphos-methyl, acequinocyl, acetamiprid, acetoprol, acephate, azocyclotin, abamectin, amitraz, alanycarb, aldicarb, alphacypermethrin, allethrin[(1R)-isomers], d-cis-trans Allethrin, d-trans Allethrin, isocarbophos, isoxathion, isofenphos, isoprocarb, imicyafos, imidacloprid, imiprothrin, indoxacarb, esfenvalerate, ethiofencarb, ethiprole, ethion, ethiprole, etoxazole, etofenprox, ethoprophos, emamectin, endosulfan, Empenthrin, empenthrin[(EZ)-(1R)-isomers], oxamyl, oxydemeton-methyl, omethoate, cadusafos, cartap, carbaryl, carbosulfan, carbofuran, gamma-cyhalothrin, gamma-BCH(Lindane), xylylcarb, quinalphos, kinoprene, quinomethionate, chinomethionat, coumaphos, clothianidin, clofentezine, chromafenozide, chlorethoxyfos, chlordane, chlorpyrifos, chlorpyrifos-methyl, chlorfenapyr, chlorfenvinphos, chlorfluazuron, chlormephos, cyenopyrafen, cyanophos, diafenthiuron, diethofencarb, dienochlor, dicrotophos, dichlofenthion, cycloprothrin, dichlorvos, dicofol, disulfoton, dinotefuran, cyhalothrin, cyphenothrin[(1R)-trans-isomers], cyfluthrin, diflubenzuron, cyflumetofen, cyhexatin, cypermethrin, dimethylvinphos, dimethoate, tartaremetic, silafluofen, cyromazine, spinosad, spirodiclofen, spirotetramat, spiromesifen, sulfotep, zeta-cypermethrin, diazinon, tau-fluvalinate, thiacloprid, thiamethoxam, thiodicarb, thiocyclam, thiosultap-sodium, thiofanox, thiometon, tetrachlorvinphos, tetradifon, tetramethrin, tetramethrin[(1R)-isomers], depallethrin, tebupirimfos, tebufenozide, tebufenpyrad, tefluthrin, teflubenzuron, temephos, deltamethrin, terbufos, tralomethrin, transfluthrin, triazamate, triazophos, trichlorfon, tribufos, triflumuron, trimethacarb, tolfenpyrad, naled, nicotine, nitenpyram, nemadectin, novaluron, noviflumuron, hydroprene, vamidothion, parathion, parathion-methyl, halfenprox, halofenozide, bioresmethrin, bistrifluron, pyridaphenthion, hydramethylnon, bifenazate, bifenthrin, piperonyl butoxide, pymetrozine, pyraclofos, pyridafenthion, pyridaben, pyridalyl, pyriproxyfen, pirimicarb, pyrimidifen, pirimiphos-methyl, Pyrethrins(pyrethrum), fipronil, fenazaquin, fenamiphos, fenisobromolate, fenitrothion, fenoxycarb, phenothrin[(1R)-transisomer], fenobucarb, fenthion, phenthoate, fentrifanil, fenvalerate, fenpyroximate, fenbutatin oxide, fenpropathrin, butocarboxim, butoxycarboxim, buprofrzin, furathiocarb, prallethrin, fluacrypyrim, flucycloxuron, flucythrinate, flusulfamide, fluvalinate, flupyrazofos, flufenerim, flurenoxuron, Flubendiamide, flumethrin, flurimfen, prothiofos, flonicamid, propaphos, propargite, profenofos, propetamphos, propoxur, bromopropylate, beta-cyfluthrin, beta-cypermethrin, hexythiazox, hexaflumuron, heptenophos, permethrin, bensultap, benzoximate, bendiocarb, benfuracarb, borax, phoxim, phosalone, fosthiazate, phosphamidon, phosmet, formetanate, phorate, malathion, milbemectin, mecarbam, mesulfenfos, methomyl, metaflumizon, methamidophos, metham-ammonium, metham-sodium, methiocarb, methidathion, methoxychlor, methoxyfenozide, methothrin, methoprene, metolcarb, mevinphos, monocrotophos, lambda-cyhalothrin, rynaxypyr, aluminium phosphide, phosphine, lufenuron, resmethrin, lepmectin, rotenone, Bacillus sphaericus, Bacillus thuringiensis subsp. Aizawai, Bacillus thuringiensis subsp. Israelensis, Bacillus thuringiensis subsp. Kurstaki, Bacillus thuringiensis subsp. tenebrionis, CL900167, NNI-0101, RU15525, XDE-175, or ZXI8901.
    [0391] Known herbicidal compounds which may be mixed or used in combination will be exemplified by: 2,3,6-TBA, 2,4-D, 2,4-DB, DNOC, EPTC, HC-252, MCPA, MCPA-thioethyl, MCPB, S-metolachlor, TCA, ioxynil, aclonifen, azafenidin, acifluorfen, azimsulfuron, asulam, acetochlor, atrazine, anilofos, amicarbazone, amidosulfuron, amitrole, aminopyralid (DE-750), amiprophos-methyl, ametryn, alachlor, alloxydim, ancymidol, iodosulfulon-methyl-sodium, isouron, isoxachlortole, isoxaflutole, isoxaben, isoproturon, imazaquin, imazapyr, imazamethabenz-methyl, imazapic, imazamox, imazethapyr, imazosulfuron, indanofan, esprocarb, ethametsulfuron-methyl, ethalfluralin, ethidimuron, ethoxysulfuron, ethofumesate, etobenzanid, oxadiazon, oxadiargyi, oxaziclomefone, oxasulfuron, oxyfluorfen, oryzalin, orbencarb, cafenstrole, carfentrazone-ethyl, karbutilate, carbetamide, quizalofop-P, quizalofop-P-ethyl, quizalofop-P-tefuryl, quizalofop-ethyl, quinclorac, quinmerac, cumyluron, glyphosate, glyphosate-trimesium(sulfosate), glufosinate-ammonium, glufosinate-sodium, clethodim, clodinafop-propargyl, clopyralid, clomazone, chlomethoxyfen, clomeprop, cloransulam-methyi, chloramben, chloridazon, chlorimuron-ethyl, chlorsulfuron, chlorthal-dimethyl, chlorthiamid, chlorpropham, chlormequat chloride, chloroxuron, chlorotoluron, chlorobromuron, cyanazine, diuron, dicamba, cycloate, cycloxydim, diclosulam, cyclosulfamuron, dichlobenil, diclofop-methyl, dichlorprop, dichlorprop-P, diquat dibromide, dithiopyr, siduron, dinitramine, cinidon-ethyl, cinosulfuron, dinoseb, dinoterb, cyhalofop-butyl, diphenamid, difenzoquat, diflufenican, diflufenzopyr, diflumetorim, simazine, dimethachlor, dimethametryn, dimethenamid, simetryn, dimepiperate, dimefuron, cinmethylin, sulcotrione, sulfentrazone, sulfosulfuron, sulfometuronmethyl, sethoxydim, terbacil, daimuron, dalapon, thiazopyr, tiocarbazil, thiobencarb, thidiazimin, thidiazuron, thifensulfuron-methyl, desmedipham, desmetryne, thenylchlor, tebutam, tebuthiuron, tepraloxydim, tefuryltrion, terbuthylazine, terbutryn, terbumeton, tembotrione, topramezone, tralkoxydim, triaziflam, triasulfuron, triallate, trietazine, triclopyr, triflusulfuron-methyl, tritosulfuron, trifluralin, trifloxy-sulruron-sodium, tribenuron-methyl, naptalam, naproanilide, napropamide, nicosulfuron, neburon, norflurazon, vernolate, paraquat dichloride, haloxyfop, haloxyfop-P, haloxyfop-P-methyl, halosulfuron-methyl, pinoxaden, picloram, picolinafen, bispyribac-sodium, bifenox, piperophos, pyraclonil, pyrasulfotole, pyrazoxyfen, pyrazosulfuron-ethyl, pyrazolynate, bilanafos, pyraflufen-ethyl, pyridafol, pyrithiobac-sodium, pyridate, pyriftalid, pyributicarb, pyribenzoxim, pyrimisulfan, primisulfuron-methyl, pyriminobac-methyl, pyroxysulam, fenuron, fenoxaprop-P-ethyl, fenoxaprop-ethyl, fenclorim, fentrazamide, phenmedipham, foramsulfuron, butachlor, butafenacil, butamifos, butylate, butralin, butroxydim, flazasulfuron, flamprop-M, fluazifop-butyl, fluazifop-P-butyl, fluazolate, fluometuron, fluometuron, fluoroglycofen-ethyl, flucarbazone-sodium, flucetosulfuron, fluthiacet-methyl, flupyrsulfuron-methyl-sodium, flufenacet, flufenpyr-ethyl, flupropanate, flupoxame, flumioxazin, flumiclorac-pentyl, flumetsulam, fluridone, flurtamone, flurprimidol, fluroxypyr, flurochloridone, pretilachlor, prodiamine, prosulfuron, prosulfocarb, propaquizafop, propachlor, propazine, propanil, propyzamide, propisochlor, propham, profluazol, propoxyoarbazone, propoxycarbazone-sodium, profoxydim, bromacil, prometryn, prometon, bromoxynil, bromofenoxim, bromobutide, florasulam, hexazinone, pethoxamid, benazolin, penoxsulam, beflubutamid, pebulate, TM435, pendimethalin, benzfendizone, bensulide, bensulfuron-methyl, benzobicyclon, benzofenap, bentazone, pentanochlor, pentoxazone, benfluralin, benfuresate, fosamine, fomesafen, forchlorfenuron, maleic hydrazide, mecoprop, mecoprop-P, mesosulfuron-methyl, mesotrione, metazachlor, methabenzthiazuron, metamitron, metamifop, methyl-dimuron, metoxuron, metosulam, metsulfuron-methyl, metobromuron, metobenzuron, metolachlor, metribuzin, mepiquat chloride, mefenacet, monolinuron, molinate, lactofen, linuron, rimsulfuron, lenacil, prohexadione-calcium, or trinexapac-ethyl.
    [0392] The plant disease control agent for agricultural or horticultural use of the invention can be used directly in the form of those formulations, or by diluting the formulations, for foliage application, seed treatment, soil application, submerged application, nursery box application, or the like. The application amount varies depending on a kind of the compound to be used, target disease, growth pattern, degree of damage, environmental conditions, form of use and the like.
    [0393] For example, in the case of a direct use of powder or granular formulation, the amount should be arbitrarily selected from 0.1g to 5kg, preferably from 1g to 1kg per 10 are in terms of an active ingredient.
    [0394] Further, in the case of using in a liquid form of emulsion or wettable powder, the amount should be arbitrarily selected from 0.1 ppm to 10,000 ppm, preferably from 10 to 3,000 ppm.
    [0395] In the case of using for a nursery box application, a long-term effect can be exhibited by providing a formulation in which an elution property of the compound is controlled.
    [0396] The plant disease control agent for agricultural or horticultural use of the invention can control plant diseases caused by filamentous fungi, bacteria and virus, according to the above-described application patterns.
    [0397] Next, specific plant diseases will be exemplified without being limited thereto:
    [0398] Pseudoperonospora cubensis, Phytophthora melonis, Fusarium oxysporum, Pythium debaryanum, Corynespora cassiicola, Botrytis cinerea, Colletotrichum lagenarium, Sphaerotheca cucurbitae, Pseudomonas syringae, Pseudomonas solanacearum, Erysiphe graminis, Septoria nodorum, Septoria tritici, Puccinia recondite, Puccinia striiformis, Puccinia graminis, Pseudccercosporella herpotrichoides, Pyrenophora teres, Rhynchosporium secalis, Erwinia carotovora, Phytophthora infestans, Sclerotinia sclerotiorum, Cladosporium fulvum, Corynebacterium michiganense, Pyricularia oryzae, Rhizoctonia solani, Cochliobolus miyabeanus, Xanthomonas oryzae, Fusarium spp., Pythium spp., Rhizopus spp., Trichoderma sp., Burkholderia glumae, Burkholderia plantarii, Acidovorax avenae, Erwinia ananas, Venturia inaequalis, Alternaria mali, Gymnosporangium yamadae, Physalospora piricola, Alternaria kikuchiana, Phomopsis fukushii, Monilinia fructicola, Glomerella cingulata, Plasmopara viticola, Diaporthe citri, Elsinoe fawcetti and the like.
    [0399] Hereinafter, production methods of the derivative of Formula [I] that can be employed in the plant disease control agent for agricultural or horticultural use according to the invention, formulation methods and applications will be described in detail with reference to Examples below. However, the present invention is not limited to these Examples in any way. In the description below, '%' means 'percent by weight'. Methods for producing Production Intermediates of the compound of the invention will also be described. Examples[Example 1]Production of 5-sec-butyl-4-chloro-6-(4-methylpiperidin-1-yl)-2-(1H-pyrazol-1-yl)pyrimidine (Inventive Compound No. 1192)
    [0400] 0.6g of sodium hydride (purity: 60%, 13.9 mmol) was added to 30 ml of an N,N-dimethylformamide solution containing 0.9g (12.7 mmol) of 1H-pyrazole at room temperature and the mixture was stirred for 1 hour. Further, 10 ml of an N,N-dimethylformamide solution containing 4.0g (11.6 mmol) of 5-sec-butyl-4-chloro-6-(4-methylpiperidin-1-yl)-2-methylsulfonylpyrimidine was added thereto at room temperature and the mixture was stirred for 1 hour. After confirming the completion of reaction, the reaction solution was poured into water and extracted with diethylether. The obtained organic layer was washed with water and then dried over anhydrous magnesium sulfate. The insolubles were separated by filtration and then the solvent was distilled off under reduced pressure. Thus obtained residue was purified by silica gel column chromatography to obtain 3.7g of 5-sec-butyl-4-chloro-6-(4-methylpiperidin-1-yl)-2-(1H-pyrazol-1-yl)pyrimidine as a transparent liquid (yield: 95%).
    [0401] Refractive Index (nD 20) : 1.57211H-NMR Data (CDCl3/TMS δ (ppm)): 0.83 (3H, t, J=7.4 Hz), 1.01 (3H, d, J=6.6 Hz), 1.24-1.46 (5H, m), 1.60-1.89 (5H, m), 2.83-3.06 (3H, m), 3.71-3.75 (2H, m), 6.42-6.44 (1H, m), 7.79 (1H, bs), 8.48 (1H, d, J=2.7 Hz) [Example 2]Production of 5-sec-butyl-4-(4-methylpiperidin-1-yl)-2-(1H-pyrazol-1-yl)pyrimidine (Inventive Compound No. 1190)
    [0402] 0.3g (4.2 mmol) of anhydrous sodium acetate and 10mg of palladium carbon were added to 100 ml of a methanol solution containing 0.7g (2.1 mmol) of 5-sec-butyl-4-chloro-6-(4-methylpiperidin-1-yl)-2-(1H-pyrazol-1-yl)pyrimidine. A hydrogen gas was supplied under normal pressure and the mixture was stirred for 42 hours at room temperature. After confirming the completion of reaction, a catalyst was filtered off through celite. After concentrating thus obtained filtrate, water was added and extraction was subjected with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, the insolubles were separated by filtration and then the solvent was distilled off under reduced pressure. Thus obtained residue was purified by silica gel column chromatography to obtain 0.5g of 5-sec-butyl-4-(4-methylpiperidin-1-yl)-2-(1H-pyrazol-1-yl)pyrimidine as a colorless transparent oily substance (yield: 86%).
