JP5851998B2 - Haloalkyl-substituted amides as insecticides and acaricides - Google Patents

Description

  The present invention relates to a novel pesticide, a process for its production and its use as an active ingredient, in particular its use as an insecticide and acaricide.

  The literature describes certain cinnamides and their use as pharmaceuticals, see for example WO-A-2002 / 096858. Surprisingly, certain amides, especially haloalkyl-substituted amides, at the same time have strong insecticidal and killing properties combined with good plant tolerance, favorable thermotoxic animal toxicity and good environmental compatibility. It was found to have tick characteristics. However, the novel compounds of the present invention are not disclosed in WO-A-2002 / 096858.

WO-A-2002 / 096858

  The present invention therefore provides the following compounds of general formula (I) and salts and N-oxides of compounds of formula (I) and their use in controlling pests in animals.

式中、
Ｒ^１は、水素、ハロゲン、ニトロ、シアノ、モノ置換されていても良いか、または同一もしくは異なるもので多置換されていても良いＣ_１−Ｃ_６−アルキル、Ｃ_２−Ｃ_６−アルケニル、Ｃ_２−Ｃ_６−アルキニル、Ｃ_１−Ｃ_６−アルコキシ、Ｃ_１−Ｃ_６−アルキルチオ、Ｃ_１−Ｃ_６−アルキルスルフィニル、Ｃ_１−Ｃ_６−アルキルスルホニル、Ｃ_３−Ｃ_６−シクロアルキル、Ｃ_１−Ｃ_６−アルキルカルボニル、Ｃ_１−Ｃ_６−アルコキシイミノ−Ｃ_１−Ｃ_６−アルキル、Ｃ_１−Ｃ_６−アルコキシカルボニル、Ｃ_１−Ｃ_６−アルキルアミノカルボニル、Ｃ_１−Ｃ_６−ジアルキルアミノカルボニル、Ｃ_１−Ｃ_６−アルキルアミノスルホニル、Ｃ_１−Ｃ_６−アルキルスルホニルアミノ、トリ（Ｃ_１−Ｃ_６−アルキル）シリル、アリール、ヘタリール、アリール−Ｃ_１−Ｃ_４−アルキルまたはヘタリール−Ｃ_１−Ｃ_４−アルキルであり、
ここで、前記置換基は、それぞれ独立にハロゲン、シアノ、ニトロ、ヒドロキシル、Ｃ_１−Ｃ_６−アルキル、Ｃ_１−Ｃ_６−アルコキシ、Ｃ_３−Ｃ_６−シクロアルキル、Ｃ_１−Ｃ_６−ハロアルコキシ、Ｃ_１−Ｃ_６−アルキルチオ、Ｃ_１−Ｃ_６−アルキルスルフェニル、Ｃ_１−Ｃ_６−アルキルスルホニル、アリール、ヘタリール、アリールアルキルまたはヘタリールアルキルから選択され、
ここで、前記アリール、ヘタリール、アリールアルキル、ヘタリールアルキル置換基は、ハロゲン、シアノ、ニトロ、ヒドロキシル、Ｃ_１−Ｃ_６−アルキル、Ｃ_２−Ｃ_６−アルケニル、Ｃ_２−Ｃ_６−アルキニル、Ｃ_３−Ｃ_６−シクロアルキル、Ｃ_１−Ｃ_６−アルコキシ、Ｃ_１−Ｃ_６−ハロアルキル、Ｃ_１−Ｃ_６−ハロアルコキシまたはＣ_１−Ｃ_６−アルキルチオによってモノ置換されていても良いか、または同一もしくは異なるもので多置換されていても良く、
または
Ｒ^１は、Ｎ、Ｓ、Ｏからなる群から１から２個のヘテロ原子を含んでも良いＣ_１−Ｃ_４炭素鎖であり、ここで、当該炭素鎖は、２個の隣接する環上の位置に結合し、Ｃ_１−Ｃ_６−アルキルまたはハロゲンによってモノ置換もしくは多置換されていても良い脂肪族、芳香族、ヘテロ芳香族または複素環を形成し、そして、この場合ｎは２であり、
ｎは、１、２または３であり、
Ｒ^２は、水素、シアノ、ヒドロキシル、アミノ、モノ置換されていても良いか、または同一もしくは異なるもので多置換されていても良いＣ_１−Ｃ_６−アルキル、Ｃ_２−Ｃ_６−アルケニル、Ｃ_２−Ｃ_６−アルキニル、Ｃ_１−Ｃ_６−アルコキシ、Ｃ_３−Ｃ_６−シクロアルキル、モノ置換されていても良いか、または同一もしくは異なるもので多置換されていても良いアリール、ヘタリールまたはモノ置換されていても良いか、または同一もしくは異なるもので多置換されていても良いアリール−Ｃ_１−Ｃ_６−アルキルまたはヘタリール−Ｃ_１−Ｃ_４−アルキルであり、
ここで、前記置換基は、それぞれ独立にハロゲン、シアノ、ニトロ、ヒドロキシル、アミノ、Ｃ_１−Ｃ_６−アルキル、Ｃ_１−Ｃ_６−アルコキシ、Ｃ_３−Ｃ_６−シクロアルキル、Ｃ_１−Ｃ_６−ハロアルコキシ、Ｃ_１−Ｃ_６−アルキルチオ、アミノ、Ｃ_１−Ｃ_６−アルキルアミノ、Ｃ_１−Ｃ_６−ジアルキルアミノ、Ｃ_１−Ｃ_４−アルキルカルボニルアミノまたはＣ_１−Ｃ_４−ジアルキルカルボニルアミノから選択され、
または
Ｒ^２は、モノ置換もしくは多置換されても良く、Ｏ、ＳまたはＮが挿入さても良いＣ_２−Ｃ_４−アルキル鎖でありここで、当該アルキル鎖は、Ｑ^１とともに、Ｏ、ＳまたはＮが挿入されても良い５から７員環を形成し、そして、その置換基は、それぞれ独立してハロゲンおよびＣ_１−Ｃ_６−アルキルから選択され、
Ｒ^３は、水素、モノ置換されていても良いか、または同一もしくは異なるもので多置換されていても良いＣ_１−Ｃ_６−アルキル、Ｃ_２−Ｃ_６−アルケニル、Ｃ_２−Ｃ_６−アルキニル、Ｃ_３−Ｃ_６−シクロアルキル、アリール−Ｃ_１−Ｃ_６−アルキル、Ｃ_１−Ｃ_６−アルキルカルボニル、Ｃ_１−Ｃ_６−アルキルスルホニル、アリールカルボニル、ヘタリールカルボニル、Ｃ_１−Ｃ_６−アルコキシカルボニルまたはアリールオキシカルボニルであり、
ここで、前記置換基は、それぞれ独立にハロゲン、シアノ、ニトロ、ヒドロキシル、Ｃ_１−Ｃ_６−アルキル、Ｃ_１−Ｃ_６−アルコキシ、Ｃ_３−Ｃ_６−シクロアルキル、Ｃ_１−Ｃ_６−ハロアルコキシ、Ｃ_１−Ｃ_６−アルキルチオ、アリール、ヘタリール、アリールアルキル、ヘタリールアルキル、Ｃ_１−Ｃ_４−アルコキシカルボニル、アミノカルボニル、Ｃ_１−Ｃ_４−アルキルアミノカルボニルまたはＣ_１−Ｃ_４−ジアルキルアミノカルボニルから選択され、
ここで、前記アリール、ヘタリール、アリールアルキル、ヘタリールアルキル置換基は、ハロゲン、シアノ、ニトロ、ヒドロキシル、Ｃ_１−Ｃ_６−アルキル、Ｃ_２−Ｃ_６−アルケニル、Ｃ_２−Ｃ_６−アルキニル、Ｃ_３−Ｃ_６−シクロアルキル、Ｃ_１−Ｃ_６−アルコキシ、Ｃ_１−Ｃ_６−ハロアルキル、Ｃ_１−Ｃ_６−ハロアルコキシまたはＣ_１−Ｃ_６−アルキルチオによってモノ置換されていても良いか、または同一もしくは異なるもので多置換されていても良く、
Ｖは、Ｒ^４であるか、または
−Ｏ−、−ＣＨ_２Ｏ−、−Ｓ−、−Ｎ（Ｒ^８）−、−Ｎ＝Ｃ（Ｒ^９）−、−Ｃ（Ｒ^９）＝Ｎ−および−Ｃ（Ｒ^９）＝Ｃ（Ｒ^１０）−から選択される二価の化学部分であり、ここで、当該二価の化学部分は単結合を介してＱ^４に結合し、そして、第２の（右側）連結部位は各場合でＱ^４に結合しており、ここで
Ｒ^４は、水素、ハロゲンまたはモノ置換されていても良いか、または同一もしくは異なるもので多置換されていても良いＣ_１−Ｃ_６−アルキルであり、ここで、前記置換基は、それぞれ独立にハロゲン、Ｃ_１−Ｃ_６−アルキルまたはＣ_１−Ｃ_６−アルコキシにから選択され、
Ｒ^８は、水素、シアノ、ヒドロキシル、モノ置換されていても良いか、または同一もしくは異なるもので多置換されていても良いＣ_１−Ｃ_６−アルキル、Ｃ_２−Ｃ_６−アルケニル、Ｃ_２−Ｃ_６−アルキニル、Ｃ_３−Ｃ_６−シクロアルキル、Ｃ_１−Ｃ_６−アルコキシ、Ｃ_１−Ｃ_６−アルキルカルボニル、アリールカルボニル、ヘタリールカルボニル、Ｃ_１−Ｃ_６−アルコキシカルボニル、アリールアルキルまたはＣ_１−Ｃ_４−アルキルスルホニルであり、
ここで、前記置換基は、それぞれ独立にハロゲン、シアノ、ニトロ、ヒドロキシル、Ｃ_１−Ｃ_６−アルキルまたはＣ_１−Ｃ_６−アルコキシ、Ｃ_１−Ｃ_４−アルコキシカルボニル、アミノ、Ｃ_１−Ｃ_６−アルキルアミノ、Ｃ_１−Ｃ_６−ジアルキルアミノ、アミノカルボニル、Ｃ_１−Ｃ_６−アルキルアミノカルボニル、Ｃ_１−Ｃ_６−ジアルキルアミノカルボニルおよびアリール−Ｃ_１−Ｃ_６−アルコキシから選択され、
Ｒ^９およびＲ^１０は、それぞれ独立に水素、ハロゲン、モノ置換されていても良いか、または、同一もしくは異なるもので多置換されていても良いＣ_１−Ｃ_６−アルキルまたはＣ_３−Ｃ_６−シクロアルキルであり、
ここで、前記置換基は、それぞれ独立にハロゲンおよびＣ_１−Ｃ_６−アルキルから選択され、
Ｒ^５は、水素、ハロゲンまたはモノ置換されていても良いか、または同一もしくは異なるもので多置換されていても良いＣ_１−Ｃ_６−アルキルまたはＣ_１−Ｃ_６−アルコキシであり、
ここで、前記置換基は、それぞれ独立にハロゲンおよびＣ_１−Ｃ_６−アルキルから選択され、
Ｒ^６は、水素、ハロゲン、ニトロ、シアノ、アミノ、ヒドロキシル、モノ置換されていても良いか、または同一もしくは異なるもので多置換されていても良いＣ_１−Ｃ_６−アルキル、Ｃ_２−Ｃ_６−アルケニル、Ｃ_２−Ｃ_６−アルキニル、Ｃ_３−Ｃ_６−シクロアルキル、Ｃ_１−Ｃ_６−アルコキシ、（Ｃ_１−Ｃ_６−アルコキシ）カルボニル、Ｃ_１−Ｃ_６−アルキルアミノ、ホルミル、（Ｃ_１−Ｃ_６−アルキル）カルボニル、Ｃ_１−Ｃ_６−アルコキシイミノ−Ｃ_１−Ｃ_６−アルキル、Ｃ_１−Ｃ_６−ジアルキルアミノ、（Ｃ_１−Ｃ_６−アルキルアミノ）カルボニル、（Ｃ_１−Ｃ_６−ジアルキルアミノ）カルボニル、Ｃ_１−Ｃ_６−アルキルチオ、Ｃ_１−Ｃ_６−アルキルスルフィニル、Ｃ_１−Ｃ_６−アルキルスルホニル、Ｃ_１−Ｃ_６−アルキルアミノスルホニル、Ｃ_１−Ｃ_６−アルキルスルホニルアミノ、アリール、ヘタリール、アリール−Ｃ_１−Ｃ_４−アルキルまたはヘタリール−Ｃ_１−Ｃ_４−アルキルであり、