    [0403] Refractive Index (nD 20): 1.55651H-NMR Data (CDCl3/TMS δ (ppm)): 0.85 (3H, t, J=7.4 Hz), 1.00 (3H, d, J=6.3 Hz), 1.29-1.44 (5H, m), 1.57-1.78 (5H, m), 2.68-2.75 (1H, m), 2.89-3.04 (1H, m), 3.79-3.86 (2H, m), 6.42-6.43 (1H, m), 7.77 (1H, s), 8.25 (1H, s), 8.51 (1H, d, J=2.8 Hz) [Example 3]Production of 5-sec-butyl-6-(4-methylpiperidin-1-yl)-4-methylthio-2-(1H-pyrazol-1-yl)pyrimidine (Inventive Compound No. 1204)
    [0404] 0.3g (4.9 mmol) of sodium thiomethoxide was added to 10 ml of a tetrahydrofuran solution containing 1.5g (4.5 mmol) of 5-sec-butyl-4-chloro-6-(4-methylpiperidin-1-yl)-2-(1H-pyrazol-1-yl)pyrimidine and the mixture was stirred for 3 hours at room temperature. After confirming the completion of reaction, the reaction solution was poured into water and extracted with ethyl acetate. The obtained organic layer was dried over anhydrous magnesium sulfate. The insolubles were separated by filtration and then the solvent was distilled off under reduced pressure, to obtain 1.6g of 5-sec-butyl-6-(4-methylpiperidin-1-yl)-4-methylthio-2-(1H-pyrazol-1-yl)pyrimidine as a white powder (yield: quantitative).
    [0405] Meiting Point (°C): 69 to 711H-NMR Data (CDCl3/TMS δ (ppm)): 0.81 (3H, t, J=7.3 Hz), 0.99 (3H, d, J=6.4 Hz), 1.28-1.59 (6H, m), 1.74-1.96 (4H, m), 2.65 (3H, s), 2.86-3.03 (3H, m), 3.51-3.58 (2H, m), 6.42-6.43 (1H, m), 7.80 (1H, s), 8.54 (1H, d, J=1.8 Hz) [Example 4]Production of 5-sec-butyl-6-(4-methylpiperidin-1-yl)-4-methylsulfonyl-2-(1H-pyrazol-1-yl)pyrimidine (Inventive Compound No. 1206)
    [0406] 2.5g of m-chloroperbenzoic acid (purity: 70%, 10.1 mmol) was added to 100 ml of a dichloromethane solution containing 1.4g (4.1 nmol) of 5-sec-butyl-6-(4-methylpiperidin-1-yl)-4-methylthio-2-(1H-pyrazol-1-yl)pyrimidine under ice cooling and the mixture was stirred for 30 minutes. The mixture was further stirred for 72 hours at room temperature. After confirming the completion of reaction, the reaction solution was poured into water and extracted with dichloromethane. The obtained organic layer was washed with an aqueous solution of sodium bisulfite, water, an aqueous sodium bicarbonate solution and brine in the said order and then dried over anhydrous magnesium sulfate. The insolubles were separated by filtration and then the solvent was distilled off under reduced pressure, to obtain 1.3g of 5-sec-butyl-6-(4-methylpiperidin-1-yl)-4-methylsulfonyl-2-(1H-pyrazol-1-yl)pyrimidine as a pale yellow viscous substance (yield: 86%).
    [0407] 1H-NMR Data (CDCl3/TMS δ (ppm)): 0.85 (3H, t, J=7.4 Hz), 1.01 (3H, d, J=6.3 He), 1.35-1.43 (2H, m), 1,53 (3H, d, J=7.1 Hz), 1.61-1.81 (3H, m), 1.88-1.98 (2H, m), 2.99-3.07 (2H, m), 3.24-3.32 (1H, m), 3.45 (3H, s), 3.85 (2H, m), 6.46-6.48 (1H, m), 7.82 (1H, s), 8.44 (1H, d, J=2.2 Hz) [Example 5]Production of 5-sec-butyl-6-(4-methylpiperidin-1-yl)-2-(1H-pyrazol-1-yl)pyrimidine-4-carbonitrile (Inventive Compound No. 1215)
    [0408] 0.3g (5.4 mmol) of sodium cyanide was added to 10 ml of a dimethylsulfoxide solution containing 1.0g (2.7 mmol) of 5-sec-butyl-6-(4-methylpiperidin-1-yl)-4-methylsulfonyl-2-(1H-pyrazol-1-yl)pyrimidine and the mixture was stirred for 1.5 hours at room temperature. After confirming the completion of reaction, the reaction solution was poured into water and extracted with diethylether. The obtained organic layer was dried over anhydrous magnesium sulfate. The insolubles were separated by filtration and then the solvent was distilled off under reduced pressure to obtain 0.6g of 5-sec-butyl-6-(4-methylpiperidin-1-yl)-2-(1H-pyrazol-1-yl)pyrimidine-4-carbonitrile as a yellow viscous substance (yield: 63%).
    [0409] Refractive Index (nD 20): 1.57001H-NMR Data (CDCl3/TMS δ (ppm)) : 0.87 (3H, t, J=7.3 Hz), 1.02 (3H, d, J=6.6 Hz), 1.24-1.44 (2H, m), 1.56 (3H, d, J=7.1 Hz), 1.64-2.05 (5H, m), 2.74-2.82 (1H, m), 2.97-3.11 (2H, m), 3.83-3.90 (2H, m), 6.46 (1H, bs), 7.81 (1H, s), 8.49 (1H, d, J=2.5 Hz) [Example 6]Production of 5-sec-butyl-4-methyl-6-(4-methylpiperidin-1-yl)-2-(1H-pyrazol-1-yl)pyrimidine (Inventive Compound No. 1225)
    [0410] 15 ml of a 12N hydrochloric acid solution containing 1.6g (3.6 mmol) of dimethyl 2-[5-sec-butyl-6-(4-methylpiperidin-1-yl)-2-(1H-pyrazol-1-yl)pyrimidin-4-yl]malonate was stirred for 32 hours at 80°C. After confirming the completion of reaction, the reaction solution was poured into water, neutralized with a 10% aqueous sodium hydroxide solution and extracted with ethyl acetate. The obtained organic layer was washed with water and then dried over anhydrous magnesium sulfate. The insolubles were separated by filtration and then the solvent was distilled off under reduced pressure. Thus obtained residue was purified by silica gel column chromatography to obtain 0.1g of 5-sec-butyl-4-methyl-6-(4-methylpiperidin-1-yl)-2-(1H-pyrazol-1-yl)pyrimidine as a pale yellow oily substance (yield: 12%).
    [0411] Refractive Index (nD 20): 1.55811H-NMR Data (CDCl3/TMS δ (ppm)): 0.84 (3H, t, J=7.4 Hz), 1.00 (3H, d, J=6.6 Hz), 1.33-1.45 (5H, m), 1.64-1.78 (5H, m), 2.58 (3H, s), 2.82-3.01 (3H, m), 3.55-3.60 (2H, m), 6.41 (1H, bs), 7.76 (1H, s), 8.52 (1H, d, J=2.7 Hz) [Example 7]Production of 5-sec-butyl-6-chloro-2-(1H-pyrazol-1-yl)-N-(2,2,2-trifluoroethyl)pyrimidine-4-amine (Inventive Compound No. 0350)
    [0412] 0.6g (9.5 mmol) of 1H-pyrazole and 2.2g (15.8 mmol) of potassium carbonate were added to 20 ml of an N,N-dimethylformamide solution containing 2.7g (7.9 mmol) of 5-sec-butyl-6-chloro-2-methylsulfonyl-N-(2,2,2-trifluoroethyl)pyrimidine-4-amine at room temperature and the mixture was stirred for 8 hours at 60°C. After confirming the completion of the reaction, the reaction solution was poured into water and extracted with diethylether. The obtained organic layer was washed with water and then dried over anhydrous magnesium sulfate. The insolubles were separated by filtration and then the solvent was distilled off under reduced pressure. Thus obtained residue was purified by silica gel column chromatography to obtain 1.6g of 5-sec-butyl-6-chloro-2-(1H-pyrazol-1-yl)-N-(2,2,2-trifluoroethyl)pyrimidine-4-amine as a white powder (yield: 61%).
    [0413] Melting Point (°C): 137 to 1391H-NMR Data (CDCl3/TMS δ (pom)): 0.92 (t, 3H), 1.35 (d, 3H), 1.75 (m, 2H), 3.42 (br, 1H), 4.38 (m, 2H), 5.23 (br, 1H), 6.45 (t, 1H), 7.80 (d, 1H), 8.46 (d, 1H) [Example 8]Production of 5-sec-butyl-6-fluoro-2-(1H-pyrazol-1-yl)-N-(2,2,2-trifluoroethyl)pyrimidine-4-amine (Inventive Compound No. 0349)
    [0414] 0.2g (4.2 mmol) of potassium fluoride was added to 10 ml of a dimethylsulfoxide solution containing 0.7g (2.1 mmol) of 5-sec-butyl-6-chloro-2-(1H-pyrazol-1-yl)-N-(2,2,2-trifluoroethyl)pyrimidine-4-amine at room temperature and the mixture was stirred for 18 hours at 150°C. After confirming the completion of reaction, the reaction solution was poured into water and extracted with diethylether. The obtained organic layer was washed with water and then dried over anhydrous magnesium sulfate. The insolubles were separated by filtration and then the solvent was distilled off under reduced pressure. Thus obtained residue was purified by silica gel column chromatography to obtain 0.4g of 5-sec-butyl-6-fluoro-2-(1H-pyrazol-1-yl)-N-(2,2,2-trifluoroethyl)pyrimidine-4-amine as a pale yellow powder (yield: 58%).
    [0415] Melting Point (°C): 132 to 1341H-NMR Data (CDCl3/TMS δ (ppm)): 0.90 (t, 3H), 1.34 (d, 3H), 1.75 (m, 2H), 2.66 (m, 1H), 4.37 (m, 2H), 5.25 (br, 1H), 6.46 (t, 1H), 7.79 (d, 1H), 8.45 (d, 1H) [Example 9]Production of 5-sec-butyl-N,N-diethylamino-6-methyl-2-(1H-pyrazol-1-yl)pyrimidine-4-amine (Inventive Compound No. 0953)
    [0416] 0.9g (13.2 mmol) of diethylamine was added to 10 ml of an N,N-dimethylformamide solution containing 0.5g (2.0 mmol) of 5-sec-butyl-4-chloro-6-methyl-2-(1H-pyrazol-1-yl)pyrimidine at room temperature and the mixture was stirred for 2 days at 80°C. After confirming the completion of reaction, the reaction solution was poured into water and extracted with diethylether. The obtained organic layer was washed with water and then dried over anhydrous magnesium sulfate. The insolubles were separated by filtration and then the solvent was distilled off under reduced pressure. Thus obtained residue was purified by silica gel column chromatography to obtain 0.5g of 5-sec-butyl-N,N-diethylamino-6-methyl-2-(1H-pyrazol-1-yl)pyrimidine-4-amine as an orange oily substance (yield: 84%).
    [0417] Refractive Index (nD 20): 1.55601H-NMR Data (CDCl3/TMS δ (ppm)): 0.80 (t, 3H), 1.18 (t, 6H), 1.39 (d, 3H), 1.74 (m, 2H), 2.59 (s, 3H), 3.01 (m, 1H), 3.25 (m, 2H), 3.44 (m, 2H), 6.42 (t, 1H), 7.77 (d, 1H), 8.49 (d, 1H) [Example 10]Production of 5-sec-butyl-6-methylthio-2-(1H-pyrazol-1-yl)-N-(2,2,2-trifluoroethyl)pyrimidine-4-amine (Inventive Compound No. 0361)
    [0418] A sodium methylmercaptan solution (content: 15%, 157.3 mmol) was added to 100 ml of a tetrahydrofuran solution containing 10.5g (31.5 mmol) of 5-sec-butyl-6-chloro-2-(1H-pyrazol-1-yl)-N-(2,2,2-trifluoroethyl)pyrimidine-4-amine at room temperature and the mixture was stirred for 3 days. After confirming the completion of reaction, the reaction solution was poured into water and extracted with ethyl acetate. The obtained organic layer was washed with water and brine in this order and then dried over anhydrous magnesium sulfate. The insolubles were separated by filtration and then the solvent was distilled off under reduced pressure. Thus obtained residue was purified by silica gel column chromatography to obtain 10.6g of 5-sec-butyl-6-methylthio-2-(1H-pyrazol-1-yl)-N-(2,2,2-trifluoroethyl)pyrimidine-4-amine as a colorless transparent viscous substance (yield: 97.2%).
    [0419] Refractive Index (nD 20): 1.55591H-NMR Data (CDCl3/TMS δ (ppm)): 0.91 (t, 3H), 1.32 (d, 3H), 1.73 (m, 2H), 2.62 (s, 3H), 3.14 (br, 1H), 4.38 (m, 2H), 4.88 (br, 1H), 6.44 (t, 1H), 7.80 (s, 1H), 8.52 (d, 1H) [Example 11]Production of 5-sec-butyl-6-methylsulfonyl-2-(1H-pyrazol-1-yl)-N-(2,2,2-trifluoroethyl)pyrimidine-4-amine (Inventive Compound No. 0363)
    [0420] 16.6g of m-chloroperbenzoic acid (purity: 70%, 67.5 mmol) was added to 100 ml of a chloroform solution containing 10.6g (30.7 mmol) of 5-sec-butyl-6-methylthio-2-(1H-pyrazol-1-yl)-N-(2,2,2-trifluoroethyl)pyrimidine-4-amine under ice cooling and the mixture was stirred for 30 minutes. Then, the mixture was further stirred overnight at room temperature. After confirming the completion of reaction, the reaction solution was poured into water and extracted with chloroform. The obtained organic layer was washed with an aqueous solution of sodium bisulfite, water, an aqueous sodium bicarbonate solution, water and brine in this order and then dried over anhydrous magnesium sulfate. The insolubles were separated by filtration and then the solvent was distilled off under reduced pressure. Thus obtained residue was purified by silica gel column chromatography to obtain 9.2g of 5-sec-butyl-6-methylsulfonyl-2-(1H-pyrazol-1-yl)-N-(2,2,2-trifluoroethyl)pyrimidine-4-amine as a white crystal (yield: 79.3%).