ここで、前記置換基は、それぞれ独立にハロゲン、シアノ、ニトロ、ヒドロキシル、アミノ、Ｃ_１−Ｃ_６−アルキル、Ｃ_１−Ｃ_６−アルコキシ、Ｃ_３−Ｃ_６−シクロアルキル、Ｃ_１−Ｃ_６−ハロアルコキシ、Ｃ_１−Ｃ_６−アルキルチオ、アリール、ヘタリール、アリールアルキルまたはヘタリールアルキルから選択され、
ここで、前記アリール、ヘタリール、アリールアルキル、ヘタリールアルキル置換基は、ハロゲン、シアノ、ニトロ、ヒドロキシル、Ｃ_１−Ｃ_６−アルキル、Ｃ_２−Ｃ_６−アルケニル、Ｃ_２−Ｃ_６−アルキニル、Ｃ_３−Ｃ_６−シクロアルキル、Ｃ_１−Ｃ_６−アルコキシ、Ｃ_１−Ｃ_６−ハロアルキル、Ｃ_１−Ｃ_６−ハロアルコキシまたはＣ_１−Ｃ_６−アルキルチオによってモノ置換されていても良いか、または同一もしくは異なるもので多置換されていても良く、
または
Ｒ^６は、Ｎ、Ｓ、Ｏからなる群からの１から２個のヘテロ原子を含んでも良いＣ_１−Ｃ_４炭素鎖であり、ここで、当該炭素鎖は、Ｑ^４からＱ^８の２個の隣接する環上の位置に結合し、Ｃ_１−Ｃ_６−アルキルまたはハロゲンによってモノ置換もしくは多置換されても良い脂肪族、芳香族またはヘテロ芳香族環を形成し、この場合、ｍは２であり、
ｍは０、１、２、３であり、
Ｘは、さらにモノないしトリ置換されていても良いＣ_１−Ｃ_６−ハロアルキルまたはＣ_３−Ｃ_６−ハロシクロアルキルであり、ここで、その置換基は、それぞれ独立にヒドロキシル、シアノ、Ｃ_１−Ｃ_４−アルコキシ、Ｃ_１−Ｃ_４−ハロアルコキシ、Ｃ_１−Ｃ_４−アルコキシカルボニル、Ｃ_１−Ｃ_４−アルキルアミノカルボニルおよびＣ_１−Ｃ_４−ジアルキルアミノカルボニルから選択され、
Ｗは、ＯまたはＳであり、
Ａ−Ｙは、一体となってシアノであるか、モノ置換もしくは多置換されていても良いヘタリール、複素環またはオキソ複素環であり、
ここで、前記置換基は、ハロゲン、ニトロ、シアノ、アミノ、ヒドロキシルから、モノ置換されていても良いか同一もしくは異なるもので多置換されていても良いアミノ、Ｃ_１−Ｃ_６−アルキル、Ｃ_１−Ｃ_６−アルコキシ、Ｃ_１−Ｃ_６−アルコキシ−Ｃ_１−Ｃ_６−アルキル、Ｃ_１−Ｃ_６−アルキルカルボニル、Ｃ_２−Ｃ_６−アルケニル、Ｃ_２−Ｃ_６−アルキニル、Ｃ_３−Ｃ_６−シクロアルキル、アリール、ヘタリール、Ｃ_１−Ｃ_６−アリールアルキル、Ｃ_１−Ｃ_６−ヘタリールアルキル、アリールオキシ、ヘタリールオキシ、スルホニル、Ｃ_１−Ｃ_６−アルキルチオ、Ｃ_１−Ｃ_６−アルキルスルフィニル、Ｃ_１−Ｃ_６−アルキルスルホニル、Ｃ_１−Ｃ_６-アルコキシカルボニルまたはＣ_１−Ｃ_６−アルキルアミノカルボニルから選択され、
ここで、前記置換基は、それぞれ独立にハロゲン、ニトロ、シアノ、Ｃ_１−Ｃ_６−アルキル、Ｃ_１−Ｃ_６−ハロアルキル、Ｃ_１−Ｃ_６−アルコキシ、Ｃ_１−Ｃ_６−ハロアルコキシ、Ｃ_３−Ｃ_６−シクロアルキル、Ｃ_３−Ｃ_６−シクロアルキルカルボニル、Ｃ_１−Ｃ_６−アルキルチオ、Ｃ_１−Ｃ_６−アルキルスルフィニル、Ｃ_１−Ｃ_６−アルキルスルホニル、（Ｃ_１−Ｃ_６-アルコキシ）カルボニル、Ｃ_２−Ｃ_６−アルケニル、Ｃ_２−Ｃ_６−アルキニル、Ｃ_１−Ｃ_６−アルキルアミノ、Ｃ_３−Ｃ_６−シクロアルキルアミノ、（Ｃ_１−Ｃ_６−アルキル）Ｃ_３−Ｃ_６−シクロアルキルアミノまたはジ（Ｃ_１−Ｃ_４）アルキルアミノから選択され、
または
Ａは、部分−ＮＲ^１３Ｃ（＝Ｏ）−、−ＮＲ^１３Ｃ（＝Ｓ）−、−Ｃ（Ｒ^１１）（Ｒ^１２）ＮＲ^１３Ｃ（＝Ｏ）−、−Ｃ（Ｒ^１１）（Ｕ）ＮＲ^１３Ｃ（＝Ｏ）−、−Ｃ（Ｒ^１１）（Ｒ^１２）Ｎ（Ｕ）Ｃ（＝Ｏ）−、−Ｃ（Ｒ^１１）（Ｒ^１２）ＮＲ^１３Ｃ（＝Ｓ）−、−Ｃ（＝Ｏ）ＮＲ^１３−、−Ｃ（＝Ｏ）ＮＲ^１３ＣＨ_２−、−Ｃ（＝Ｓ）ＮＲ^１３−、−Ｃ（＝Ｓ）ＮＲ^１３ＣＨ_２−、−Ｃ（＝Ｏ）ＮＲ^１３Ｃ（Ｒ^１１）＝Ｎ−Ｏ−、−Ｃ（Ｒ^１１）＝Ｎ−Ｏ−、−Ｃ（ＮＨ_２）＝Ｎ−Ｏ−、−Ｃ（Ｒ^１１）＝Ｎ−ＯＣＨ_２Ｃ（＝Ｏ）ＮＲ^１３−、−Ｃ（Ｒ^１１）（Ｒ^１２）ＮＲ^１３Ｃ（＝Ｏ）ＮＲ^１４−、−Ｃ（Ｒ^１１）（Ｒ^１２）ＮＲ^１３Ｃ（＝Ｏ）ＣＨ_２Ｓ−、−ＮＲ^１３（Ｃ＝Ｏ）ＮＲ^１４−、−Ｃ（＝Ｏ）−、−Ｃ（＝Ｎ−Ｏ−Ｒ^１３）−、−Ｃ（＝Ｏ）Ｏ−、−Ｃ（＝Ｏ）ＯＣＨ_２Ｃ（＝Ｏ）−、−Ｃ（＝Ｏ）ＯＣＨ_２Ｃ（＝Ｏ）ＮＲ^１３−、−Ｃ（＝Ｏ）ＮＲ^１３ＣＨ_２Ｃ（＝Ｏ）ＮＲ^１４−、−Ｃ（＝Ｏ）ＮＲ^１３ＣＨ_２Ｃ（＝Ｏ）−、−Ｃ（＝Ｏ）ＮＲ^１３ＣＨ_２Ｃ（＝Ｏ）Ｏ−、−Ｃ（＝Ｏ）ＮＲ^１３ＮＲ^１４Ｃ（＝Ｏ）−、−Ｃ（＝Ｏ）ＮＲ^１３ＮＲ^１４−、−Ｎ（Ｒ^１３）−、−Ｃ（Ｒ^１１）（Ｒ^１２）ＮＲ^１３−、−Ｓ（＝Ｏ）_ｐ−、−Ｓ（＝Ｏ）_２ＮＲ^１３−、−ＮＲ^１３Ｓ（＝Ｏ）_２−、−Ｃ（Ｒ^１１）（Ｒ^１２）ＮＲ^１３Ｓ（＝Ｏ）_２−、−ＳＯ（＝Ｎ−ＣＮ）−、−Ｓ（＝Ｎ−ＣＮ）−、−Ｃ（＝Ｏ）ＮＨＳ（＝Ｏ）_２−、−Ｃ（＝Ｏ）Ｎ（Ｒ^１３）−Ｏ−、−Ｃ（＝Ｏ）ＣＨ（ＣＮ）−または−ＣＨ（ＣＮ）ＮＲ^１３−から選択される二価の化学部分であり、ここで、当該二価の化学部分における第１の（左側）連結部位は、位置Ｑ^４からＱ^８のうちの１箇所で環に、第２の（右側）連結部位はＹに連結されており、ここで
Ｕは、位置Ｑ^４からＱ^８での環へのＡの連結部位に隣接する炭素原子とともに、５から７員環を形成する置換されていても良いＣ_２−Ｃ_４−アルキルであり、
ここで、前記置換基は、それぞれ独立にＣ_１−Ｃ_３−アルキル、Ｃ_１−Ｃ_３−アルコキシおよびハロゲンから選択され、ここで
ｐは、０、１または２の値を取っても良く、ここで
Ｒ^１１およびＲ^１２は、それぞれ独立に水素、シアノまたはモノ置換されていても良いか、または同一もしくは異なるもので多置換されていても良いＣ_１−Ｃ_４−アルキルまたはＣ_３−Ｃ_６−シクロアルキルであり、
ここで、前記置換基は、それぞれ独立にハロゲン、シアノ、ニトロ、ヒドロキシル、Ｃ_１−Ｃ_６−アルキルおよびＣ_１−Ｃ_６−アルコキシから選択され、
または
Ｒ^１１とＲ^１２は、一体となって１から２個の二重結合を有していても良い３から６員環を形成しているＣ_２−Ｃ_５−アルキルまたはＣ_３−Ｃ_５−アルケニルであり、
あるいは
Ｒ^１１とＲ^１３は、一体となって１から２個の二重結合を含んでいても良い３から７員環を形成しているＣ_２−Ｃ_５−アルキルまたはＣ_３−Ｃ_５−アルケニルであり、
そして、ここで
Ｒ^１３およびＲ^１４は、それぞれ独立に水素、モノ置換されていても良いか、または同一もしくは異なるもので多置換されていても良いＣ_１−Ｃ_６−アルキルまたはＣ_３−Ｃ_６−シクロアルキル、Ｃ_１−Ｃ_６−アルキルカルボニル、Ｃ_１−Ｃ_６−アルコキシカルボニルまたはアリールオキシカルボニルであり、
ここで、前記置換基は、それぞれ独立にハロゲン、シアノ、ニトロ、ヒドロキシル、Ｃ_１−Ｃ_６−アルキルまたはＣ_１−Ｃ_６−アルコキシから選択され、
または
Ｒ^１３とＲ^１４は、一体となって１から２個の二重結合を有していても良い３から７員環を形成しているＣ_２−Ｃ_５−アルキルまたはＣ_３−Ｃ_５−アルケニルであり、
Ｙは、水素、モノ置換されていても良いか、または同一もしくは異なるもので多置換されていても良いＣ_１−Ｃ_６−アルキル、Ｃ_２−Ｃ_６−アルケニル、Ｃ_２−Ｃ_６−アルキニル、Ｃ_３−Ｃ_６−シクロアルキル、Ｃ_３−Ｃ_６−シクロアルケニル、アリール、ヘタリール、複素環またはオキソ複素環であり、
ここで、前記置換基は、ハロゲン、ニトロ、シアノ、ヒドロキシルから、モノ置換されていても良いか同一もしくは異なるもので多置換されていても良いアミノ、Ｃ_１−Ｃ_６−アルキル、Ｃ_２−Ｃ_６−アルケニル、Ｃ_２−Ｃ_６−アルキニル、Ｃ_３−Ｃ_６−シクロアルキル、Ｃ_１−Ｃ_６−アルキルカルボニル、Ｃ_１−Ｃ_６−アルコキシ、Ｃ_１−Ｃ_６−アルコキシカルボニル、Ｃ_１−Ｃ_６−アルキルチオ、Ｃ_１−Ｃ_６−アルキルスルフィニル、Ｃ_１−Ｃ_６−アルキルスルホニル、Ｃ_１−Ｃ_６−アルコキシカルボニル、Ｃ_１−Ｃ_６−アルキルアミノカルボニル、Ｃ_１−Ｃ_６−ジアルキルアミノカルボニル、Ｃ_１−Ｃ_６−アルキルアミノスルホニル、Ｃ_１−Ｃ_６−アルキルスルホニルアミノ、アリール、ヘタリール、Ｃ_１−Ｃ_６−アリールアルキル、Ｃ_１−Ｃ_６−ヘタリールアルキル、アリールオキシ、ヘタリールオキシまたは複素環、Ｃ_１−Ｃ_６−アルコキシ、Ｃ_１−Ｃ_６−アルキル、Ｃ_１−Ｃ_６−アルキルカルボニル、スルホニル、スルフィニル、Ｃ_１−Ｃ_６−アルキルチオまたはＣ_１−Ｃ_６−アルコキシカルボニルから選択され、
ここで、前記置換基は、それぞれ独立にハロゲン、Ｃ_１−Ｃ_６−アルキル、ヒドロキシル、アミノ、Ｃ_１−Ｃ_６−アルキルカルボニル、Ｃ_１−Ｃ_６−ハロアルキル、Ｃ_１−Ｃ_６−アルコキシ、Ｃ_１−Ｃ_６−ハロアルコキシ、Ｃ_３−Ｃ_６−シクロアルキル、Ｃ_３−Ｃ_６−シクロアルキルカルボニル、シアノ、ニトロ、Ｃ_１−Ｃ_６−アルキルチオ、Ｃ_１−Ｃ_６−アルキルスルフィニル、Ｃ_１−Ｃ_６−アルキルスルホニル、（Ｃ_１−Ｃ_６−アルコキシ）カルボニル、Ｃ_２−Ｃ_６−アルケニル、Ｃ_２−Ｃ_６−アルキニル、Ｃ_１−Ｃ_６−アルキルアミノ、Ｃ_３−Ｃ_６−シクロアルキルアミノ、（Ｃ_１−Ｃ_６−アルキル）Ｃ_３−Ｃ_６−シクロアルキルアミノ、ジ（Ｃ_１−Ｃ_４）アルキルアミノまたはＣ_１−Ｃ_６−アルキルアミノカルボニルから選択され、
Ｑ^１からＱ^３は、それぞれ独立に水素もしくはＲ^１によって置換された炭素原子であるか、またはＮであり、ここで、Ｑ^１からＱ^３における窒素原子の数は２以下であり、
Ｑ^４は、水素もしくはＲ^６によって置換されているか、Ｖに結合している炭素原子（その場合に、ＶはＲ^４以外である）であるか、またはＮであり、
Ｑ^５からＱ^８は、それぞれ独立に水素、Ｒ^６もしくはＡ−Ｙによって置換された炭素原子であるか、またはＮであり、ここで、Ｑ^４からＱ^８における窒素原子の数は、２以下であり、そして、Ｑ^５、Ｑ^６、Ｑ^７、Ｑ^８のうちの正確に１個がＡ−Ｙによって置換されている。

Where
R ¹ is hydrogen, halogen, nitro, cyano, C ₁ -C ₆ -alkyl, C ₂ -C ₆ -alkenyl, which may be mono-substituted or poly-substituted with the same or different ones, C ₂ -C ₆ - _alkynyl, C 1 -C ₆ - _alkoxy, C 1 -C ₆ - _alkylthio, C 1 -C ₆ - _{alkylsulfinyl,} C 1 -C ₆ - _{alkylsulfonyl,} C 3 -C ₆ - cycloalkyl C ₁ -C ₆ -alkylcarbonyl, C ₁ -C ₆ -alkoxyimino-C ₁ -C ₆ -alkyl, C ₁ -C ₆ -alkoxycarbonyl, C ₁ -C ₆ -alkylaminocarbonyl, C ₁ -C ₆ - _{dialkylaminocarbonyl,} C 1 -C ₆ - alkyl _{aminosulfonyl,} C 1 -C ₆ - alkylsulfonylamino, tri _(C 1 -C - alkyl) silyl, aryl, hetaryl, aryl _-C 1 -C ₄ - alkyl or hetaryl _-C 1 -C ₄ - alkyl,
Wherein said substituents are halogen independently, cyano, nitro, _hydroxyl, C 1 -C ₆ - _alkyl, C 1 -C ₆ - _alkoxy, C 3 -C ₆ - _cycloalkyl, C 1 -C ₆ - Selected from haloalkoxy, C ₁ -C ₆ -alkylthio, C ₁ -C ₆ -alkylsulfenyl, C ₁ -C ₆ -alkylsulfonyl, aryl, hetaryl, arylalkyl or hetarylalkyl;
Wherein the aryl, hetaryl, arylalkyl, hetarylalkyl substituents are halogen, cyano, nitro, hydroxyl, C ₁ -C ₆ -alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, C ₃ -C ₆ - or may be monosubstituted by alkylthio - _cycloalkyl, C 1 -C ₆ - _alkoxy, C 1 -C ₆ - _haloalkyl, C 1 -C ₆ - haloalkoxy or _C 1 -C ₆ Or may be poly-substituted with the same or different,
Or R ¹ is a C ₁ -C ₄ carbon chain that may contain 1 to 2 heteroatoms from the group consisting of N, S, O, wherein the carbon chain is on two adjacent rings. To form an aliphatic, aromatic, heteroaromatic or heterocyclic ring which may be mono- or polysubstituted by C ₁ -C ₆ -alkyl or halogen, and in this case n is 2 Yes,
n is 1, 2 or 3;
R ² is hydrogen, cyano, hydroxyl, amino, C ₁ -C ₆ -alkyl, C ₂ -C ₆ -alkenyl, which may be mono-substituted or the same or different and may be poly-substituted, C ₂ -C ₆ -alkynyl, C ₁ -C ₆ -alkoxy, C ₃ -C ₆ -cycloalkyl, aryl, hetaryl, which may be mono-substituted or poly-substituted with the same or different ones Or aryl-C ₁ -C ₆ -alkyl or hetaryl-C ₁ -C ₄ -alkyl which may be mono-substituted or may be poly-substituted with the same or different ones,
Here, the substituents are independently halogen, cyano, nitro, hydroxyl, amino, C ₁ -C ₆ -alkyl, C ₁ -C ₆ -alkoxy, C ₃ -C ₆ -cycloalkyl, C ₁ -C. ₆ - _haloalkoxy, C 1 -C ₆ - alkylthio, _amino, C 1 -C ₆ - _alkylamino, C 1 -C ₆ - _{dialkylamino,} C 1 -C ₄ - alkylcarbonylamino or _C 1 -C ₄ - dialkyl Selected from carbonylamino,
Or R ² is a C ₂ -C ₄ -alkyl chain which may be mono- or poly-substituted and O, S or N may be inserted, wherein the alkyl chain together with Q ¹ is O, S Or N may be inserted to form a 5- to 7-membered ring, and the substituents are each independently selected from halogen and C ₁ -C ₆ -alkyl;
R ³ is hydrogen, mono-substituted, or C ₁ -C ₆ -alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C _6- , which may be mono-substituted or the same or different. _alkynyl, C 3 -C ₆ - cycloalkyl, aryl _-C 1 -C ₆ - _alkyl, C 1 -C ₆ - _{alkylcarbonyl,} C 1 -C ₆ - alkylsulfonyl, arylcarbonyl, _{hetarylcarbonyl,} C 1 -C ₆ -alkoxycarbonyl or aryloxycarbonyl,
Wherein said substituents are halogen independently, cyano, nitro, _hydroxyl, C 1 -C ₆ - _alkyl, C 1 -C ₆ - _alkoxy, C 3 -C ₆ - _cycloalkyl, C 1 -C ₆ - _haloalkoxy, C 1 -C ₆ - alkylthio, aryl, hetaryl, arylalkyl, _{hetarylalkyl,} C 1 -C ₄ - alkoxycarbonyl, _{aminocarbonyl,} C 1 -C ₄ - alkylaminocarbonyl or _C 1 -C ₄ - Selected from dialkylaminocarbonyl,
Wherein the aryl, hetaryl, arylalkyl, hetarylalkyl substituents are halogen, cyano, nitro, hydroxyl, C ₁ -C ₆ -alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, C ₃ -C ₆ - or may be monosubstituted by alkylthio - _cycloalkyl, C 1 -C ₆ - _alkoxy, C 1 -C ₆ - _haloalkyl, C 1 -C ₆ - haloalkoxy or _C 1 -C ₆ Or may be poly-substituted with the same or different,
V is R ⁴ , or —O—, —CH ₂ O—, —S—, —N (R ⁸ ) —, —N═C (R ⁹ ) —, —C (R ⁹ ) = N A divalent chemical moiety selected from-and -C (R ⁹ ) = C (R ¹⁰ )-, wherein the divalent chemical moiety is bonded to Q ⁴ via a single bond, and The second (right side) linking moiety is in each case bound to Q ⁴ , where R ⁴ may be hydrogen, halogen or mono-substituted, or poly-substituted with the same or different. C ₁ -C ₆ -alkyl, wherein the substituents are each independently selected from halogen, C ₁ -C ₆ -alkyl or C ₁ -C ₆ -alkoxy,