    [0421] Melting Point (°C): 52 to 551H-NMR Data (CDCl3/TMS δ (ppm)): 0.96 (t, 3H), 1.38 (d, 3H), 1.77 (m, 2H), 3.46 (s, 3H), 4.02 (m, 1H), 4.45 (m, 2H), 5.48 (br, 1H), 6.49 (t, 1H), 7.83 (s, 1H), 8.42 (d, 1H) [Example 12]Production of 6-benzyloxy-5-sec-butyl-2-(1H-pyrazol-1-yl)-N-(2,2,2-trifluoroethyl)pyrimidine-4-amine (Inventive Compound No. 0357)
    [0422] A mixture of 1.6g (4.2 mmol) of 5-sec-butyl-6-methylsulfonyl-2-(1H-pyrazol-1-yl)-N-(2,2,2-trifluoroethyl)pyrimidine-4-amine, 0.7g (6.4 mmol) of sodium bicarbonate and 10 ml of benzyl alcohol was stirred for 12 hours at 150°C. After confirming the completion of reaction, the reaction solution was poured into water and extracted with ethyl acetate. The obtained organic layer was washed with water and brine in this order and then dried over anhydrous magnesium sulfate. The insolubles were separated by filtration and then the solvent was distilled off under reduced pressure. Thus obtained residue was purified by silica gel column chromatography to obtain a mixture of 6-benzyloxy-5-sec-butyl-2-(1H-pyrazol-1-yl)-N-(2,2,2-trifluoroethyl)pyrimidine-4-amine and benzyl alcohol. [Example 13]Production of 5-sec-butyl-2-(1H-pyrazol-1-yl)-6-(2,2,2-trifluoroethylamino)pyrimidin-4-ol (Inventive Compound No. 0353)
    [0423] The mixture of 6-benzyloxy-5-sec-butyl-2-(1H-pyrazol-1-yl)-N-(2,2,2-trifluoroethyl)pyrimidine-4-amine and benzyl alcohol, which was obtained in Example 12, was dissolved in 20 ml of methanol and 0.1g of palladium carbon was added at room temperature. A hydrogen gas was supplied to the reaction solution under normal pressure and the solution was stirred overnight at room temperature. After confirming the completion of reaction, the insolubles were separated by filtration. After concentrating thus obtained filtrate, water was added and extraction with ethyl acetate was subjected. The obtained organic layer was dried over anhydrous magnesium sulfate. The insolubles were separated by filtration and then the solvent was distilled off under reduced pressure. Thus obtained residue was purified by silica gel column chromatography to obtain 0.8g of 5-sec-butyl-2-(1H-pyrazol-1-yl)-6-(2,2,2-trifluoroethylamino)pyrimidin-4-ol as a white powder (yield: 64.9%).
    [0424] Melting Point (°C) : 141 to 1431H-NMR Data (CDCl3/TMS δ (ppm)): 0.90 (t, 3H), 1.31 (d, 3H), 1.70 (m, 1H), 1.86 (m, 1H), 2.82 (br, 1H), 4.22 (m, 2H), 4.84 (br, 1H), 6.51 (s, 1H), 7.74 (d, 1H), 8.33 (d, 1H) [Example 14]Production of 5-sec-butyl-6-difluoromethoxy-2-(1H-pyrazol-1-yl)-N-(2,2,2-trifluoroethyl)pyrimidine-4-amine (Inventive Compound No. 0358)
    [0425] 0.4g (3.0 mmol) of anhydrous potassium carbonate was added to 10 ml of an N,N-dimethylformamide solution containing 0.63g (2.0 mmol) of 5-sec-butyl-2-(1H-pyrazol-1-yl)-6-(2,2,2-trifluoroethylamino)pyrimidin-4-ol at room temperature. At 50°C, the mixture was stirred for 1 hour while introducing an excessive amount of chlorodifluoromethane to the reaction solution. After confirming the completion of reaction, the reaction solution was poured into water and extracted with ethyl acetate. The obtained organic layer was washed with water and brine in this order and then dried over anhydrous magnesium sulfate. The insolubles were separated by filtration and then the solvent was distilled off under reduced pressure. Thus obtained residue was purified by silica gel column chromatography to obtain 0.35g of 5-sec-butyl-6-difluoromethoxy-2-(1H-pyrazol-1-yl)-N-(2,2,2-trifluoroethyl)pyrimidine-4-amine as a white powder (yield: 47.9%).
    [0426] Melting Point (°C): 94 to 951H-NMR Data (CDCl3/TMS δ (ppm)): 0.88 (t, 3H), 1.33 (d, 3H), 1.76 (m, 2H), 2.83 (m, 1H), 4.37 (m, 2H), 5.24 (br, 1H), 6.45 (dd, 1H), 7.64 (t, 1H, J=72.5 Hz), 7.80 (d, 1H), 8.43 (d, 1H) [Example 13]Production of ethyl 5-amino-1-[5-sec-butyl-4-chloro-6-(2,2,2-trifluoroethylamino)pyrimidin-2-yl]-1H-pyrazol-4-carboxylate (Inventive Compound No. 0601)
    [0427] 0.6g (3.8 mmol) of ethyl ethoxymethylenecyanoacetate was added to 10 ml of an ethanol solution containing 1.0g (3.2 mmol) of 5-sec-butyl-6-chloro-2-hydrazinyl-N-(2,2,2-trifluoroethyl)pyrimidine-4-amine at room temperature and the mixture was stirred for 27 hours under reflux. After confirming the completion of reaction, the solvent was distilled off under reduced pressure. The reaction solution was poured into water and extracted with ethyl acetate. The obtained organic layer was washed with water and then dried over anhydrous magnesium sulfate. The insolubles were separated by filtration and then the solvent was distilled off under reduced pressure. Thus obtained residue was purified by silica gel column chromatography to obtain 0.9g of ethyl 5-amino-1-[5-sec-butyl-4-chloro-6-(2,2,2-trifluoroethylamino)pyrimidin-2-yl]-1H-pyrazol-4-carboxylate as a white powder (yield: 63%).
    [0428] Melting Point (°C): 173 to 1741H-NMR Data (CDCl3/TMS δ (ppm)): 0.91 (t, 3H), 1.34-1.39 (m, 6H), 1.73-1.78 (m, 2H), 3.39 (br, 1H), 4.26-4.44 (m, 4H), 5.27 (br, 1H), 7.29 (br, 2H), 7.82 (s, 1H) [Example 16]Production of 5-sec-butyl-6-chloro-2-(4-chloro-1H-pyrazol-1-yl)-N-(2,2,2-trifluoroethyl)pyrimidine-4-amine (Inventive Compound No. 0434)
    [0429] 0.4g (3.3 mmol) of N-chlorosuccinimide was added to 10 ml of an acetonitrile solution containing 1.0g (3.0 mmol) of 5-sec-butyl-6-chloro-2-(1H-pyrazol-1-yl-)-N-(2,2,2-trifluoroethyl)pyrimidine-4-amine at room temperature and the mixture was stirred for 2 hours under reflux. After confirming the completion of reaction, the reaction solution was poured into water and extracted with ethyl acetate. The obtained organic layer was washed with water and then dried over anhydrous magnesium sulfate. The insolubles were separated by filtration and then the solvent was distilled off under reduced pressure. Thus obtained residue was purified by silica gel column chromatography to obtain 0.8g of 5-sec-butyl-6-chloro-2-(4-chloro-1H-pyrazol-1-yl)-N-(2,2,2-trifluoroethyl)pyrimidine-4-amine as a white powder (yield: 76%).
    [0430] Melting Point (°C) : 173 to 1741H-NMR Data (CDCl3/TMS δ (ppm)): 0.91 (t, 3H), 1.35 (d, 3H), 1.75 (m, 2H), 3.40 (br, 1H), 4.35 (m, 2H), 5.28 (br, 1H), 7.71 (s, 1H), 8.42 (s, 1H) [Example 17]Production of 5-sec-butyl-N-(1-methylethyl)-2-(1H-pyrazol-1-yl)-6-trifluoromethylpyrimidine-4-amine (Inventive Compound No. 0240)
    [0431] 0.4g (4.0 mmol) of isopropylamine hydrochloride and 0.4g (4.0 mmol) of triethylamine were added to 20 ml of a tetrahydrofuran solution containing 0.4g (1.3 mmol) of 5-sec-butyl-4-chioro-2-(1H-pyrazol-1-yl)-6-trifluoromethylpyrimidine that can be obtained in Reference Example 19 which will be described below, at room temperature and the mixture was stirred overnight at 60°C. After confirming the completion of reaction, the reaction solution was poured into water and extracted with ethyl acetate. The obtained organic layer was washed with water and then dried over anhydrous magnesium sulfate. The insolubles were separated by filtration and then the solvent was distilled off under reduced pressure. Thus obtained residue was dissolved in 20 ml of ethanol and 0.2g (2.4 mmol) of anhydrous sodium acetate and 40mg of 10% palladium carbon were added thereto. A hydrogen gas was supplied under normal pressure and the mixture was stirred overnight at room temperature. After confirming the completion of reaction, the catalyst was removed by filtration and thus obtained filtrate was concentrated. Water was added to the residue and it was extracted with ethyl acetate. The obtained organic layer was dried over anhydrous magnesium sulfate. The insolubles were separated by filtration and then the solvent was distilled off under reduced pressure. Thus obtained residue was purified by silica gel column chromatography to obtain 0.26g of 5-sec-butyl-N-(1-methylethyl)-2-(1H-pyrazol-1-yl)-6-trifluoromethylpyrimidine-4-amine as a colorless crystal (yield: 59%).
    [0432] Melting Point (°C): 85 to 871H-NMR Data (CDCl3/TMS δ (ppm)): 0.89 (t, 3H), 1.32 (d, 9H), 1.73 (m, 2H), 3.25 (m, 1H), 4.54 (m, 1H), 5.06 (br, 1H), 6.43 (dd, 1H), 7.80 (d, 1H), 8.52 (d, 1H) [Example 18]Production of 5-sec-butyl-6-ethyl-2-(1H-pyrazol-1-yl)-N-(2,2,2-trifluorcethyl)pyrimidine-4-amine (Inventive Compound No. 0385)
    [0433] 0.4g (6.6 mmol) of 1H-pyrazole and 0.9g (6.6 mmol) of potassium carbonate were added to 30 ml of an N,N-dimethylformamide solution containing 1.1g (3.3 mmol) of 5-sec-butyl-6-ethyl-2-methylsulfonyl-N-(2,2,2-trifluoroethyl)pyrimidine-4-amine at room temperature and the mixture was stirred for 4 days at 80°C. After confirming the completion of reaction, the reaction solution was poured into water and extracted with ethyl acetate. The obtained organic layer was washed with water and then dried over anhydrous magnesium sulfate. The insolubles were separated by filtration and then the solvent was distilled off under reduced pressure. Thus obtained residue was purified by silica gel column chromatography to obtain 1.0g of 5-sew-butyl-6-ethyl-2-(1H-pyrazol-1-yl)-N-(2,2,2-trifluoroethyl)pyrimidine-4-amine as a white powder (yield: 89%).
    [0434] Melting Point (°C): 89 to 901H-NMR Data (CDCl3/TMS δ (ppm)): 0.91 (t, 3H), 1.26-1.35 (m, 6H), 1.66-1.78 (m, 2H), 2.76-2.89 (m, 2H), 3.10 (br, 1H), 5.00 (br, 1H), 6.43 (t, 1H), 7.78 (d, 1H), 8.51 (d, 1H) [Example 19]Production of 6-bromo-5-sec-butyl-2-(1H-pyrazol-1-yl)-N-(2,2,2-trifluoroethyl)pyrimidine-4-amine (Inventive Compound No. 0351)
    [0435] 0.5g (7.1 mmol) of 1H-pyrazole and 1.6g (11.9 mmol) of anhydrous potassium carbonate were added to 30 ml of an N,N-dimethylformamide solution containing 2.3g (5.9 mmol) of 6-bromo-5-sec-butyl-2-methylsulfonyl-N-(2,2,2-trifluoroethyl)pyrimidine-4-amine at room temperature and the mixture was stirred for 24 hours at 50°C. After confirming the completion of reaction, the reaction solution was poured into water and extracted with ethyl acetate. The obtained organic layer was washed with water and then dried over anhydrous magnesium sulfate. The insolubles were separated by filtration and then the solvent was distilled off under reduced pressure. Thus obtained residue was purified by silica gel column chromatography to obtain 1.4g of 6-bromo-5-sec-butyl-2-(1H-pyrazol-1-yl)-N-(2,2,2-trifluoroethyl)pyrimidine-4-amine as a white powder (yield: 62%).
    [0436] Melting Point (°C): 136 to 1391H-NMR Data (CDCl3/TMS δ (ppm)): 0.93 (t, 3H), 1.33 (d, 3H), 1.69-1.79 (m, 2H), 3.50 (br, 1H), 4.32-4.43 (m, 2H), 5.22 (br, 1H), 6.45 (q, 1H), 7.79 (d, 1H), 8.45 (d, 1H) [Example 20]Production of 5-sec-butyl-6-cyclopropyl-2-(1H-pyrazol-1-yl)-N-(2,2,2-trifluoroethyl)pyrimidine-4-amine (Inventive Compound No. 0387)
    [0437] 0.1g (0.1 mmol) of tetrakis(triphenylphosphine)palladium, 0.2g (2.0 mmol) of cyclopropylboronic acid, 0.3g (2.5 mmol) of anhydrous sodium carbonate and 5 ml of water were added to 20 ml of a toluene solution containing 0.6g (1.7 mmol) of 5-sec-butyl-6-bromo-2-(1H-pyrazol-1-yl)-N-(2,2,2-trifluoroethyl)pyrimidine-4-amine and the mixture was stirred for 26 hours under reflux. The reaction solution was poured into water and extracted with ethyl acetate. The obtained organic layer was washed with water and then dried over anhydrous magnesium sulfate. The insolubles were separated by filtration and then the solvent was distilled off under reduced pressure. Thus obtained residue was purified by silica gel column chromatography to obtain 0.3g of 5-sec-butyl-6-cycloprapyl-2-(1H-pyrazol-1-yl)-N-(2,2,2-trifluoroethyl)pyrimidine-4-amine as a pale yellow powder (yield: 49%).
    [0438] Melting Point (°C): 84 to 851H-NMR Data (CDCl3/TMS δ (ppm) : 0.89-1.03 (m, 5H), 1.18-1.37 (m, 5H), 1.73-1.83 (m, 2H), 2.10-2.19 (m, 1H), 3.30 (br, 1H), 4.37-4.43 (m, 2H), 4.98 (br, 1H), 6.40 (t, 1H), 7.77 (t, 1H), 8.47 (d, 1H) [Example 21]Production of 5-sec-butyl-N4, N4-diethyl-2-(1H-pyrazol-1-yl)-N6-(2,2,2-trifluoroethyl)pyrimidine-4,6-diamine (Inventive Compound No. 0371)
    [0439] 0.3g (2.4 mmol) of anhydrous potassium carbonate and 0.1g (1.6 mmol)) of 1H-pyrazole were added to 10 ml of 1,3-dimethyl-2-imidazolidinone solution containing 0.6g (1.6 mmol) of 5-sec-butyl-N4,N4-diethyl-2-methylsulfonyl-N6-(2,2,2-trifluoroethyl)pyrimidine-4,6-diamine and the mixture was stirred for 6 hours at 150°C. After confirming the completion of reaction, the reaction solution was poured into water and extracted with ethyl acetate. The obtained organic layer was washed with water and then dried over anhydrous magnesium sulfate. The insolubles were separated by filtration and then the solvent was distilled off under reduced pressure. Thus obtained residue was purified by silica gel column chromatography to obtain 0.2g of 5-sec-butyl-N4,N4-diethyl-2-(1H-pyrazol-1-yl)-N6-(2,2,2-trifluoroethyl)pyrimidine-4,6-diamine as a yellowish brown viscous liquid (yield: 38%).