R ⁸ is hydrogen, cyano, hydroxyl, C ₁ -C ₆ -alkyl, C ₂ -C ₆ -alkenyl, C ₂ which may be mono-substituted or poly-substituted with the same or different ones. -C ₆ - _alkynyl, C 3 -C ₆ - _cycloalkyl, C 1 -C ₆ - _alkoxy, C 1 -C ₆ - alkylcarbonyl, arylcarbonyl, _{hetarylcarbonyl,} C 1 -C ₆ - alkoxycarbonyl, arylalkyl Or C ₁ -C ₄ -alkylsulfonyl,
Here, the substituent is independently halogen, cyano, nitro, hydroxyl, C ₁ -C ₆ -alkyl or C ₁ -C ₆ -alkoxy, C ₁ -C ₄ -alkoxycarbonyl, amino, C ₁ -C. ₆ - _alkylamino, C 1 -C ₆ - is selected from alkoxy, - dialkylamino, _{aminocarbonyl,} C 1 -C ₆ - _{alkylaminocarbonyl,} C 1 -C ₆ - dialkylaminocarbonyl and aryl _-C 1 -C ₆
R ⁹ and R ¹⁰ are each independently hydrogen, halogen, mono-substituted, or C ₁ -C ₆ -alkyl or C ₃ -C ₆ which may be poly-substituted with the same or different ones. -Cycloalkyl,
Wherein the substituents are each independently selected from halogen and C ₁ -C ₆ -alkyl;
R ⁵ is hydrogen, halogen or C ₁ -C ₆ -alkyl or C ₁ -C ₆ -alkoxy, which may be mono-substituted, poly-substituted with the same or different,
Wherein the substituents are each independently selected from halogen and C ₁ -C ₆ -alkyl;
R ⁶ is hydrogen, halogen, nitro, cyano, amino, hydroxyl, mono-substituted, or C ₁ -C ₆ -alkyl, C ₂ -C, which may be poly-substituted with the same or different ones ₆ - _alkenyl, C 2 -C ₆ - _alkynyl, C 3 -C ₆ - _cycloalkyl, C 1 -C ₆ - _{alkoxy, (C} 1 -C ₆ - alkoxy) _carbonyl, C 1 -C ₆ - alkylamino, formyl , (C ₁ -C ₆ -alkyl) carbonyl, C ₁ -C ₆ -alkoxyimino-C ₁ -C ₆ -alkyl, C ₁ -C ₆ -dialkylamino, (C ₁ -C ₆ -alkylamino) carbonyl, _(C 1 -C ₆ - dialkylamino) _carbonyl, C 1 -C ₆ - _alkylthio, C 1 -C ₆ - _{alkylsulfinyl,} C 1 -C ₆ - alkyl _Sulfonyl, C 1 -C ₆ - alkyl _{aminosulfonyl,} C 1 -C ₆ - alkylsulfonylamino, aryl, hetaryl, aryl _-C 1 -C ₄ - alkyl or hetaryl _-C 1 -C ₄ - alkyl,
Here, the substituents are independently halogen, cyano, nitro, hydroxyl, amino, C ₁ -C ₆ -alkyl, C ₁ -C ₆ -alkoxy, C ₃ -C ₆ -cycloalkyl, C ₁ -C. Selected from ₆ -haloalkoxy, C ₁ -C ₆ -alkylthio, aryl, hetaryl, arylalkyl or hetarylalkyl;
Wherein the aryl, hetaryl, arylalkyl, hetarylalkyl substituents are halogen, cyano, nitro, hydroxyl, C ₁ -C ₆ -alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, C ₃ -C ₆ - or may be monosubstituted by alkylthio - _cycloalkyl, C 1 -C ₆ - _alkoxy, C 1 -C ₆ - _haloalkyl, C 1 -C ₆ - haloalkoxy or _C 1 -C ₆ Or may be poly-substituted with the same or different,
Or R ⁶ is a C ₁ -C ₄ carbon chain that may contain 1 to 2 heteroatoms from the group consisting of N, S, O, wherein the carbon chain is of Q ⁴ to Q ⁸ Bonded to a position on two adjacent rings to form an aliphatic, aromatic or heteroaromatic ring which may be mono- or polysubstituted by C ₁ -C ₆ -alkyl or halogen, where m Is 2,
m is 0, 1, 2, 3,
X is C ₁ -C ₆ -haloalkyl or C ₃ -C ₆ -halocycloalkyl which may be further mono- or tri-substituted, wherein the substituents are each independently hydroxyl, cyano, C ₁ -C ₄ - _alkoxy, C 1 -C ₄ - _haloalkoxy, C 1 -C ₄ - _{alkoxycarbonyl,} C 1 -C ₄ - alkylaminocarbonyl and _C 1 -C ₄ - is selected from dialkylaminocarbonyl,
W is O or S;
AY is hetaryl, heterocycle or oxoheterocycle which may be cyano together or mono- or poly-substituted,
Here, the substituent is a halogen, nitro, cyano, amino, hydroxyl, which may be mono-substituted or the same or different, and may be poly-substituted amino, C ₁ -C ₆ -alkyl, C ₁ -C ₆ - _alkoxy, C 1 -C ₆ - alkoxy _-C 1 -C ₆ - _alkyl, C 1 -C ₆ - _{alkylcarbonyl,} C 2 -C ₆ - _alkenyl, C 2 -C ₆ - alkynyl, _{C 3} -C ₆ - cycloalkyl, aryl, _hetaryl, C 1 -C ₆ - _arylalkyl, C 1 -C ₆ - hetarylalkyl, aryloxy, hetaryloxy, _sulfonyl, C 1 -C ₆ - alkylthio, _{C 1} - C ₆ - _{alkylsulfinyl,} C 1 -C ₆ - _{alkylsulfonyl, C} 1 -C 6 _- alkoxycarbonyl or _C 1 -C ₆ - A Selected from rualkylaminocarbonyl,
Here, each of the substituents is independently halogen, nitro, cyano, C ₁ -C ₆ -alkyl, C ₁ -C ₆ -haloalkyl, C ₁ -C ₆ -alkoxy, C ₁ -C ₆ -haloalkoxy, C ₃ -C ₆ - _cycloalkyl, C 3 -C ₆ - _{cycloalkylcarbonyl,} C 1 -C ₆ - _alkylthio, C 1 -C ₆ - _{alkylsulfinyl,} C 1 -C ₆ - _{alkylsulfonyl, (C} 1 -C ₆ - alkoxy) _carbonyl, C 2 -C ₆ - _alkenyl, C 2 -C ₆ - _alkynyl, C 1 -C ₆ - _alkylamino, C 3 -C ₆ - _{cycloalkylamino, (C} 1 -C ₆ - alkyl) C ₃ -C ₆ - is selected from cycloalkylamino or di _(C 1 -C ₄₎ alkylamino,
Or A is a moiety —NR ¹³ C (═O) —, —NR ¹³ C (═S) —, —C (R ¹¹ ) (R ¹² ) NR ¹³ C (═O) —, —C (R ¹¹ ) (U) NR ¹³ C (═O) —, —C (R ¹¹ ) (R ¹² ) N (U) C (═O) —, —C (R ¹¹ ) (R ¹² ) NR ¹³ C (= S) ^{-, - C (= O)} NR 13 -, - C (= O) NR 13 CH 2 -, - C (= S) NR 13 -, - C (= S) NR 13 CH 2 -, - C (= O) NR ¹³ C (R ¹¹ ) = N—O—, —C (R ¹¹ ) = N—O—, —C (NH ₂ ) = N—O—, —C (R ¹¹ ) = N—OCH ₂ ^{C (= O) NR 13 -} , - C (R 11) (R 12) NR 13 C (= O) NR 14 -, - C (R 11) (R 12) NR 13 C (= O) CH 2 S ^-, - ^NR 13 (C ^{O) NR 14 -, - C} (= O) -, - C (= N-O-R 13) -, - C (= O) O -, - C (= O) OCH 2 C (= O) - ^{_{, -C (= O) OCH 2}} C (= O) NR 13 -, - C (= O) NR 13 CH 2 C (= O) NR 14 -, - C (= O) NR 13 CH 2 C (= O) —, —C (═O) NR ¹³ CH ₂ C (═O) O—, —C (═O) NR ¹³ NR ¹⁴ C (═O) —, —C (═O) NR ¹³ NR ¹⁴ — ^{, -N (R 13) -,} - C (R 11) (R 12) NR 13 -, - S (= O) p -, - S (= O) 2 NR 13 -, - NR 13 S (= O ) _2- , -C (R ¹¹ ) (R ¹² ) NR ¹³ S (= O) _2- , -SO (= N-CN)-, -S (= N-CN)-, -C (= O) _{NHS (= O) 2 -,} - C (= O) N ( ^{13) -O -, - C (} = O) CH (CN) - or -CH (CN) ^{NR 13} - a divalent chemical moiety selected from wherein, the in the chemical portion of the divalent 1 's (left) connecting portion, the ring in one location of the Q ⁸ from the position Q ^4, the second (right) connecting portion is connected to Y, where U is, Q ⁸ from the position Q ⁴ together with the carbon atom adjacent to the linking site a to ring, the optionally substituted to form a 5 to 7-membered ring C ₂ -C 4 _- alkyl,
Wherein said substituents are each independently _C 1 -C ₃ - _alkyl, C 1 -C ₃ - is selected from alkoxy and halogen, where p may take the values 0, 1 or 2, Here, R ¹¹ and R ¹² are each independently hydrogen, cyano or mono-substituted, or C ₁ -C ₄ -alkyl or C ₃ -C which may be poly-substituted with the same or different ones. ₆ -cycloalkyl;
Wherein the substituents are each independently selected from halogen, cyano, nitro, hydroxyl, C ₁ -C ₆ -alkyl and C ₁ -C ₆ -alkoxy,
Or R ¹¹ and R ¹² together may have 1 to 2 double bonds and may form a 3 to 6 membered ring, C ₂ -C ₅ -alkyl or C ₃ -C ₅ -Alkenyl,
Alternatively R ¹¹ and ^{R 13} are, _C 2 -C ₅ forming two double bonds contain an 3 to 7-membered ring may be from 1 together - alkyl or _C 3 -C ₅ - Alkenyl,
R ¹³ and R ¹⁴ are each independently hydrogen, C ₁ -C ₆ -alkyl or C ₃ -C which may be mono-substituted, or may be poly-substituted with the same or different ones. ₆ -cycloalkyl, C ₁ -C ₆ -alkylcarbonyl, C ₁ -C ₆ -alkoxycarbonyl or aryloxycarbonyl,
Wherein the substituents are each independently selected from halogen, cyano, nitro, hydroxyl, C ₁ -C ₆ -alkyl or C ₁ -C ₆ -alkoxy,
Or R ¹³ and R ¹⁴ together may have 1 to 2 double bonds and form a 3 to 7-membered ring C ₂ -C ₅ -alkyl or C ₃ -C ₅ -Alkenyl,
Y is hydrogen, mono-substituted, or C ₁ -C ₆ -alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl which may be the same or different and multi-substituted. C ₃ -C ₆ -cycloalkyl, C ₃ -C ₆ -cycloalkenyl, aryl, hetaryl, heterocycle or oxoheterocycle,
Here, the substituent is halogen, nitro, cyano, hydroxyl, which may be mono-substituted or the same or different and may be poly-substituted amino, C ₁ -C ₆ -alkyl, C _2- C ₆ - _alkenyl, C 2 -C ₆ - _alkynyl, C 3 -C ₆ - _cycloalkyl, C 1 -C ₆ - _{alkylcarbonyl,} C 1 -C ₆ - _alkoxy, C 1 -C ₆ - alkoxycarbonyl, _{C 1} -C ₆ - _alkylthio, C 1 -C ₆ - _{alkylsulfinyl,} C 1 -C ₆ - _{alkylsulfonyl,} C 1 -C ₆ - _{alkoxycarbonyl,} C 1 -C ₆ - _{alkylaminocarbonyl,} C 1 -C ₆ - dialkyl _{aminocarbonyl,} C 1 -C ₆ - alkyl _{aminosulfonyl,} C 1 -C ₆ - alkylsulfonylamino, aryl, f _Reel, C 1 -C ₆ - _arylalkyl, C 1 -C ₆ - hetarylalkyl, aryloxy, hetaryloxy or _{heterocyclic,} C 1 -C ₆ - _alkoxy, C 1 -C ₆ - alkyl, _{C 1} - C ₆ - is selected from alkoxycarbonyl, - alkylcarbonyl, sulfonyl, _sulfinyl, C 1 -C ₆ - alkylthio or _C 1 -C ₆
Here, each of the substituents is independently halogen, C ₁ -C ₆ -alkyl, hydroxyl, amino, C ₁ -C ₆ -alkylcarbonyl, C ₁ -C ₆ -haloalkyl, C ₁ -C ₆ -alkoxy, C ₁ -C ₆ -haloalkoxy, C ₃ -C ₆ -cycloalkyl, C ₃ -C ₆ -cycloalkylcarbonyl, cyano, nitro, C ₁ -C ₆ -alkylthio, C ₁ -C ₆ -alkylsulfinyl, C ₁ -C ₆ - _{alkylsulfonyl, (C} 1 -C ₆ - alkoxy) _carbonyl, C 2 -C ₆ - _alkenyl, C 2 -C ₆ - _alkynyl, C 1 -C ₆ - _alkylamino, C 3 -C ₆ - Cycloalkylamino, (C ₁ -C ₆ -alkyl) C ₃ -C ₆ -cycloalkylamino, di (C ₁ -C ₄ ) alkylamino or C ₁ -C ₆ - is selected from alkyl aminocarbonyl,
Q ¹ to Q ³ are each independently a hydrogen atom or a carbon atom substituted by R ¹ or N, wherein the number of nitrogen atoms in Q ¹ to Q ³ is 2 or less,
Q ⁴ is hydrogen or carbon atom substituted by R ⁶ , bonded to V (in which case V is other than R ⁴ ), or N;
Q ⁵ to Q ⁸ are each independently a carbon atom substituted by hydrogen, R ⁶ or AY, or N, where the number of nitrogen atoms in Q ⁴ to Q ⁸ is 2 or less And exactly one of Q ⁵ , Q ⁶ , Q ⁷ , Q ⁸ is replaced by AY.