    [0440] Refractive Index (nD 20):1.52801H-NMR Data (CDCl3/TMS δ (ppm)): 0.83 (t, 3H), 1.14 (t, 6H), 1.34 (d, 3H), 1.66 (m, 2H), 3.15 (m, 2H), 3.36 (m, 2H), 4.49-4.28 (m, 2H), 4.79 (br, 1H), 6.40 (m, 1H), 7.78 (d, 1H), 8.49 (d, 1H)
    [0441] Next, physical properties of the compounds of present application synthesized according to above-mentioned Examples 1 to 21 are shown in Tables 41 to 50.
    [0442] [Table 41]Compound No.M.P. (°C) OR R.I.(nD 20)0002M.P.146-1480006M.P.141-1440009M.P.42-440010M.P.78-800013M.P.53-540014M.P.91-920018M.P.131-1330022M.P.148-1510025R.I.1.57580026R.I.1.58880029R.I.1.58700030M.P.90-910035M.P.140-1420047M.P.149-1510049M.P.140-1420133M.P.64-650135R.I.1.57660147M.P.89-900149M.P.107-1080155M.P.175-1780159M.P.139-1410162R.I.1.56910163M.P.63-650166M.P.55-560167M.P.78-790171M.P.168-1690175M.P.120-1230178R.I.1.56310179M.P.41-420182R.I.1.56990183R.I.1.56960186R.I.1.55420187M.P.132-1330190R.I.1.57170191M.P.164-1650194M.P.105-1070195M.P.138-140 M.P.: Melting PointR.I.: Refractive Index
    [0443] [Table 42]Compound No.M.P.(°C) OR R.I.(nB 20)0198M.P.110-1110199M.P.150-1510200R.I.1.57090211R.I.1.57400222M.P.116-1170240M.P.85-870241M.P.120-1210242M.P.106-1070245R.I.1.54490246M.P.48-500249M.P.99-1010250M.P.113-1140253M.P.88-900254R.I.1.56680259M.P.93-950300R.I.1.55550301R.I1.56420304M.P.91-930305R.I.1.56080308M.P.89-900309R.I.1.56390312R.I.1.53350313R.I.1.55870316M.P.104-1070317M.P.125-1270325R.I.1.55690328M.P.138-1390329M.P.117-1190332M.P.110-1120333M.P.93-950336M.P.87-900337M.P.107-1090341M.P.114-1170348M.P.147-1490349M.P.132-1340350M.P.137-1390351M.P.136-139 M.P.: Melting PointR.I.: Refractive Index
    [0444] [Table 43]Compoun No.M.P. (°C) 0R R.I. (nD 20)0353M.P.141-1430354M.P.95-960355M.P.97-980358M.P.94-950360M.P.104-1050361R.I.1.55590363M.P.52-550367R.I.1.53120368R.I.1.52890370M.P.97-990371R.I.1.52800372M.P.193-1950374M.P.102-1030376M.P.178-1800377M.P.124-1270379M.P.173-1740380M.P.84-850381M.P.92-940382M.P.88-900383R.I.1.52360384R.I.1.53420385M.P.89-900386M.P.94-960387M.P.84-850389M.P.50-520391M.P.109-1100392M.P.141-1430393M.P.47-480394M.P.67-700395M.P.87-890401M.P.189-1910403M.P.177-1780410M.P.154-1550422M.P.198-2000434M.P.173-1740435M.P.157-1600436M.P.170-172 M.P.: Melting PointR.I.: Refractive Index
    [0445] [Table 44]Compound No.M.P. (°C) OR R.I. (nD 20)0437M.P.180-1820462M.P.133-1340489M.P.143-1440504M.P.213-2160507M.P.181-1820508M.P.192-1930510M.P.189-1900628M.P.253-2550536M.P.203-2060601M.P.173-1740614M.P.188-1890710M.P.50-520721R.I.1.54580723M.P.111-1130732M.P.58-600764M.P.50-620768M.P.150-1530772M.P.83-850775M.P.101-1020776M.P.97-990780R.I.1.57810784M.P.33-350791M.P.78-790792M.P.77-790796R.I.1.56430799R.I.1.56090800R.I.1.56470812M.P.81-830816M.P.57-590820M.P.103-1050824M.P.176-1770828M.P.173-1740836R.I.1.55660840R.I.1.55110844R.I.1.54320860M.P.109-1110864M.P.99-100 M.P.: Melting PointR.I.: Refractive Index
    [0446] [Table 45]Compound NoM.P. (°C) OR R.I. (DD 20)0868M.P.181-1830900R.I.1.58220901R.I.1.56780902R.I.1.57200903M.P.137-1380904M.P.115-1160906M.P.95-980907R.I.1.57600908R.I.1.58620911R.I.1.57420912M.P.88-900913M.P.143-1440015R.I.1.56500916R.I.1.57340919R.I.1.56150920R.I.1.54610921R.I.1.56810934M.P.87-880943M.P.95-980953R.I.1.55600961R.I.1.52730962R.I.1.55850963R.I.1.57550966R.I.1.55000967R.I.1.56420970R.I.1.54680971R.I.1.56300974M.P.98-990975R.I.1.56740979R.I.1.55560986R.I.1.54980987R.I.1.56400990R.I.1.54070991R.I.1.55730994R.I.1.54270996R.I.1.55380998M.P.65-67 M.P.: Melting PointR.I.: Refractive Index
    [0447] [Table 46]Compound No.M.P. (°C) OR R.I. (RD 20)1000M.P.79-811008M.P.33-361030M.P.111-1131031M.P.131-1321058R.I.1.57301060R.I.1.57181061R.I.1.56311062M.P.87-901064R.I.1.55631065R.I.1.56701068M.P.134-1361070R.I.1.56711071M.P.123-1251074R.I.1.55281075M.P.78-791079R.I.1.56611081M.P.100-1021082M.P.86-881085R.I.1.56761086R.I.1.56521087R.I.1.57531089R.I.1.56291090M.P.87-901093R.I.1.55621094R.I.1.56451097M.P.61-631098R.I.1.58931101M.P.70-711102R.I.1.58101106M.P.133-1351110M.P.102-1041115M.P.96-981160R.I.1.52471163M.P.129-1301167M.P.89-911175R.I.1.60731178M.P.61-64 M.P.: Melting PointR.I.: Refractive Index
    [0448] [Table 47]Compound NoM.P.(°C) OR R.I. (nD 20)1179M.P.99-1011182R.I.1.56171183R.I.1.56711186R.I.1.55981187R.I.1.56501190R.I.1.55651191R.I.1.55331192R.I.1.57211193R.I.1.58881195M.P.147-1491196R.I.1.55031197R.I.1.54651199M.P.90-931204M.P.69-711211R.I.1.56211216R.I1.57001222M.P.160-1621225R.I.1.55811233R.I.1.53441239R.I.1.56901243R.I.1.56231247R.I.1.52511254R.I.1.57071255R.I.1.57291259R.I.1.56101263R.I.1.60001267M.P.65-681271M.P.89-921275R.I.1.57411279M.P.152-1531283M.P.121-1241286R.I.1.56001287R.I.1.57071290R.I.1.56531291M.P.66-681311M.P.83-851315M.P.168-169 M.P.: Melting PointR.I.: Refractive Index
    [0449] [Table 48]Compound No.M.P. (°C) OR R.I. (nD 20))1318R.I.1.55571319R.I.1.56291322M.P.56-581323R.I.1.57411328M.P.103-1041342M.P.103-1051426M.P.65-671428R.I.1.56701440M.P.61-631442M.P.71-721448M.P.127-1281462M.P.81-831455R.I.1.55131466R.I.1.57311459M.P.64-661460M.P.93-951497M.P.111-1131511M.P.152-1551633M.P.183-1841664M.P.68-701576M.P.83-861595M.P.55-571597M.P.94-961609M.P.80-831611M.P.91-931617M.P.141-1431624R.I.1.57281625R.I.1.57601628M.P.117-1191629M.P.118-1191633M.P.123-1261637M.P.146-1471640R.I.1.57001641R.I.1.58301644R.I.1.57981645R.I.1.58771651R.I.1.5513 M.P.: Melting PointR.I.: Refractive Index
    [0450] [Table 49]Compound No.M.P. (°C) OR R.I. (nD 20)1661M.P.119-1221737M.P.106-1081829M.P.151-1521833R.I.1.62171845M.P.118-1201849R.I.1.59171850M.P.141-1431862M.P.96-981898R.I.1.60521906M.P.107-1091914R.I.1.59041918M.P.55-571994R.I.1.58031996M.P.163-1702011M.P.95-970398M.P.145-1460454M.P.144-1450455M.P.81-830458M.P.168-1690459M.P.125-1270461M.P.253-2550464M.P.249-2500465M.P.123-1250481M.P.175-1780505M.P.203-2040509M.P.157-1600511M.P.55-580529M.P.188-1900531M.P.147-1490533M.P.202-2040537M.P.168-1700538M.P.174-1760539M.P.107-1100548M.P.180-1810555M.P.163-1640556M.P.165-1670557M.P.1.47940615M.P.46-490698M.P.193-1940702M.P.221-2221958R.I.1.5581 M.P.: Melting PointR.I.: Refractive Index
    [0451] [Table 50]Compound No. 1H-NMR data(CDCl3/TMS δ(ppm))02320.88(t, 3H, J=7.4Hz), 1.26-1.31(m, 3H), 1.65-1.79(m,2H), 2.48(s, 3H), 4.35-4.50(m, 1H), 4.63(br, 1H), 6.39-6.41(m, 1H), 7.76-7.76(m, 1H), 8.49-8.58(m, 1H)03730.88(t, 3H, J=7.4Hz), 1.34(d, 3H, J=7.2Hz), 1.63-1.79(m, 2H), 4.10-4.15(m, 1H). 4.37-4.46(m, 2H), 6.45(br, 1H), 6.49-6.50(m, 1H), 7.84(s, 1H), 8.53(d, 1H, J=2.8Hz)07080.91-0.97(m,3H), 1.28-1.32(m, 3H), 1.47(d, 3H, J=6.9Hz), 1.62-1.78(m, 2H), 2.43-2.63(m, 1H), 4.79-4.83(br, 1H), 5.22- 5.35(m, 2H), 6.46-6.45(m, 1H), 7.79(s, 1H), 8.48(d.,1H, J=2.1Hz)07600.89(3H, t, J=7.6Hz), 1.31(3H, d, J=7.3Hz), 1.69-1.73(2H, m), 2.49-2.60(2H, m), 3.34-3.51(1H, br), 3.89-3.93(2H, m), 5.34(1H, br), 6.44-6.45(1H, m), 7.78(1H, t), 8.45-8.49(1H. m)07880.91(3H. t, J=7.3Hz 1.33(3H, d, J=7.2 Hz), 1.69-1.78(2H, m), 3.36(1H, brs), 3.78(2H, dt, J=9.1, 5.2 Hz), 3.89(3H, t, J=4.8 Hz), 5.60(1.H, br), 6.43(1H, dd, J=2.5, 1.7Hz), 7.77(1H, a), 8.47(1H, d, J=2.2Hz,)08270.91(3H, t, J=7.3Hz), 1.26(3H, d, J=6.8Hz), 1.58-1.77(2H, m), 2.48-2.57(1H, m), 2.67(2H, t, J=6.1Hz), 3.86-3.93(2H, m), 5.69(1H, br), 6.44-6.47(1H, m), 7.77(1H, t), 8.08(1H, s), 8.47(1H, d)11550.91(3H, t, J=7.4 Hz), 1.30(3H, d, J=7.7 Hz), 1.58-1.71(2H, m), 2.39-2.53(2H, m), 2.88-2.94(1H, m), 3.95-4.09(4H, m), 6.44(1H, s), 7.79(1H, s), 8.25(1H, s), 8.48(1H, d, J=2.5 Hz)11560.83(3H, t, J=7.5 Hz, 1.48(3H, J=7.1 Hz), 1.88-1.97(2H, m), 2.39-2.49(2H, m), 2.83-2.92(m, m), 3.80-3.93(m, m), 3.98-4.17(2H, m, 6.45(1H, dd, J=2.6 1.6 Hz), 7.79(1H, d, J=0.5 Hz), 8.46(1H, d, J=2.7 Hz)11590.92(3H, t, J=7.4 Hz), 1.82(3H, d, J=6.8 Hz), 1.58-1.75(2H, m), 2.77-1159 2.83(1H, m), 4.09-4.30(4H, m), 6.46(1H, d, J=2.5 Hz, 7.81(1H, s), 8.33(1H, s), 8.47(1H, d, J=2.5 Hz)12060.85(3H, t, J=7.4Hz), 1.01(3H, d J=6.3Hz, 1.35-1.43(2H,m), 1.53(3H, d) 1206 J=7.1Hz), 1.61-1.81(3H, m), 1.88-1.98(2H,m), 2.99-3.07(2H, m), 3.24-3.33(1H, m), 3.45(3H, s), 3.85(2H, m), 6.46-6.48(1H, m), 7.82(1H, s), 8.44(1H, d, J=2.2Hz) (Intermediate Production Method)<Reference Example 1>Production of 5-sec-butyl-2-mercaptopyrimidine-4,6-diol
    [0452] 69.2g (203.4 mmol) of a 20% sodium ethoxide-ethanol solution was added to 100 ml of an ethanol solution containing 20.0g (92.5 mmol) of diethyl sec-butylmalonate and 7.7g (101.7 mmol) of thiourea at room temperature and the mixture was stirred under reflux for 6 hours. A 5-sec-butyl-2-mercaptopyrimidine-4,6-diol production was confirmed with a gas chromatograph and a gas chromatograph mass spectrometer. <Peference Example 2>Production of 5-sec-b-butyl-2-methylthiopyrimidine-4,6-diol
    [0453] 14.4g (101.7 mmol) of methyl iodide was added to the reaction solution of Reference Example 1 at room temperature and the mixture was stirred for 14 hours at room temperature. After confirming the completion of reaction, the solvent was distilled off under reduced pressure. To the obtained residue, water was added and pH was adjusted to 2 using concentrated hydrochloric acid. A precipitated crystal was filtered, washed with water and then dried to obtain 17.5g of 5-sec-butyl-2-methylthiopyrimidine-4,6-diol as a milky white crystal (yield: 88%).
    [0454] 1H-NMR Data (DMSO-d6/TMS δ (ppm)): 0.73 (3H, t, J=7.4 Hz), 1.11 (3H, d, J=7.1 Hz), 1.39-1.53 (1H, m), 1.62-1.77 (1H, m), 2.46 (3H, s), 2.74-2.86 (1H, m), 11.5 (2H, br). <Reference Example 3>Production of 5-sec-butyl-4,6-dichloro-2-methylthiopyrimidine
    [0455] 11.5g (74.9 mmol) of phosphorus oxychloride and 3.0g (24.9 mmol) of N,N-dimethylaniline were added to 5.0g (25.0 mmol) of 5-sec-butyl-2-methylthiopyrimidine-4,6-diol and the mixture was stirred for 2 hours at 100°C. After confirming the completion of reaction, the reaction solution was poured into water and extracted with dichloromethane. The obtained organic layer was washed with water and then with a saturated aqueous sodium bicarbonate solution and dried over anhydrous magnesium sulfate. The insolubles were separated by filtration and then the solvent was distilled off under reduced pressure, to obtain 5.9g of 5-sec-butyl-4,6-dichloro-2-methylthiopyrimidine (yield: 99%).