  The compounds of formula (I) may be present in different polymorphs or as a mixture of different polymorphs where appropriate. Both pure polymorphs and polymorphic mixtures form part of the subject matter of the present invention and can be used according to the present invention.

  The compounds of formula (I) include any diastereomers or enantiomers present, as well as E / Z isomers.

  Here, the substituted acrylamide is generally defined by the formula (I). Definitions of preferred groups of the formulas specifically described above and below are provided below. These definitions apply equally to the final product of formula (I) and all intermediates.

Preferred, more preferred and most preferred compounds of formula (I), as well as preferred, more preferred and most preferred compounds of formula (I) are pest control methods comprising:
R ¹ Are preferably hydrogen, halogen, nitro, cyano, monosubstituted, or polysubstituted with the same or different ₁ -C ₄ -Alkyl, C ₂ -C ₆ -Alkenyl, C ₂ -C ₄ -Alkynyl, C ₁ -C ₄ -Alkoxy, C ₁ -C ₄ -Alkylthio, C ₁ -C ₄ -Alkylsulfinyl, C ₁ -C ₄ -Alkylsulfonyl, C ₃ -C ₄ -Cycloalkyl, C ₁ -C ₄ -Alkylcarbonyl, C ₁ -C ₄ -Alkoxycarbonyl, C ₁ -C ₄ -Alkylaminocarbonyl, C ₁ -C ₄ -Dialkylaminocarbonyl or C ₁ -C ₄ -Alkylaminosulfonyl,
Here, the substituents are independently halogen, cyano, nitro, hydroxyl, C ₁ -C ₄ -Alkyl, C ₁ -C ₄ -Alkoxy, C ₃ -C ₄ -Cycloalkyl, C ₁ -C ₄ -Haloalkoxy and C ₁ -C ₄ -Selected from alkylthio;
n is preferably 1, 2 or 3;
R ² Is preferably hydrogen, cyano, hydroxyl, amino, monosubstituted or optionally trisubstituted with the same or different ₁ -C ₄ -Alkyl, C ₂ -C ₄ -Alkenyl, C ₂ -C ₄ -Alkynyl, C ₁ -C ₄ -Alkoxy or C ₃ -C ₆ -Cycloalkyl,
Here, the substituent is independently halogen, cyano, nitro, hydroxyl, amino, C ₁ -C ₄ -Alkyl and C ₁ -C ₄ -Selected from alkoxy
R ³ Are preferably hydrogen, monosubstituted, or polysubstituted with the same or different ₁ -C ₄ -Alkyl, C ₂ -C ₄ -Alkenyl, C ₂ -C ₄ -Alkynyl, C ₃ -C ₄ -Cycloalkyl, aryl-C ₁ -C ₄ -Alkyl, C ₁ -C ₄ -Alkylcarbonyl, C ₁ -C ₄ -Alkylsulfonyl, arylcarbonyl, hetarylcarbonyl, C ₁ -C ₄ -Alkoxycarbonyl or aryloxycarbonyl,
Here, the substituents are independently halogen, cyano, nitro, hydroxyl, C ₁ -C ₆ -Alkyl, C ₁ -C ₆ -Alkoxy, C ₃ -C ₆ -Cycloalkyl, C ₁ -C ₆ -Haloalkoxy, C ₁ -C ₆ -Alkylthio, C ₁ -C ₄ -Alkoxycarbonyl, aminocarbonyl, C ₁ -C ₄ -Alkylaminocarbonyl and C ₁ -C ₄ -Selected from dialkylaminocarbonyl,
V is preferably R ⁴ Or
Or -O-, -S-, -N (R ⁸ )-, -C (R ⁹ ) = N-, -N = C (R ⁹ )-And -C (R ⁹ ) = C (R ¹⁰ )-, Wherein the divalent chemical moiety is selected from Q through a single bond. ⁴ And the second (right side) linking site is in each case Q ⁴ Where:
R ⁴ Is preferably hydrogen, halogen or monosubstituted or optionally polysubstituted with the same or different ₁ -C ₄ -Alkyl, wherein the substituents are each independently halogen, C ₁ -C ₄ -Alkyl and C ₁ -C ₄ -Selected from alkoxy
R ⁸ Are preferably hydrogen, cyano, hydroxyl, monosubstituted, or polysubstituted with the same or different ₁ -C ₄ -Alkyl, C ₂ -C ₆ -Alkenyl, C ₂ -C ₆ -Alkynyl, C ₃ -C ₆ -Cycloalkyl, C ₁ -C ₄ -Alkoxy, C ₁ -C ₆ -Alkoxycarbonyl, arylalkyl or C ₁ -C ₄ -Alkylcarbonyl;
Here, the substituents are independently halogen, cyano, nitro, hydroxyl, C ₁ -C ₆ -Alkyl, C ₁ -C ₆ -Alkoxy, C ₁ -C ₄ -Alkoxycarbonyl, aminocarbonyl, C ₁ -C ₄ -Alkylaminocarbonyl or C ₁ -C ₄ -Dialkylaminocarbonyl and aryl-C ₁ -C ₄ -Selected from alkoxy
R ⁹ And R ¹⁰ Are preferably each independently hydrogen, halogen, or monosubstituted, or polysubstituted with the same or different ₁ -C ₄ -Alkyl,
Wherein the substituents are independently halogen, cyano and C ₁ -C ₆ -Selected from alkyl,
R ⁵ Are preferably hydrogen, halogen or mono-substituted, or C which may be poly-substituted with the same or different ₁ -C ₄ -Alkyl, wherein the substituents are each independently halogen, C ₁ -C ₄ -Alkyl or C ₁ -C ₄ -Selected from alkoxy
R ⁶ Is preferably hydrogen, halogen, nitro, cyano, amino, hydroxyl, monosubstituted or polysubstituted with the same or different ₁ -C ₄ -Alkyl, C ₂ -C ₄ -Alkenyl, C ₂ -C ₄ -Alkynyl, C ₃ -C ₅ -Cycloalkyl, C ₁ -C ₄ -Alkoxy, (C ₁ -C ₄ -Alkoxy) carbonyl, C ₁ -C ₄ -Alkylamino, formyl, (C ₁ -C ₄ -Alkyl) carbonyl, C ₁ -C ₄ -Alkoxyimino-C ₁ -C ₄ -Alkyl, C ₁ -C ₄ -Dialkylamino, (C ₁ -C ₄ -Alkylamino) carbonyl, (C ₁ -C ₄ -Dialkylamino) carbonyl, C ₁ -C ₄ -Alkylthio, C ₁ -C ₄ -Alkylsulfinyl, C ₁ -C ₄ -Alkylsulfonyl, C ₁ -C ₄ -Alkylaminosulfonyl or C ₁ -C ₄ -Alkylsulfonylamino,
Here, the substituent is independently halogen, cyano, nitro, hydroxyl, amino, C ₁ -C ₆ -Alkyl, C ₁ -C ₆ -Alkoxy, C ₃ -C ₆ -Cycloalkyl, C ₁ -C ₆ -Haloalkoxy and C ₁ -C ₆ -Selected from alkylthio;
Or
R ⁶ May preferably contain 1 to 2 heteroatoms from the group consisting of N, S, O. ₁ -C ₄ A carbon chain, wherein the carbon chain is located at position Q on two adjacent rings. ⁴ To Q ⁸ Bound to C ₁ -C ₆ -Forming an aliphatic, aromatic or heteroaromatic ring which may be mono- or polysubstituted by alkyl, or halogen, in which case m is 2,
m is preferably 0, 1, 2, 3;
X is preferably hydroxyl, cyano or C ₁ -C ₄ C may be further mono- to tri-substituted by alkoxy ₁ -C ₄ -Haloalkyl or C ₃ -C ₅ -Halocycloalkyl,
W is preferably O or S;
AY together are preferably cyano, or pyrrolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, pyrazolyl, imidazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl, 1, 2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,3,4-oxadiazolyl, 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,3,4-thiadiazolyl, tetrazolyl, pyridyl, Pyrimidinyl, pyridazinyl, pyrazinyl, 1,2,4-triazinyl, 1,3,5-triazinyl, pyrrolidinyl, isoxazolidinyl, pyrazolidinyl, oxazolidinyl, thiazolidinyl, imidazolinyl, imidazolidinyl, 1,2,4-oxadiazolidinyl 1,2,4-thiadi Zolidinyl, 1,2,4-triazolidinyl, 1,3,4-oxadiazolidinyl, 1,3,4-thiadiazolidinyl, 1,3,4-triazolidinyl, pyrrolinyl, isoxazolinyl, 2,3 -Dihydropyrazolyl, 3,4-dihydropyrazolyl, 4,5-dihydropyrazolyl, 2,3-dihydrooxazolyl, 3,4-dihydrooxazolyl, piperidinyl, oxopyrrolidinyl, 3-oxo-1,2 , 4-triazolidinyl, 5-oxo-1,2,4-triazolidinyl, dioxopyrrolidinyl, oxomorpholinyl, oxopiperidinyl and oxopiperazinyl A good heterocycle or oxoheterocycle,
Here, the substituent may be mono-substituted from halogen, nitro, cyano, amino, or hydroxyl, or may be mono-substituted or the same or different, and may be poly-substituted amino, C ₁ -C ₆ -Alkyl, C ₁ -C ₆ -Alkoxy, C ₁ -C ₆ -Alkoxy-C ₁ -C ₆ -Alkyl, C ₁ -C ₆ -Alkylcarbonyl, C ₂ -C ₆ -Alkenyl, C ₂ -C ₆ -Alkynyl, C ₃ -C ₆ -Cycloalkyl, aryl, hetaryl, C ₁ -C ₆ -Arylalkyl, C ₁ -C ₆ -Hetarylalkyl, aryloxy, hetaryloxy, C ₁ -C ₆ -Alkylthio, C ₁ -C ₆ -Alkylsulfinyl, C ₁ -C ₆ -Alkylsulfonyl, C ₁ -C ₆ -Alkoxycarbonyl and C ₁ -C ₆ -Selected from alkylaminocarbonyl,
Here, the substituents are independently halogen, nitro, cyano, C ₁ -C ₆ -Alkyl, C ₁ -C ₆ -Haloalkyl, C ₁ -C ₆ -Alkoxy, C ₁ -C ₆ -Haloalkoxy, C ₃ -C ₆ -Cycloalkyl, C ₃ -C ₆ -Cycloalkylcarbonyl, C ₁ -C ₆ -Alkylthio, C ₁ -C ₆ -Alkylsulfinyl, C ₁ -C ₆ -Alkylsulfonyl, (C ₁ -C ₆ -Alkoxy) carbonyl, C ₂ -C ₆ -Alkenyl, C ₂ -C ₆ -Alkynyl, C ₁ -C ₆ -Alkylamino, C ₃ -C ₆ -Cycloalkylamino, (C ₁ -C ₆ -Alkyl) C ₃ -C ₆ -Cycloalkylamino or di (C ₁ -C ₄ ) Selected from alkylamino,
Or
A is preferably a moiety —NR ¹³ C (= O)-, -NR ¹³ C (= S)-, -C (R ¹¹ ) (R ¹² ) NR ¹³ C (= O)-, -C (R ¹¹ ) (U) NR ¹³ C (= O)-, -C (R ¹¹ ) (R ¹² ) NR ¹³ C (= S)-, -C (= O) NR ¹³ -, -C (= O) N (R ¹³ ) -O-, -C (= O) NR ¹³ CH ₂ -, -C (= S) NR ¹³ -, -C (= S) NR ¹³ CH ₂ -, -C (= O) NR ¹³ CH = N-O-, -C (R ¹¹ ) = N—O—, —C (NH ₂ ) = N—O—, —C (R ¹¹ ) = N-OCH ₂ C (= O) NR ¹³ -, -C (R ¹¹ ) (R ¹² ) NR ¹³ C (= O) NR ¹⁴ -, -C (R ¹¹ ) (R ¹² ) NR ¹³ C (= O) CH ₂ S-, -NR ¹³ (C = O) NR ¹⁴ -, -C (= O)-, -C (= N-O-R ¹³ )-, -C (= O) O-, -C (= O) OCH ₂ C (= O) NR ¹³ -, -C (= O) OCH ₂ C (= O) NH-, -C (= O) NR ¹³ CH ₂ C (= O) NR ¹⁴ -, -C (= O) NR ¹³ CH ₂ C (= O)-, -C (= O) NR ¹³ CH ₂ C (= O) O-, -C (= O) NR ¹³ NR ¹⁴ C (= O)-, -C (= O) NR ¹³ NR ¹⁴ -, -N (R ¹³ )-, -C (R ¹¹ ) (R ¹² ) NR ¹³ -, -S (= O) _p -, -S (= O) ₂ NR ¹³ -, -NR ¹³ S (= O) ₂ -, -C (R ¹¹ ) (R ¹² ) NR ¹³ S (= O) ₂ -, -C (= O) CH (CN)-or -CH (CN) NR ¹³ A divalent chemical moiety selected from-wherein the first (left) linking site in said divalent chemical moiety is at position Q ⁴ To Q ⁸ The second (right-hand) linking moiety is linked to Y in any of the rings, where
p may preferably take a value of 0, 1 or 2, where
U is preferably at position Q ⁴ To Q ⁸ And optionally substituted C forming a 5- to 6-membered ring with the carbon atom adjacent to the linking site of A on the ring ₂ -C ₄ -Alkyl,
Here, each of the substituents is independently halogen, C ₁ -C ₃ -Alkyl and C ₁ -C ₃ -Selected from alkoxy
R ¹¹ And R ¹² Are preferably each independently hydrogen, cyano, or monosubstituted or trisubstituted with the same or different ₁ -C ₄ -Alkyl or C ₃ -C ₆ -Cycloalkyl,
Here, the substituents are independently halogen, cyano, nitro, hydroxyl, C ₁ -C ₆ -Alkyl or C ₁ -C ₆ -Selected from alkoxy
Or
R ¹¹ And R ¹² Together form a 3- to 6-membered ring which may contain 1 to 2 double bonds ₂ -C ₅ -Alkyl or C ₃ -C ₅ -Alkenyl,
Or
R ¹¹ And R ¹³ Together form a 3 to 7 membered ring which may contain 1 to 2 double bonds ₂ -C ₅ -Alkyl or C ₃ -C ₅ -Alkenyl,
R ¹³ And R ¹⁴ Are preferably each independently hydrogen, monosubstituted, or polysubstituted with the same or different ₁ -C ₄ -Alkyl or C ₃ -C ₆ -Cycloalkyl, C ₁ -C ₄ -Alkylcarbonyl, C ₁ -C ₄ -Alkoxycarbonyl or aryloxycarbonyl,
Here, the substituents are independently halogen, cyano, nitro, hydroxyl, C ₁ -C ₄ -Alkyl and C ₁ -C ₄ -Selected from alkoxy
Or
R ¹³ And R ¹⁴ Together form a 3 to 7 membered ring which may contain 1 to 2 double bonds ₂ -C ₅ -Alkyl or C ₃ -C ₅ -Alkenyl,
Y may preferably be hydrogen or monosubstituted or C which may be polysubstituted with the same or different ₁ -C ₆ -Alkyl, C ₂ -C ₆ -Alkenyl, C ₂ -C ₆ -Alkynyl, C ₃ -C ₆ -Cycloalkyl, C ₃ -C ₆ -Cycloalkenyl, which may be mono-substituted or phenyl which may be the same or different and poly-substituted, or thienyl, furanyl, pyrrolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, pyrazolyl, imidazolyl 1,2,3-triazolyl, 1,2,4-triazolyl, 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,3,4-oxadiazolyl, 1,2,3-thiadiazolyl, 1 , 2,4-thiadiazolyl, 1,3,4-thiadiazolyl, tetrazolyl, pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, 1,2,4-triazinyl, 1,3,5-triazinyl, pyrrolidinyl, isoxazolidinyl, pyrazolidinyl , Oxazolidinyl, thiazoly Nyl, imidazolidinyl, 1,2,4-oxadiazolidinyl, 1,2,4-thiadiazolidinyl, 1,2,4-triazolidinyl, 1,3,4-oxadiazolidinyl, 1,3,4 -Thiadiazolidinyl, 1,3,4-triazolidinyl, pyrrolinyl, isoxazolinyl, 2,3-dihydropyrazolyl, 3,4-dihydropyrazolyl, 4,5-dihydropyrazolyl, 2,3-dihydrooxazolyl 3,4-dihydrooxazolyl, piperidinyl, tetrahydrothienyl, piperazinyl, morpholinyl, thiomorpholinyl, dihydropyranyl, tetrahydropyranyl, tetrahydrothienyl, 1,4-dioxanyl, 1,3-dioxanyl, dioxolanyl, dioxolyl, tetrahydrofuranyl , Dihydrofuranyl, oxetanyl, Ethanyl, oxidothietanyl, dioxide thietanyl, oxiranyl, azetidinyl, oxoazetidinyl, oxaziridinyl, oxazepanyl, oxadinanyl, azepanyl, oxopyrrolidinyl, dioxopyrrolidinyl, oxomorpholinyl, oxopiperidinyl, oxo A mono- or poly-substituted heterocycle from the group of piperazinyl or oxotetrahydrofuranyl,