    [0456] 1H-NMR Data (CDCl3/TMS δ (ppm)): 0.86 (3H, t, J=7.4 Hz), 1.36 (3H, d, J=7.1 Hz)), 1.67-1.83 (1H, m), 1.89-2.04 (1H, m), 2.55 (3H, s), 3.38-3.51 (1H, m) <Reference Example 4>Production of 5-sec-butyl-4-chloro-6-(4-methylpiperidin-1-yl)-2-methylthiopyrimidine
    [0457] 4.0g (39.2 mmol) of triethylamine was added to 35 ml of a tetrahydrofuran solution containing 4.5g (17.8 mmol) of 5-sec-butyl-4,6-dichloro-2-methylthiopyrimidine. Thereto, 1.9g (19.6 mmol) of 4-methylpiperidine was further added under ice cooling and the mixture was stirred for 14 hours at room temperature. After confirming the completion of reaction, the reaction solution was poured into water and extracted with ethyl acetate. The obtained organic layer was washed with 5% hydrochloric acid, a saturated aqueous sodium bicarbonate solution and a saturated aqueous sodium chloride solution and then dried over anhydrous magnesium sulfate. The insolubles were separated by filtration and then the solvent was distilled off under reduced pressure, to obtain 5.7g of 5-sec-butyl-4-ohloro-6-(4-methylpiperidin-1-yl)-2-methylthiopyrimidine as a pale yellow viscous substance (yield: quantitative).
    [0458] Refractive Index (nD 20): 1.55371H-NMR Data (CDCl3/TMS δ (ppm)): 0.81 (3H, t, J=7.4 Hz), 0.98 (3H, d, J=6.6 Hz), 1.25-1.40 (5H, m), 1.57-1.90 (5H, m), 2.50 (3H, s), 2.75-2.95 (3H, m), 3.58-3.63 (2H, m) <Reference Example 5>Production of 5-sec-butyl-4-chloro-6-(4-methylpiperidin-1-yl)-2-methylsulfonylpyrimidine
    [0459] 9.2g of m-chloroperbenzoic acid (purity: 70%, 53.4 mmol) was added to 200 ml of a dichloromethane solution containing 5.7g (17.8 mmol) of 5-sec-butyl-4-chloro-6-(4-methylpiperidin-1-yl)-2-methylthiopyrimidine under ice cooling and the mixture was stirred for 30 minutes. Then, the mixture was further stirred for 7 hours at room temperature. After confirming the completion of reaction, the reaction solution was poured into water and extracted with dichloromethane. The obtained organic layer was washed with an aqueous solution of sodium bisulfite, water, an aqueous sodium bicarbonate solution and brine in this order and then dried over anhydrous magnesium sulfate. The insolubles were separated by filtration and then the solvent was distilled off under reduced pressure. Thus obtained residue was purified by silica gel column chromatography to obtain 5.9g of 5-sec-butyl-4-chloro-6-(4-methylpiperidin-1-yl)-2-methylsulfonylpyrimidine as a white powder (yield: 96%).
    [0460] Melting Point (°C) : 88 to 901H-NMR Data (CDCl3/TMS δ (ppm)): 0.84 (3H, t, J=7.4 Hz), 1.00 (3H, d, J=6.6 Hz), 1.22-1.45 (5H, m), 1.56-1.96 (5H, m), 2.77-2.85 (1H, m), 2.94-3.06 (2H, m), 3.29 (3H, s), 3.79-3.83 (2H, m) <Reference Example 6>Production of dimethyl 2-[5-sec-butyl-6-(4-methylpiperidin-1-yl)-2-(1H-pyrazol-1-yl)pyrimidin-4-yl]malonate
    [0461] 1.1g (8.5 mmol) of dimethyl malonate was added to 20 ml of a tetrahydrofuran solution containing 0.3g of sodium hydride (purity: 60%, 6.4 mmol) under ice cooling and the mixture was stirred for 1 hour at room temperature. Thereto, 10 ml of a tetrahydrofuran solution containing 1.6g (4.2 mmol) of 5-sec-butyl-6-(4-methylpiperidin-1-yl)-4-methylsulfonyl-2-(1H-pyrazol-1-yl)pyrimidine was further added dropwise under ice cooling. Thereafter, the mixture was stirred for 5 hours at 80°C. After confirming the completion of reaction, the reaction solution was poured into water and extracted with ethyl acetate. The obtained organic layer was washed with water and then dried over anhydrous magnesium sulfate. The insolubles were separated by filtration and then the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography to obtain 1.8g of dimethyl 2-[5-sec-butyl-6-(4-methylpiperidin-1-yl)-2-(1H-pyrazol-1-yl)pyrimidin-4-yl]malonate (yield: quantitative).
    [0462] 1H-NMR Data (CDCl3/TMS δ (ppm)): 0.88 (3H, t, J=7.5 Hz), 1.01 (3H, d, J=6.6 Hz),1.32-1.43 (4H, m), 1.51-1.95 (10H, m), 2.91-3.07 (2H, m), 3.58-3.71 (2H, m), 3.78 (3H, s), 5.12 (1H, s), 6.38-6.39 (1H, m), 7.78 (1H, s), 8.47 (1H, d, J=2.8 Hz) <Reference Example 7>Production of tert-butyl N-(5-sec-butyl-6-chloro-2-methylthiopyrimidon-4-yl)-N-2,2,2-trifluoroethylcarbamate
    [0463] 8.3g (41.6 mmol) of tert-butyl 2,2,2-trifluoroethylcarbamate was added to 40 ml of an N,N-dimethylformamide solution containing 1.3g of sodium hydride (purity: 60%, 33.3 mmol) under ice cooling and the mixture was stirred for 1 hour. Thereto, 7.0g (27.7 mmol) of 5-sec-butyl-4,6-dichloro-2-methylthiopyrimidine was further added at room temperature and the mixture was stirred overnight. After confirming the completion of reaction, the reaction solution was poured into water and extracted with ethyl acetate. The obtained organic layer was washed with water and then dried over anhydrous magnesium sulfate. The insoluble were separated by filtration and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography to obtain 7.2g of ter-butyl N-(5-sec-butyl-6-chloro-2-methylthiopyrimidin-4-yl)-N-2,2,2-trifluoroethylcarbamate as a pale orange oily substance (yield: 63%).
    [0464] Refractive Index (nD 20): 1.48881H-NMR Data (CDCl3/TMS δ (ppm)): 0.94 (br, 3H), 1.24-1.59 (m, 14H), 2.54 (s, 3H), 2.77 (br, 1H), 4.46 (br, 2H) <Reference Example 8>Production of 5-sec-butyl-6-chloro-2-methylthio-N-(2,2,2-trifluoroethyl)pyrimidine-4-amine
    [0465] 7.7g (67.3 mmol) of trifluoroacetic acid was added to 20 ml of a dichloromethane solution containing 3.7g (9.0 mmol) of tert-butyl N-(5-sec-butyl-6-chloro-2-methylthiopyrimidin-4-yl)-N-2,2,2-trifluoroethylcarbamate at room temperature and the mixture was stirred overnight. After confirming the completion of reaction, the reaction solution was poured into water and extracted with dichloromethane. The obtained organic layer was washed with water and then dried over anhydrous magnesium sulfate. The insolubles were separated by filtration and then the solvent was distilled off under reduced pressure. Thus obtained residue was purified by silica gel column chromatography to obtain 2.6g of 5-sec-butyl-6-chloro-2-methylthio-N-2,2,2-trifluoroethylpyrimidine-4-amine as a white powder (yield: 91%).
    [0466] Melting Point (°C): 82 to 831H-NMR Data (CDCl3/TMS δ (ppm)): 0.89 (t, 3H), 1.29 (d, 3H), 1.70 (m, 2H), 2.50 (s, 3H), 3.29 (br, 1H), 4.28 (m, 2H), 5.02 (br, 1H) <Reference Example 9>Production of 5-sec-butyl-6-chloro-2-methylsulfonyl-N-2,2,2-trifluoroethylpyrimidine-4-amine
    [0467] 7.9g of m-chloroperbenzoic acid (purity: 70%, 32.2 mmol) was added to 200 ml of a chloroform solution containing 2.9g (9.2 mmol) of 5-sec-butyl-6-chloro-2-methylthio-N-2,2,2-trifluoroethylpyrimidine-4-amine under ice cooling and the mixture was stirred for 30 minutes. Then, the mixture was further stirred for 1.5 hours at room temperature. After confirming the completion of reaction, the reaction solution was poured into water and extracted with dichloromethane. The obtained organic layer was washed with an aqueous solution of sodium bisulfite, water, an aqueous sodium bicarbonate solution and brine in this order and then dried over anhydrous magnesium sulfate. The insolubles were separated by filtration and then the solvent was distilled off under reduced pressure. Thus obtained residue was purified by silica gel column chromatography to obtain 2.74g of 5-sec-butyl-6-chloro-2-methylsulfonyl-N-2,2,2-trifluoroethylpyrimidine-4-amine as a white crystal (yield: 86%).
    [0468] Melting Point (°C): 107 to 1091H-NMR Data (CDCl3/TMS δ (ppm)): 0.92 (t, 3H), 1.35 (d, 3H), 1.77 (m, 2H), 3.29 (s, 3H), 3.44 (br, 1H), 4.34 (m, 2H), 5.42 (br, 1H) <Reference Example 10>Production of 5-sec-butyl-4-hydroxy-2-mercapto-6-methylpyrimidine
    [0469] To 100 my of an ethanol solution containing 2.7g (14.5 mmol) of ethyl 2-sec-butyl-3-oxobutanate synthesized according to a method disclosed in US No. 6348618 and 1.2g (15.9 mmol) of thiourea, 9.9g (29.0 mmol) of a 20% sodium ethoxide-ethanol solution was added at room temperature and the mixture was stirred for 4 hours under reflux. A 5-sec-butyl-4-hydroxy-2-mercapto-6-methylpyrimidine production was confirmed with a gas chromatograph and a gas chromatograph mass spectrometer. <Reference Example 11>Production of 5-sec-butyl-4-hydroxy-6-methyl-2-methylthiopyrimidine
    [0470] 2.3g (15.9 mmol) of methyl iodide was added to the reaction solution of Reference Example 10 at room temperature and the mixture was stirred for 24 hours at room temperature. After confirming the completion of reaction, the solvent was distilled off under reduced pressure. To thus obtained residue, water was added, pH was adjusted to 2 using concentrated hydrochloric acid and extraction was subjected using n-hexane. The obtained organic layer was dried over anhydrous magnesium sulfate, the insolubles were separated by filtration and then the solvent was distilled off under reduced pressure. Thus obtained residue was purified by silica gel column chromatography to obtain 0.5g of 5-sec-butyl-4-hydroxy-6-methyl-2-methylthiopyrimidine as a pale yellow powder (yield: 16%).
    [0471] Melting Point (°C) : 98 to 1001H-NMR Data (CDCl3/TMS δ (ppm)): 0.83 (t, 3H), 1.29 (d, 3H), 1.66 (m, 1H), 1.95 (m, 1H), 2.31 (s, 3H), 2.56 (s, 3H), 2.75 (m, 1H), 11.78 (br, 1H) <Reference Example 12>Production of 5-sec-butyl-4-chloro-6-methyl-2-methylthiopyrimidine
    [0472] Phosphorus oxychloride (6.5g, 42.4 mmol) and N,N-dimethylaniline (0.5g, 4.2 mmol) were added to 3.0g (14.1 mmol) of 5-sec-butyl-4-hydroxy-6-methyl-2-methylthiopyrimidine and the mixture was stirred for 2 hours at 100°C. After confirming the completion of reaction, the reaction solution was poured into water and extracted with dichloromethane. The obtained organic layer was washed with water and then washed with a saturated aqueous sodium bicarbonate solution and dried over anhydrous magnesium sulfate. The insolubles were separated by filtration and then the solvent was distilled off under reduced pressure. Thus obtained residue was purified by silica gel column chromatography to obtain 3.0g of 5-sec-butyl-4-chloro-6-methyl-2-methylthiopyrimidine as a yellow transparent oily substance (yield: 92%).
    [0473] Refractive Index (nD 20): 1.56131H-NMR Data (CDCl3/TMS δ (ppm)): 0.85 (t, 3H), 1.33 (d, 3H), 1.75 (m, 1H), 1.87 (m, 1H), 2.53 (s, 3H), 2.54 (s, 3H), 3.19 (br, 1H) <Reference Example 13>Production of 5-sec-butyl-4-chlorc-6-methyl-2-methylsulfonylpyrimidine
    [0474] 7.5g of m-chloroperbenzoic acid (purity: 70%, 30.3 mmol) was added to 200 ml of a dichloromethane solution containing 2.8g (12.1 mmol) of 5-sec-butyl-4-chloro-6-methyl-2-methylthiopyrimidine under ice cooling and the mixture was stirred for 30 minutes. Then, the mixture was further stirred for 2 hours at room temperature. After confirming the completion of reaction, the reaction solution was poured into water and extracted with dichloromethane. The obtained organic layer was washed with an aqueous solution of sodium bisulfite, water, an aqueous sodium bicarbonate solution and brine in this order and then dried over anhydrous magnesium sulfate. The insolubles were separated by filtration and then the solvent was distilled off under reduced pressure, to obtain 3.3g of 5-sec-butyl-4-chloro-6-methyl-2-methylsulfonylpyrimidine as a colorless transparent oily substance (yield: quantitative).
    [0475] Refractive Index (nD 20): 1.53681H-NMR Data (CDCl3/TMS δ (ppm)): 0.88 (t, 3H), 1.39 (d, 3H), 1.82 (m, 1H), 1.90 (m, 1H), 2.73 (s, 3H), 3.35 (s, 3H), 3.35 (br, 1H) <Reference Example 14>Production of 5-sec-butyl-4-chloro-6-methyl-2-(1H-pyrazol-1-yl)pyrimdine
    [0476] 0.9g (12.9 mmol) of pyrazole was added to 20 ml of a tetrahydrofuran solution containing 0.5g of sodium hydride (purity: 60%, 12.9 mmol) at 0°C and the mixture was stirred for 30 minutes at room temperature. To 20 ml of a tetrahydrofuran solution containing 3.1g (11.7 mmol) of 5-sec-butyl-4-chloro-6-methyl-2-methylsulfonylpyrimidine, a solution prepared in advance was added dropwise at -70°C and the mixture was stirred for 10 minutes at the same temperature. After confirming the completion of reaction, 100 ml of water was added to the reaction solution and the reaction solution was extracted with diethylether. The obtained organic layer was washed with water and dried over anhydrous magnesium sulfate. The insoluble were separated by filtration and then the solvent was distilled off under reduced pressure, to obtain 3.17g of 5-sec-butyl-4-chloro-6-methyl-2-(1H-pyrazol-1-yl)pyrimidine as a yellow transparent oily substance (yield: quantitative).
    [0477] Refractive Index (nD 20): 1.56111H-NMR Data (CDCl3/TMS δ (ppm)): 0.87 (t, 3H), 1.39 (d, 3H), 2.00-1.77 (m, 2H), 2.68 (s, 3H), 3.35 (br, 1H), 6.48 (s, 1H), 7.81 (s, 1H), 8.54 (d, 1H) <Reference Example 15>Production of 5-sec-butyl-6-chloro-2-hydrazinyl-N-(2,2,2-trifluoroethyl)pyrimidine-4-amine
    [0478] 0.2g (4.0 mmol) of hydrazine monohydrate was added to 40 ml of an ethanol solution containing 1.3g (3.6 mmol) of 5-sec-butyl-6-chloro-2-methylsulfonyl-N-(2,2,2-trifluoroethyl)pyrimidine-4-amine at room temperature and the mixture was stirred for 4 hours under reflux. After confirming the completion of reaction, the solvent was distilled off under reduced pressure. To the resultant, water was added and the mixture was extracted with chloroform. The obtained organic layer was washed with water and then dried over anhydrous magnesium sulfate. The insolubles were separated by filtration and then the solvent was distilled off under reduced pressure. Thus obtained residue was purified by silica gel column chromatography to obtain 1.1g of 5-sec-butyl-6-chloro-2-hydrazinyl-N-(2,2,2-trifluoroethyl)pyrimdine-4-gamine as a pale yellow oily substance (yield: 98%).
    [0479] Refractive Index (nD 20): 1.51361H-NMR Data (CDCl3/TMS δ (ppm)): 0.87 (t, 3H), 1.28 (d, 3H), 1.65-1.70 (m, 2H), 3.27 (br, 1H), 3.86 (br, 1H), 4.18-4.29 (m, 2H), 4.96 (br, 1H), 6.03 (br, 1H) <Reference Example 16>Production of 5-sec-butyl-4-chloro-6-iodo-2-methylthiopyrimidine
    [0480] 5.0g (19.9 mmol) of 5-sec-butyl-4,6-dichloro-2-methylthiopyrimidine was added to 30 ml of 55% hydroiodic acid and the mixture was stirred for 2 hours at room temperature. The reaction solution was poured into water, neutralized with a saturated sodium bicarbonate solution and extracted with diethylether. The obtained organic layer was washed with water and then dried over anhydrous magnesium sulfate. The insolubles were separated by filtration and then the solvent was distilled off under reduced pressure, to obtain 6.0g of crude 5-sec-butyl-4-chloro-6-iodo-2-methylthiopyrimidine (yield: 81%). <Reference Example 17>Production of 5-sec-butyl-4-chloro-2-methylthio-6-trifluoromethylpyrimidine
    [0481] 9.1g (64.0 mmol) of trifluoromethyltrimethylsilane, 1.5g (25.6 mmol) of potassium fluoride and 4.9g (25.6 mmol) of copper iodide were added to 50 ml of an N-methyl-2-pyrrolidinone solution containing 8.8g (25.6 mmol) of crude 5-sec-butyl-4-chloro-6-iodo--2-methylthiopyrimidine at room temperature and the mixture was stirred for 1 hour at 60°C. After confirming the completion of reaction, the reaction solution was poured into water and extracted with ethyl acetate. The obtained organic layer was washed with water and then dried over anhydrous magnesium sulfate. The insolubles were separated by filtration and then the solvent was distilled off under reduced pressure, to obtain 6.0g of crude 5-sec-butyl-4-chloro-2-methylthio-6-trifluoromethylpyrimidine (yield: 83%). <Reference Example 18>Production of 5-sec-butyl-4-chloro-2-methylsulfonyl-6-trifluoromethylpyrimidine
    [0482] 5.7g of m-chloroperbenzoic acid (purity: 70%, 23.4 mmol) was added to 30 ml of a dichloromethane solution containing 3.0g (10.6 mmol) of crude 5-sec-butyl-4-chloro-2-methylthio-6-trifluoromethylpyrimidine under ice cooling and the mixture was stirred for 30 minutes. Then, the mixture was further stirred for 1 hour at room temperature. After confirming the completion of reaction, the reaction solution was poured into water and extracted with dichloromethane. The obtained organic layer was washed with an aqueous solution of sodium bisulfite, water, an aqueous sodium bicarbonate solution, water and brine in this order and then dried over anhydrous magnesium sulfate. The insolubles were separated by filtration and then the solvent was distilled off under reduced pressure, to obtain 1.8g of crude 5-sec-butyl-4-chloro-2-methylsulfonyl-6-trifluoromethylpyrimidine (yield: 54%). <Reference Example 19>Production of 5-sec-butyl-4-chloro-2-(1H-pyrazol-1-yl)-6-trifluoromethylpyrimidine
    [0483] 0.41g (6.0 mmol) of 1H-pyrazole was added to 20 ml of a tetrahydrofuran solution containing 0.26g of sodium hydride (purity: 60%, 5.7 mmol) at room temperature and the mixture was stirred for 30 minutes. The reaction solution was cooled to -78°C, 1.8g (5.7 mmol) of crude 5-sec-butyl-4-chloro-2-methylsulfonyl-6-trifluoromethylpyrimidine was added thereto and the mixture was stirred for 10 minutes. After confirming the completion of reaction, the reaction solution was poured into water and extracted with ethyl acetate. The obtained organic layer was washed with water and then dried over anhydrous magnesium sulfate. The insolubles were separated by filtration and then the solvent was distilled off under reduced pressure, to obtain 0.90g of crude 5-sec-butyl-4-chloro-2-(1H-pyrazol-1-yl)-6-trifluoromethylpyrimidine (yield: 52%). <Reference Example 20>Production of 5-sec-butyl-4-chloro-6-ethyl-2-methylthiopyrimidine
    [0484] 0.2g (0.2 mmol) of [1,1-bis(diphenylphosphino)ferrocene]dichloropalladium complexed with dichloromethane was added to 50 ml of a tetrahydrofuran solution containing 3.0g (24.4 mmol) of 5-sec-butyl-4,6-dichloro-2-methylthiopyrimidine at room temperature and thereto 36.6 ml (1.00 mol/l, 36.6 mmol) of a tetrahydrofuran solution of ethyl magnesium bromide was further added dropwise at 45°C. The mixture was stirred for 2 hours at the same temperature. After confirming the completion of reaction, an aqueous solution of saturated ammonium chloride was added under ice cooling, the reaction mixture was heated to room temperature and extracted with ethyl acetate. The obtained organic layer was washed with water and then dried over anhydrous magnesium sulfate. The insolubles were separated by filtration and then the solvent was distilled off under reduced pressure. Thus obtained residue was purified by silica gel column chromatography to obtain 5.2g of 5-sec-butyl-4-chloro-6-ethyl-2-methylthiopyrimidine (yield: 87%).
    [0485] 1H-NMR Data (CDCl3/TMS δ (ppm)): 0.85 (t, 3H), 1.24-1.37 (m, 6H), 1.76-1.82 (m, 3H), 2.55 (s, 3H), 2.81 (q, 2H) <Reference Example 21>Production of 5-sec-butyl-6-ethyl-2-methylthio-N-(2,2,2-trifluoroethyl)pyrimidine-4-amine
    [0486] 2.1g (21.7 mmol) of 2,2,2-trifluoroethylamine and a catalytic amount of sodium p-toluenesulfinate were added to 20 ml of a 1,3-dimethyl-2-imidazolidinone solution containing 1.8g (7.2 mmol) of 5-sec-butyl-4-chloro-6-ethyl-2-methylthiopyrimidine. In a sealed tube, the mixture was stirred for 56 hours at 150°C. After confirming the completion of reaction, the reaction solution was poured into water and extracted with ethyl acetate. The obtained organic layer was washed with water and then dried over anhydrous magnesium sulfate. The insolables were separated by filtration and then the solvent was distilled off under reduced pressure. Thus obtained residue was purified by silica gel column chromatography to obtain 1.7g of 5-sec-butyl-6-ethyl-2-methylthio-N-(2,2,2-trifluoroethyl)pyrimidine-4-amine (yield: 75%).
    [0487] 1H-NMR Data (CDCl3/TMS δ (ppm)): 0.88 (t, 3H), 1.19-1.31 (m, 6H), 1.59-1.75 (m, 2H), 2.61-2.74 (m, 1H), 3.01 (br, 1H), 4.23-4.34 (m, 2H), 4.80 (br, 1H) <Reference Example 22>Production of 5-sec-butyl-6-ethyl-2-methylsulfonyl-N-(2,2,2-trifluoroethyl)pyrimidine-4-amine
    [0488] 3.3g of m-chloroperbenzoic acid (purity: 70%, 13.5 mmol) was added to 100 ml of a dichloromethane solution containing 1.7g (5.4 mmol) of 5-sec-butyl-6-ethyl-2-methylthio-N-(2,2,2-trifluoroethyl)pyrimidine-4-amine under ice cooling and the mixture was stirred for 30 minutes. Then, the mixture was further stirred at room temperature for 24 hours. After confirming the completion of reaction, the reaction solution was poured into water and extracted with dichloromethane. The obtained organic layer was washed with an aqueous solution of sodium bisulfite, water, an aqueous sodium bicarbonate solution and brine in this order and the dried over anhydrous magnesium sulfate. The insolubles were separated by filtration and then the solvent was distilled off under reduced pressure. Thus obtained residue was purified by silica gel column chromatography to obtain 1.12g of 5-sec-butyl-6-ethyl-2-methylsulfonyl-N-(2,2,2-trifluoroethyl)pyrimidine-4-amine (yield: 61%).
    [0489] 1H-NMR Data (CDCl3/TMS δ (ppm)): 0.91 (t, 3H), 1.24-1.36 (m, 6H), 1.65-1.79 (m, 2H), 2.78-2.86 (m, 2H), 3.02 (br, 1H), 3.29 (s, 3H), 4.27-4.38 (m, 2H), 5.18 (br, 1H) <Reference Example 23>Production of 5-sec-butyl-4,6-dibromo-2-methylthiopyrimidine
    [0490] 13.4g (46.7 mmol) of phosphorus oxybromide was added to 40 ml of a chlorobenzene solution containing 5.0g (23.3 mmol) of 5-sec-butyl-2-methylthiopyrimidine-4,6-diol and the mixture was stirred for 3 hours under reflux. After confirming the completion of reaction, the reaction solution was poured into water and extracted with dichloromethane. The obtained organic layer was washed with water and then washed with a saturated aqueous sodium bicarbonate solution and then dried over anhydrous magnesium sulfate. The insolubles were separated by filtration and then the solvent was distilled off under reduced pressure. Thus obtained residue was purified by silica gel column chromatography to obtain 2.1g of 5-sec-butyl-4,6-dibromo-2-methylthiopyrimidine (yield: 26%).
    [0491] 1H-NMR Data (CDCl3/TMS δ (ppm)): 0.86 (t, 3H), 1.37 (d, 3H), 1.70-1.81 (m, 1H), 2.00-2.10 (m, 1H), 2.55 (s, 3H), 3.46-3.51 (m, 1H) <Reference Example 24>Production of 6-bromo-5-sec-butyl-2-methylthio-N-(2,2,2-trifuoroethyl)pyrimidine-4-amine
    [0492] 1.8g (18.5 mmol) of 2,2,2-trifluoroethylamine was added to 10 ml of a 1,3-dimethyl-2-imidazolidinone solution containing 2.1g (6.2 mmol) of 5-sec-butyl-4,6-dibromo-2-methylthiopyrimidine. In a sealed tube, the mixture was stirred for 10 hours at 120°C. After confirming the completion of reaction, the reaction solution was poured into water and extracted with ethyl acetate. The obtained organic layer was washed with water and then dried over anhydrous magnesium sulfate. The insolubles were separated by filtration and then the solvent was distilled off under reduced pressure. Thus obtained residue was purified by silica gel column chromatography to obtain 2.2g of 6-bromo-5-sec-butyl-2-methylthio-N-(2,2,2-trifluoroethyl)pyrimidine-4-amine (yield: 99%).
    [0493] 1H-NMR Data (CDCl3/TMS δ (ppm)): 0.91 (t, 3H), 1.28 (d, 3H), 1.66-1.71 (m, 2H), 2.49 (s, 3H), 3.40 (br, 1H), 4.21-4.32 (m, 2H), 4.99 (br, 1H) <Reference Example 25>Production of 6-bromo-5-sec-butyl-2-methylsulfonyl-N-(2,2,2-trifluoroethyl)pyrimidine-4-amine
    [0494] 3.8g of m-chloroperbenzoic acid (purity: 70%, 15.2 mmol) was added to 60 ml of a dichloromethane solution containing 2.2g (6.1 mmol) of 6-bromo-5-sec-butyl-2-methylthio-N-(2,2,2-trifluoroethyl)pyrimidine-4-amine under ice cooling and the mixture was stirred for 30 minutes. Then the mixture was further stirred at room temperature for 2 hours. After confirming the completion of reaction, the reaction solution was poured into water and extracted with dichloromethane. The obtained organic layer was washed with an aqueous solution of sodium bisulfite, water, an aqueous sodium bicarbonate solution and brine in this order and then dried over anhydrous magnesium sulfate. The insolubles were separated by filtration and then the solvent was distilled off under reduced pressure, to obtain 2.32g of 6-bromo-5-sec-butyl-2-methylsulfonyl-N-(2,2,2-trifluorcethyl)pyrimidine-4-aimine (yield: 98%).
    [0495] 1H-NMR Data (CDCl3/TMS δ (ppm)): 0.94 (t, 3H), 1.33 (d, 3H), 1.73-1.78 (m, 2H), 3.29 (s, 3H), 3.52 (br, 1H), 4.28-4.39 (m, 2H), 5.39 (br, 1H) <Reference Example 26>Production of 5-sec-butyl-N4,N4-diethyl-2-methylthio-N6-(2,2,2-trifluoroethyl)pyrimidine-4,6-diamine
    [0496] 1.1g (15.0 mmol) of diethylamine and a catalytic amount of sodium p-toluenesulfinate were added to 10 ml of a 1,3-dimethyl-2-imidazolidinone solution containing 1.0g (3.0 mmol) of 5-sec-butyl-6-chloro-2-methylthio-N-(2,2,2-trifluoroethyl)pyrimidine-4-amine. In a sealed tube, the mixture was stirred for 23 hours at 150°C. After confirming the completion of reaction, the reaction solution was poured into water and extracted with ethyl acetate. The obtained organic layer was washed with water and then dried over anhydrous magnesium sulfate. The insolubles were separated by filtration and then the solvent was distilled off under reduced pressure. Thus obtained residue was purified by silica gel column chromatography to obtain 1.1g of 5-sec-butyl-N4,N4-diethyl-2-methylthio-N6-(2,2,2-trifluoroethyl)pyrimidine-4,6-diamine (yield: quantitative). <Reference Example 27>Production of 5-sec-butyl-N4,N4-diethyl-2-methylsulfonyl-N6-(2,2,2-trifluoroethyl)pyrimidine-4,6-diamine
    [0497] 1.9g of m-chloroperbenzoic acid (purity: 70%, 7.5 mmol) was added, under ice cooling, to 50 ml of a chloroform solution containing 1.1g(3.0 mmol) of 5-sec-butyl-N4,N4-diethyl-2-methylthio-N6-(2,2,2-trifluoroethyl)pyrimidine-4,6-diamine obtained in Reference Example 26 and the mixture was stirred for 30 minutes. Then, the mixture was further stirred overnight at room temperature. After confirming the completion of reaction, the reaction solution was poured into water and extracted with chloroform. The organic layer was washed with an aqueous solution of sodium bisulfite, water, an aqueous sodium bicarbonate solution and brine in this order and then dried over anhydrous magnesium sulfate. The insolubles were separated by filtration and then the solvent was distilled off under reduced pressure. Thus obtained residue was purified by silica gel column chromatography to obtain 0.6g of 5-sec-butyl-N4,N4-diethyl-2-methylsulfonyl-N6-(2,2,2-trifluoroethyl)pyrimidine-4,6-diamine (yield: 52%).
    [0498] 1H-NMR Data (CDCl3/TMS δ (ppm)): 0.83 (t, 3H), 1.15 (t, 6H), 1.30 (d,2H), 1.66 (m, 2H), 3.02 (q, 1H), 3.17 (m, 2H), 3.24 (s, 3H), 3.34 (m, 2H), 4.30 (m, 2H), 4.91 (br, 1H)
    [0499] Next, a formulation preparing method will be described in detail with reference to representative Formulation Examples. The type and blending ratio of the compound and additive are not limited thereto and they can be changed in a wide range. In the description below, 'parts' means 'parts by weight'. [Formulation Example 1] Wettable Powder
    [0500] 0.5 parts of polyoxyethyleneoctylphenyl ether, 0.5 parts of a sodium salt of β-naphthalene sulfonic acid formalin condensate, 20 parts of diatomite and 69 parts of clay were mixed with 10 parts of Compound No. 0259 and the mixture was crushed to obtain wettable powder. [Formulation Example 2] Wettable Powder
    [0501] 50 parts of the compound of Compound No. 0350, 45 parts of diatomite, 2 parts of sodium dinaphthylmethanedisulfonate and 3 parts of sodium lignin sulfonate were homogeneously mixed and crushed to obtain wettable powder. [Formulation Example 3] Flowable
    [0502] 0.2 parts of xanthan gum was dissolved in 75.8 parts of water. Thereto, in addition to 13 parts of the compound of Compound No. 0147, 4 parts of polyoxyethylene styrenated phenyl ether sulfate and 7 parts of ethylene glycol, silicone AF-128N (produced by Asahi Chemical Industry Co., Ltd.) was also added by 130 ppm with respect to the total amount and they were mixed for 30 minutes with a high-speed stirrer. Thereafter, the mixture was crushed using a wet pulverizer to obtain a flowable. [Formulation Example 4] Emulsion
    [0503] 60 parts of a mixture of equal parts of xylene and isophorone and 10 parts of a surfactant obtained as a mixture of polyoxyethylene sorbitan alkylate, a polyoxyethylene alkylaryl polymer and alkylaryl sulfonate, were added to 30 parts of the compound of Compound No. 0919 and these were well stirred to obtain an emulsion. [Formulation Example 5] Granule
    [0504] To 5 parts of the compound of Compound No. 1215, 85 parts of a filler obtained by mixing talc and bentonite in a 1:3 ratio, 5 parts of white carbon and 5 parts of a surfactant obtained as a mixture of polyoxyethylene sorbitan alkylate, a polyoxyethylene alkylaryl polymer and alkylaryl sulfonate, there added 10 parts of water and the mixture was well kneaded to give a paste form. This paste product was pushed out through a sieve having a diameter of 0.7 mm, it was then dried and cut in a length of 0.5 to 1 mm, to obtain a Granule.
    [0505] With compounds shown in Tables 1 to 40, various formulations can be produced in the same manner according to Formulation Examples 1 to 5.
    [0506] Next, effects exhibited by the compound of the invention will be described with reference to Test Examples. [Test Example 1] Test on protective effect against Pyricularia oryzae
    [0507] 18 rice seeds (variety: Aichi Asahi) were sown in each clay pot having a diameter of 7.5 cm and allowed to grow for 2 to 4 weeks in a greenhouse. The wettable powder prepared according to Formulation Example 1 was diluted in water in the manner for an active ingredient concentration to be 500 ppm, a spreader (Kumiten) was added for the dilution factor to be 3,000 times and the resultant agent was sprayed to rice plants at a four-leaf stage in the amount of 20 ml per 1 pot. After air drying, the rice plants were inoculated by spraying a conidia suspension of Pyricularia oryzae and incubated in a moist chamber at 25°C (relative humidity of 100%) until a development of disease. 5 days after the innoculation, the number of lesion on a leaf that had been on the top at the time of spraying the agent was counted and a control level (%) was calculated using the expression shown below.
    [0508] According to this test, compounds providing a 100% control level were Compound Nos.: 0009, 0010, 0018, 0022, 0025, 0026, 0029, 0035, 0049, 0133, 0135, 0147, 0159, 0162, 0163, 0166, 0175, 0178, 0179, 0186, 0194, 0195, 0198, 0199, 0200, 0222, 0240, 0242, 0246, 0249, 0250, 0254, 0259, 0301, 0305, 0309, 0312, 0313, 0317, 0328, 0329, 0336, 0337, 0341, 0349, 0350, 0351, 0354, 0358, 0361, 0370, 0372, 0384, 0385, 0387, 0389, 0391, 0392, 0434, 0435, 0436, 0710, 0732, 0760, 0764, 0768, 0776, 0780, 0792, 0800, 0828, 0844, 0860, 0864, 0868, 0907, 0916, 0919, 0921, 0943, 0962, 0963, 0966, 0967, 0971, 0975, 0979, 0986, 0987, 0990, 0991, 0994, 0995, 0998, 1000, 1008, 1031, 1058, 1060, 1061, 1062, 1065, 1068, 1071, 1082, 1085, 1086, 1087, 1090, 1093, 1094, 1106, 1110, 1115, 1156, 1160, 1179, 1187, 1191, 1196, 1239, 1283, 1286, 1287, 1291, 1311, 1315, 1318, 1319, 1323, 1328, 1342, 1426, 1428, 1442, 1452, 1455, 1456, 1459, 1460, 1497, 1511, 1554, 1576, 1595, 1597, 1617, 1624, 1625, 1628, 1633, 1640, 1641, 1657, 1898 and the like.Herein, Comparative Compound 1 did not exhibit a control effect.
    [0509] Hereinbelow, an expression to calculate a control level (%) is shown. Control Level% = 1 - average lesion number on treated area average lesion number on untreated area × 100
    [0510] Comparative Compound 1 mentioned above is Compound No. 1-1693 disclosed in JP-A No. 2005-232081 . A structure thereof is shown below.
    [0511]
    [0512] 15 rice seeds (variety: Kinmaze) were sown in each clay pot having a diameter of 7.5 cm and allowed to grow for 3 weeks in a greenhouse. The wettable powder prepared according to Formulation Example 1 was diluted in water in the manner for an active ingredient concentration to be 500 ppm, a spreader (Kumiten) was added for the dilution factor to be 3,000 times and the resultant agent was sprayed to rice at a two and a half to three-leaf stage in the amount of 20 ml per 1 pot. After air drying, the plants were inoculated by uniformly covering the surface of the soil with Rhizoctonia solani cultured in a rice-husk bran medium and incubated in a moist chamber at 30°C (relative humidity of 100%) until a development of disease. 5 days after the innoculation, disease development indexes of total pots were examined according to the standard described below and a control level (%) was calculated using the expression shown below.
    [0513] According to this test, compounds providing a 100% control level were Compound Nos.: 0006, 0010, 0018, 0035, 0049, 0135, 0159, 0163, 0186, 0190, 0191, 0194, 0195, 0199, 0200, 0222, 0232, 0241, 0242, 0246, 0249, 0250, 0254, 0259, 0301, 0305, 0309, 0312, 0313, 0328, 0329, 0333, 0336, 0337, 0341, 0348, 0349, 0350, 0351, 0354, 0361, 0367, 0368, 0370, 0372, 0373, 0377, 0382, 0384, 0387, 0389, 0391, 0393, 0395, 0401, 0434, 0435, 0436, 0437, 0536, 0708, 0710, 0732, 0760, 0764, 0768, 0772, 0775, 0776, 0780, 0788, 0792, 0796, 0800, 0812, 0824, 0828, 0840, 0844, 0860, 0864, 0868, 0904, 0908, 0933, 0915, 0916, 0920, 0921, 0943, 0953, 0962, 0963, 0967, 0971, 0975, 0979, 0998, 1000, 1008, 1031, 1058, 1060, 1062, 1065, 1068, 1071, 1082, 1085, 1087, 1090, 1094, 1098, 1102, 1106, 1110, 1115, 1156, 1167, 1179, 1187, 1190, 1191, 1192, 1204, 1215, 1255, 1263, 1283, 1290, 1315, 1318, 1319, 1328, 1342, 1426, 1428, 1442, 1452, 1497, 1511, 1533, 1554, 1576, 1595, 1597, 1617, 1625, 1633, 1637, 1640, 1641, 1833, 1849, 1898, 1906, 1914, 1994, 2011 and the like. Herein, Comparative Compound 1 did not exhibit a control effect and Comparative Compound 2 showed a control level of 50%.
    [0514] The standard for disease development index is as follows: [Table 51] Disease Development index 0: Disease Development is not recognized 1: Infected height is less than 25% of that in untreated area 2: Infected height is 25% or more to less than 50% of that in untreated area 3: Infected height is 50% or more to less than 75% of that in untreated area 4: Infected height is 75% or more of that in untreated area
    [0515] Hereinbelow, an expression to calculate a control level (%) is shown. Control Level% = 1 - average disease development index of treated area average disease development index on untreated area × 100
    [0516] Herein, Comparative Compounds 1 and 2 mentioned above are Compound No. 1-1693 disclosed in JP-A No. 2005-232081 and Compound No. 182 disclosed in JP-A No. S54-115384 , respectively. A structure of Comparative Compound 1 is shown as above and a structure of Comparative Compound 2 is shown below.
    [0517]
    [0518] 4 cucumber seeds (variety: Sagami-Hanziro) were sown in each plastic cup having a diameter of 5.5 cm and allowed to grow for 7 days in a greenhouse. The wettable powder prepared according to Formulation Example 1 was diluted in water in the manner for an active ingredient concentration to be 500 ppm, a spreader (Kumiten) was added for the dilution factor to be 3,000 times and the resultant agent was sprayed to cucumber seedling the seed leaf of which is opened in the amount of 20 ml per 1 cup. After air drying, the plants were inoculated by spraying with a conidia suspension of Pseudoperonospora cubensis. The inoculated plants were immediately put in a moist chamber at 20°C (relative humidity of 100%) for 24 hours. Thereafter, the plants were transferred to a greenhouse. 6 days after, disease development indexes of cotyledons for total pots were examined according to the standard described below, a disease severity was determined using an expression shown below and a control level (%) was calculated using another expression shown below.
    [0519] According to this test, compounds providing a 100% control level were Compound Nos.: 0002, 0006, 0009, 0010, 0013, 0014, 0018, 0022, 0025, 0026, 0029, 0035, 0049, 0133, 0135, 0147, 0155, 0159, 0162, 0163, 0166, 0178, 0179, 0182, 0186, 0187, 0190, 0191, 0194, 0195, 0200, 0222, 0232, 0241, 0242, 0246, 0249, 0250, 0259, 0300, 0301, 0304, 0305, 0308, 0309, 0313, 0316, 0325, 0328, 0329, 0336, 0341, 0348, 0349, 0350, 0351, 0358, 0361, 0368, 0370, 0371, 0372, 0384, 0385, 0387, 0389, 0393, 0394, 0401, 0435, 0436, 0437, 0708, 0710, 0721, 0732, 0760, 0764, 0768, 0772, 0775, 0776, 0791, 0799, 0812, 0824, 0827, 0828, 0860, 0864, 0907, 0908, 0915, 0921, 0943, 0953, 0962, 0963, 0966, 0967, 0970, 0971, 0974, 0975, 0986, 0987, 0990, 0994, 1000, 1008, 1058, 1071, 1075, 1081, 1082, 1085, 1086, 1087, 1090, 1094, 1097, 1098, 1101, 1110, 1115, 1178, 1182, 1183, 1186, 1187, 1190, 1197, 1215, 1225, 1263, 1279, 1286, 1287, 1290, 1291, 1318, 1342, 1426, 1440, 1452, 1455, 1456, 1459, 1511, 1533, 1554, 1576, 1595, 1624, 1628, 1637, 1641, 1657, 1829, 1906 and the like. Comparative Compound 1 did not exhibit a control effect.
    [0520] The standard for disease development index is as follows: [Table 52] Disease Development Index 0: Disease Development is not recognized 1: disease development area of less than 25% 2: disease development area of 25% or more to less than 50% 3: disease development area of 50% or more to less than 75% 4: disease development area of 75% or more
    [0521] Hereinbelow, an expression to calculate a disease severity (%) is shown. disease severity =n ⁢ 0 × 0 + n ⁢ 1 × 1 + n ⁢ 2 × 2 + n ⁢ 3 × 3 + n ⁢ 4 × 4 4 × N× 100
    [0522] provided that, N: total number of examined leaves n0: number of leaves of disease development index 0 n1: number of leaves of disease development index 1 n2: number of leaves of disease development index 2 n3: number of leaves of disease development index 3 n4: number of leaves of disease development index 4
    [0523] Hereinbelow, an expression to calculate a control level (%) is shown. control level% = 1 - disease severity of treated area disease severity of untreated area × 100
    [0524] Comparative Compound 1 mentioned above is Compound No. 1-1693 disclosed in JP-A No. 2005-232081 mentioned before. <Test Example 4> Test on protective effect against Botrytis cinerea
    [0525] 4 cucumber seeds (variety: Sagami-Hanziro) were sown in each plastic cup having a diameter of 5.5 cm and allowed to grow for 7 days in a greenhouse. The wettable powder prepared according to Formulation Example 1 was diluted in water in the manner for an active ingredient concentration to be 500 ppm, a spreader (Kumiten) was added for the dilution factor to be 3,000 times and the resultant agent was sprayed to cucumber seedling the seed leaf of which is opened in the amount of 20 ml per 1 cup. After air drying, a sterilized paper disc was immersed in a conidia suspension of Botrytis cinerea and laid on an upper side of a cucumber cotyledon for innoculation and thereafter cared in a moist chamber at 20°C (relative humidity of 100%) until a development of disease. 2 days after, disease development indexes of total pots were examined according to the standard in Test Example 3, a disease severity was determined using the expression in Test Example 3 and a control level (%) was calculated using the expression in Test Example 3.
    [0526] According to this test, compounds providing a 100% control level were Compound Nos.: 0049, 0195, 0200, 0222, 0242, 0250, 0254, 0259, 0309, 0313, 0349, 0350, 0351, 0372, 0401, 0434, 0435, 0436, 0437, 0710, 0732, 0776, 0860, 0864, 0943, 1000, 1008, 1086, 1087, 1090, 1097, 1115, 1328, 1342, 1554, 1576, 1845 and the like. Comparative Compound 1 did not exhibit a control effect and Comparative Compound 2 showed a control level of 25%.
    [0527] Herein, Comparative Compounds 1 and 2 mentioned above are Compound No. 1-1693 disclosed in JP-A No. 2005-232081 and Compound No. 182 disclosed in JP-A No. S54-115384 , respectively. <Test Example 5> Test on protective effect against Erysiphe graminis
    [0528] 10 wheat seeds (variety: Norin No. 61) were sown in each plastic cup having a diameter of 5.5 cm and allowed to grow for 8 days in a greenhouse. The wettable powder prepared according to Formulation Example 1 was diluted in water in the manner for an active ingredient concentration to be 500 ppm, a spreader (Kumiten) was added for the dilution factor to be 3,000 times and the resultant agent was sprayed to wheat at a one and a half to two-leaf stage in the amount of 20 ml per 1 cup. After air drying, the plants were inoculated by equally sprinkling with conidia of Erysiphe graminis by using a midget duster or the like for innoculation and then incubated in a greenhouse until a development of disease. 7 days after, disease development indexes of first leaves for total pots were examined according to the standard in Test Example 3, a disease severity was determined using the expression in Test Example 3 and a control level (%) was calculated using the expression in Test Example 3.
    [0529] According to this test, compounds providing a 100% control level were Compound Nos.: 0010, 0018, 0022, 0025, 0026, 0029, 0035, 0133, 0135, 0149, 0162, 0163, 0166, 0167, 0178, 0179, 0183, 0186, 0187, 0194, 0199, 0200, 0211, 0222, 0232, 0240, 0249, 0259, 0305, 0309, 0312, 0313, 0317, 0333, 0341, 0349, 0350, 0351, 0354, 0355, 0358, 0361, 0370, 0371, 0373, 0384, 0385, 0386, 0387, 0389, 0391, 0392, 0401, 0434, 0437, 0708, 0710, 0721, 0732, 0760, 0764, 0768, 0792, 0796, 0800, 0844, 0864, 0900, 0901, 0902, 0906, 0907, 0915, 0916, 0919, 0920, 0921, 0934, 0943, 0953, 0961, 0962, 0963, 0966, 0967, 0970, 0971, 0975, 0979, 0986, 0987, 0990, 0991, 0994, 0995, 0998, 1000, 1008, 1030, 1058, 1060, 1061, 1062, 1064, 1065, 1087, 1089, 1093, 1094, 1097, 1098, 1101, 1102, 1115, 1156, 1160, 1178, 1179, 1182, 1183, 1186, 1187, 1190, 1191, 1192, 1196, 1197, 1204, 1215, 1225, 1233, 1239, 1243, 1254, 1255, 1259, 1286, 1287, 1290, 1291, 1311, 1318, 1322, 1328, 1342, 1426, 1428, 1440, 1442, 1448, 1452, 1455, 1456, 1497, 1511, 1554, 1576, 1595, 1597, 1624, 1625, 1633, 1640, 1641, 1645, 1657, 1661, 1898, 1906, 1914 and the like. <Test Example 6> Test on protective effect against Septoria nodorum
    [0530] 10 wheat seeds (variety: Norin No. 61) were sown in each plastic cup having a diameter of 5.5 cm and allowed to grow for 9 days in a greenhouse. The wettable powder prepared according to Formulation Example 1 was diluted in water in the manner for an active ingredient concentration to be 500 ppm, a spreader (Kumiten) was added for the dilution factor to be 3,000 times and the resultant agent was sprayed to wheat at a two-leaf stage in the amount of 20 ml per 1 cup. After air drying, the plants were inoculated by spraying with a pycnidiospore suspension of Septoria nodorum. The inoculated plants were immediately put in a moist chamber at 25°C (relative humidity of 100%) for 48 hours. Thereafter, the plants were transferred to a greenhouse. 9 days after, disease development indexes of first leaves for total pots were examined according to the standard in Test Example 3, a disease severity was determined using the expression in Test Example 3 and a control level (%) was calculated using the expression in Test Example 3.
    [0531] According to this test, compounds providing a 100% control level were Compound Nos.: 0002, 0006, 0009, 0010, 0014, 0018, 0025, 0029, 0049, 0133, 0147, 0162, 0163, 0166, 0167, 0178, 0179, 0182, 0186, 0187, 0191, 0194, 0198, 0232, 0241, 0242, 0245, 0249, 0253, 0259, 0300, 0312, 0313, 0316, 0328, 0329, 0332, 0341, 0349, 0350, 0351, 0367, 0384, 0385, 0401, 0710, 0732, 0764, 0772, 0775, 0776, 0791, 0799, 0812, 0860, 0868, 0907, 0908, 0915, 0916, 0919, 0921, 0953, 0962, 0963, 0966, 0967, 0970, 0979, 0990, 0994, 1000, 1008, 1062, 1065, 1087, 1085, 1087, 1093, 1115, 1178, 1182, 1183, 1186, 1187, 1190, 1225, 1263, 1286, 1290, 1318, 1322, 1342, 1426, 1452, 1459, 1511, 1533, 1595, 1640, 1641, 1644, 1898, 1906, 1918, 1794 and the like. Comparative Compound 1 did not exhibit a control effect and Comparative Compound 2 showed a control level of 75%.
    [0532] Herein, Comparative Compounds 1 and 2 mentioned above are Compound No. 1-1693 disclosed in JP-A No. 2005-232081 and Compound No. 182 disclosed in JP-A No. S54-115384 , respectively.
    权利要求:
    Claims (8)
    [0001] A plant disease control agent for agricultural or horticultural use, which is characterized by containing as an active ingredient one or more compounds selected from aminopyrimidine derivatives represented by General Formula [I]:
    [0002] An aminopyrimidine derivative represented by General Formula [I]:
    [0003] The aminopyrimidine derivative or an agriculturally acceptable salt thereof according to Claim 2,wherein, in General Formula [I],R1 is a hydrogen atom, a C1-10 alkyl group which may be substituted with one or more substituents selected from Substituent Group α, a C1-10 alkoxy group which may be substituted with one or more substituents selected from Substituent Group α, a C3-8 cycloalkyl group, a C2-6 alkynyl group, a C2-6 alkenyl group, a C1-6 acyl group, a hydroxyl group, a C1-6 haloalkylcarbonyl group, a C1-6 alkoxycarbonyl group, a carbamoyl group, a mono(C1-6 alkyl)aminocarbonyl group, a di(C1-6 alkyl) aminocarbonyl group, a C1-6 alkylsulfonyl group, a C1-6 haloalkylsulfonyl group, a sulfamoyl group, a mono(C1-6 alkyly)aminosulfonyl group or a di(C1-6 alkyl) aminosulfonyl group andR2 is a C1-10 alkyl group which may be substituted with one or more substituents selected from Substituent Group α, a C1-10 alkoxy group which may be substituted with one or more substituents selected from Substituent Group α, a C3-8 cycloalkyl group, a C2-6 alkynyl group, a C2-6 alkenyl group, a C1-6 acyl group, a C1-6 haloalkylcarbonyl group, a C1-6 alkoxycarbonyl group, a carbamoyl group, a mono(C1-6 alkyl)aminocarbonyl group, a di(C1-6 alkyl)aminocarbonyl group, a C1-6 alkylsulfonyl group, a C1-6 haloalkylsulfonyl group, a sulfamoyl group, a mono(C1-6 alkyl)aminosulfonyl group or a di(C1-6 alkyl)aminosulfonyl group,while R1 and R2 may form a 5-membered or 6-membered ring (the 5-membered or 6-membered ring may be substituted with one or more substituents selected from Substituent Group α) with an atom arbitrarily selected from the group consisting of a carbon atom, an oxygen atom, a nitrogen atom and a sulfur atom, together with the nitrogen atom to which R1 and R2 are bonded.
    [0004] The aminopyrimidine derivative or an agriculturally acceptable salt thereof according to Claim 2,wherein, in General Formula [I],R1 is a C1-10 alkyl group which may be substituted with one or more substituents selected from Substituent Group β, a C1-10 alkoxy group which may be substituted with one or more substituents selected from Substituent Group α, a C3-8 cycloalkyl group, a C2-6 alkynyl group, a C2-6 alkenyl group, a C1-6 acyl group, a hydroxyl group, a C1-6 haloalkylcarbonyl group, a C1-6 alkoxycarbonyl group, a carbamoyl group, a mono(C1-6 alkyl)aminocarbonyl group, a di(C1-6 alkyl)aminocarbonyl group, a C1-6 alkylsulfonyl group, a C1-6 haloalkylsulfonyl group, a sulfamoyl group, a mono(C1-6 alkyl)aminosulfonyl group or a di(C1-6 alkyl)aminosulfonyl group andR2 is a hydrogen atom, a C1-10 alkyl group which may be substituted with one or more substituents selected from Substituent Group α, a C1-10 alkoxy group which may be substituted with one or more substituents selected from Substituent Group α, a C3-8 cycloalkyl group, a C2-6 alkynyl group, a C2-6 alkenyl group, a C1-6 acyl group, a C1-6 haloalkylcarbonyl group, a C1-6 alkoxycarbonyl group, a carbamoyl group, a mono(C1-6 alkyl) aminocarbonyl group, a di(C1-6 alkyl)aminocarbonyl group, a C1-6 alkylsulfonyl group, a C1-6 haloalkylsulfonyl group, a sulfamoyl group, a mono(C1-6 alkyl)aminosulfonyl group or a di(C1-6 alkyl)aminosulfonyl group,while R1 and R2 may form a 5-membered or 6-membered ring (the 5-membered or 6-membered ring is independently substituted with 1 to 4 halogen atoms or/and a C1-6 haloalkyl group) with an atom arbitrarily selected from the group consisting of a carbon atom, an oxygen atom, a nitrogen atom and a sulfur atom, together with the nitrogen atom to which R1 and R2 are bonded,where Substituent Group β being defined as follows:
    "Substituent Group β":
    a halogen atom, a C2-6 alkynyl group, a C3-8 cycloalkyloxy group, a C3-8 cycloalkyl C1-3 alkyloxy group, a C1-6 haloalkoxy group, a C2-6 alkenyloxy group, a C2-6 alkenyloxy group, a C1-6 haloalkyl group, a C1-6 alkylthio group, a C1-6 alkylsulfinyl group, a C1-6 alkylsulfonyl group, a C1-6 haloalkylthio group, a C1-6 haloalkylsulfinyl group, a C1-6 haloalkylsulfonyl group, a cyano group, a nitro group, a C1-6 acyl group, a carboxyl group, a C1-6 alkoxycarbonyl group, a carbamoyl group, a mono(C1-6 alkyl) aminocarbonyl group, a di(C1-6 alkyl)aminocarbonyl group and a tri(C1-6 alkyl)silyl group.
    [0005] The aminopyrimidine derivative or an agriculturally acceptable salt thereof according to Claim 2,wherein, in General Formula [I],R1 is a hydrogen atom, a C1-10 alkyl group which may be substituted with one or more substituents selected from Substituent Group α, a C1-10 alkoxy group which may be substituted with one or more substituents selected from Substituent Group α, a C3-8 cycloalkyl group, a C2-6 alkynyl group, a C2-6 alkenyl group, a C1-6 acyl group, a hydroxyl group, a C1-6 haloalkylcarbonyl group, a C2-6 alkoxycarbonyl group, a carbamoyl group, a mono(C1-6 alkyl)aminocarbonyl group, a di(C1-6 alkyl)aminocarbonyl group, a C1-6 alkylsulfonyl group, a C1-6 haloalkylsulfonyl group, a sulfamoyl group, a mono(C1-6 alkyl)aminosulfonyl group or a di(C1-6 alkyl)aminosulfonyl group andR2 is a hydrogen atom, a C1-10 alkyl group which may be substituted with one or more substituents selected from Substituent Group β, a C1-10 alkoxy group which may be substituted with one or more substituents selected from Substituent Group α, a C2-6 alkynyl group, a C1-6 acyl group, a C1-6 haloalkylcarbonyl group, a C1-6 alkoxycarbonyl group, a carbamoyl group, a mono(C1-6 alkyl) aminocarbonyl group, a di(C1-6 alkyl)aminocarbonyl group, a C1-6 alkylsulfonyl group, a C1-6 haloalkylsulfonyl group, a sulfamoyl group, a mono(C1-6 alkyl)aminosulfonyl group or a di(C1-6 alkyl)aminosulfonyl group,while R1 and R2 may form a 5-membered or 6-membered ring (the 5-membered or 6-membered ring is independently substituted with 1 to 4 halogen atoms or/and a C1-6 haloalkyl group) with an atom arbitrarily selected from the group consisting of a carbon atom, an oxygen atom, a nitrogen atom and a sulfur atom, together with the nitrogen atom to which R1 and R2 are bonded,where Substituent Group P being defined as follows:
    "Substituent Group β:
    a halogen atom, a C2-6 alkynyl group, a C3-8 cycloalkyloxy group, a C3-8 cycloalkyl C1-3 alkyloxy group, a C1-6 haloalkoxy group, a C2-6 alkynyloxy group, a C2-6 alkenyloxy group, a C1-6 haloalkyl group, a C1-6 alkylthio group, a C1-6 alkylsulfinyl group, a C1-6 alkylsulfonyl group, a C1-6 haloalkylthio group, a C1-6 haloalkylsulfinyl group, a C1-6 haloalkylsulfonyl group, a cyano group, a nitro group, a C1-6 acyl group, a carboxyl group, a C1-6 alkoxycarbonyl group, a carbamoyl group, a mono(C1-6 alkyl)aminocarbonyl group, a di(C1-6 alkyl)aminocarbonyl group and a tri(C1-6 alkyl)silyl group.
    [0006] The aminopyrimidine derivative or an agriculturally acceptable salt thereof according to Claim 5,wherein, in General Formula [I],R2 is a C1-10 alkyl group which may be substituted with one or more substituents selected from Substituent Group β, a C1-10 alkoxy group which may be substituted with one or more substituents selected from Substituent Group α, a C2-6 alkynyl group, a C1-6 acyl group, a C1-6 haloalkylcarbonyl group, a C1-6 alkoxycarbonyl group, a carbamoyl group, a mono(C1-6 alkyl) aminocarbonyl group, a di(C1-6 alkyl)aminocarbonyl group, a C1-6 alkylsulfonyl group, a C1-6 haloalkylsulfonyl group, a sulfamoyl group, a mono(C1-6 alkyl)aminosulfonyl group or a di(C1-6 alkyl)aminosulfonyl group,while R1 and R2 may form a 5-membered or 6-membered ring (the 5-membered or 6-membered ring is independently substituted with 1 to 4 halogen atoms or/and a C1-6 haloalkyl group) with an atom arbitrarily selected from the group consisting of a carbon atom, an oxygen atom, a nitrogen atom and a sulfur atom, together with the nitrogen atom to which R1 and R2 are bonded.
    [0007] A plant disease control agent for agricultural or horticultural use, which is characterized by containing as an active ingredient one or more compounds selected from the aminopyrimidine derivative as described in any one of Claims 2 to 6 and an agriculturally acceptable salt thereof.
    [0008] A method of using an agent, which includes applying an effective amount of one or more compounds selected from the aminopyrimidine derivative according to any one of claims 2 to 6 and an agriculturally acceptable salt thereof to target useful crops or soil, for protecting the useful crops from plant disease.
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    同族专利:
    公开号 | 公开日
    JPWO2007083692A1|2009-06-11|
    BRPI0706733A2|2011-04-05|
    WO2007083692A1|2007-07-26|
    US20090042917A1|2009-02-12|
    EP2006288A4|2010-03-10|
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