Here, the substituent may be mono-substituted from halogen, nitro, cyano, or hydroxyl, or may be poly-substituted with the same or different amino, C ₁ -C ₆ -Alkyl, C ₁ -C ₆ -Alkoxy, C ₁ -C ₆ -Alkoxy-C ₁ -C ₆ -Alkyl, C ₁ -C ₆ -Alkylcarbonyl, C ₂ -C ₆ -Alkenyl, C ₂ -C ₆ -Alkynyl, C ₃ -C ₆ -Cycloalkyl, aryl, hetaryl, C ₁ -C ₆ -Arylalkyl, C ₁ -C ₆ -Hetarylalkyl, aryloxy, hetaryloxy, C ₁ -C ₆ -Alkylthio, C ₁ -C ₆ -Alkylsulfinyl, C ₁ -C ₆ -Alkylsulfonyl, C ₁ -C ₆ -Selected from alkoxycarbonyl or heterocycle;
Here, the substituent is independently halogen, nitro, hydroxyl, amino, cyano, C ₁ -C ₆ -Alkyl, C ₁ -C ₆ -Alkylcarbonyl, C ₁ -C ₆ -Haloalkyl, C ₁ -C ₆ -Alkoxy, C ₁ -C ₆ -Haloalkoxy, C ₃ -C ₆ -Cycloalkyl, C ₃ -C ₆ -Cycloalkylcarbonyl, C ₁ -C ₆ -Alkylthio, C ₁ -C ₆ -Alkylsulfinyl, C ₁ -C ₆ -Alkylsulfonyl, (C ₁ -C ₆ -Alkoxy) carbonyl, C ₂ -C ₆ -Alkenyl, C ₂ -C ₆ -Alkynyl, C ₁ -C ₆ -Alkylamino, C ₃ -C ₆ -Cycloalkylamino, (C ₁ -C ₆ -Alkyl) C ₃ -C ₆ -Cycloalkylamino, di (C ₁ -C ₄ ) Alkylamino or C ₁ -C ₆ -May be selected from alkylaminocarbonyl,
Q ¹ To Q ³ Are preferably independently of each other hydrogen or R ¹ A carbon atom substituted by or N and Q ¹ To Q ³ The number of nitrogen atoms in is 2 or less,
Q ⁴ Is preferably hydrogen or R ⁶ Or a carbon atom bonded to V (where V is R ⁴ Or N), and
Q ⁵ To Q ⁸ Are preferably each independently hydrogen, R ⁶ Or a carbon atom substituted by AY, or N and Q ⁴ To Q ⁸ In which the number of nitrogen atoms is 2 or less, and Q ⁵ , Q ⁶ , Q ⁷ , Q ⁸ Exactly one of them is replaced by AY;
R ¹ Are more preferably hydrogen, halogen, nitro, cyano, monosubstituted, or polysubstituted with the same or different ₁ -C ₄ -Alkyl, C ₁ -C ₄ -Alkoxy, C ₁ -C ₄ -Alkylthio, C ₁ -C ₄ -Alkylsulfinyl, C ₁ -C ₄ -Alkylsulfonyl, C ₁ -C ₄ -Alkylcarbonyl, C ₁ -C ₄ -Alkoxycarbonyl, C ₁ -C ₄ -Alkylaminocarbonyl, C ₁ -C ₄ -Dialkylaminocarbonyl or C ₁ -C ₄ -Alkylaminosulfonyl,
Here, the substituents are independently halogen, cyano, nitro, hydroxyl, C ₁ -C ₄ -Alkyl, C ₁ -C ₄ -Alkoxy, C ₃ -C ₄ -Cycloalkyl, C ₁ -C ₄ -Haloalkoxy or C ₁ -C ₄ -Selected from alkylthio;
n is more preferably 1, 2 or 3,
R ² Is more preferably hydrogen, cyano, hydroxyl, mono-substituted or the same or different from tri-substituted C ₁ -C ₄ -Alkyl or C ₁ -C ₄ -Alkoxy,
Here, the substituent is independently halogen, cyano, nitro, hydroxyl, amino, C ₁ -C ₄ -Alkyl and C ₁ -C ₄ -Selected from alkoxy
R ³ Is more preferably hydrogen, monosubstituted, or polysubstituted with the same or different ₁ -C ₄ -Alkyl, C ₂ -C ₄ -Alkenyl, C ₂ -C ₄ -Alkynyl, C ₁ -C ₄ -Alkylcarbonyl, C ₁ -C ₄ -Alkylsulfonyl, C ₁ -C ₄ -Alkoxycarbonyl or aryloxycarbonyl,
Here, the substituents are independently halogen, cyano, nitro, hydroxyl, C ₁ -C ₆ -Alkyl, C ₁ -C ₆ -Alkoxy or C ₁ -C ₄ -Selected from alkoxycarbonyl;
V is more preferably R ⁴ Or Q through a single bond ⁴ -O-, S and -N (R ⁸ )-Is a divalent chemical moiety selected from
R ⁴ Is more preferably hydrogen or mono-substituted or tri-substituted with the same or different ₁ -C ₄ -Alkyl, wherein the substituents are each independently halogen, C ₁ -C ₄ -Alkyl and C ₁ -C ₄ -Selected from alkoxy
R ⁸ Are more preferably hydrogen, cyano, hydroxyl, monosubstituted, or polysubstituted with the same or different ₁ -C ₄ -Alkyl, C ₂ -C ₄ -Alkenyl, C ₃ -C ₄ -Alkynyl, aryl-C ₁ -C ₄ -Alkyl, C ₁ -C ₄ -Alkoxy, C ₁ -C ₆ -Alkoxycarbonyl or C ₁ -C ₄ -Alkylcarbonyl;
Here, the substituents are independently halogen, cyano, nitro, hydroxyl, C ₁ -C ₆ -Alkyl, C ₁ -C ₆ -Alkoxy, C ₁ -C ₄ -Alkoxycarbonyl, aminocarbonyl, C ₁ -C ₄ -Alkylaminocarbonyl, C ₁ -C ₄ -Dialkylaminocarbonyl or aryl-C ₁ -C ₄ -Selected from alkoxy
R ⁵ Is more preferably hydrogen or mono-substituted or tri-substituted with the same or different ₁ -C ₄ -Alkyl, wherein the substituents are each independently halogen, C ₁ -C ₄ -Alkyl or C ₁ -C ₄ -Selected from alkoxy
R ⁶ Are more preferably hydrogen, halogen, nitro, cyano, monosubstituted, or polysubstituted with the same or different ₁ -C ₄ -Alkyl, C ₂ -C ₄ -Alkynyl, C ₁ -C ₄ -Alkoxy, (C ₁ -C ₄ -Alkyl) carbonyl, (C ₁ -C ₄ -Alkylamino) carbonyl, (C ₁ -C ₄ -Dialkylamino) carbonyl, C ₁ -C ₄ -Alkylthio, C ₁ -C ₄ -Alkylsulfinyl, C ₁ -C ₄ -Alkylsulfonyl, C ₁ -C ₄ -Alkylaminosulfonyl or C ₁ -C ₄ -Alkylsulfonylamino,
Here, each of the substituents is independently halogen, cyano, nitro, C ₁ -C ₆ -Alkyl, C ₁ -C ₆ -Alkoxy, C ₁ -C ₆ -Haloalkoxy and C ₁ -C ₆ -Selected from alkylthio;
Or
R ⁶ More preferably -OCH ₂ O-, -OCF ₂ O-, -OCH ₂ CH ₂ O-, -OCF ₂ CF ₂ O— or —CH═CH—CH═CH—, wherein the substituent is Q in each case ⁴ To Q ⁸ Forming a ring through two adjacent groups selected from
m is more preferably 0, 1, 2, 3;
X is more preferably C ₁ -C ₄ -Haloalkyl or C ₃ -C ₅ -Halocycloalkyl, which is hydroxyl, cyano or C ₁ -C ₄ May be further mono- to tri-substituted by alkoxy,
W is more preferably O,
AY together is more preferably cyano or may be mono- or polysubstituted pyrrolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, pyrazolyl, imidazolyl, 2-imidazolinyl, 1,2,3 -Triazolyl, 1,2,4-triazolyl, 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,3,4-oxadiazolyl, 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl 1,3,4-thiadiazolyl, tetrazolyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, 1,2,4-triazinyl and a heterocyclic ring from the group of 1,3,5-triazinyl,
Here, the substituent is a halogen, nitro, cyano, hydroxyl, which may be mono-substituted or the same or different, and may be poly-substituted amino, C ₁ -C ₄ -Alkyl, C ₁ -C ₄ -Alkoxy, C ₁ -C ₄ -Alkoxy-C ₁ -C ₄ -Alkyl, C ₂ -C ₄ -Alkynyl, C ₁ -C ₆ -Alkylthio, C ₁ -C ₆ -Alkylsulfinyl, C ₁ -C ₆ -Alkylsulfonyl, C ₃ -C ₆ -Selected from cycloalkyl, aryl and hetaryl;
Here, the substituent is independently halogen, hydroxyl, amino, nitro, cyano, C ₁ -C ₆ -Alkyl, C ₁ -C ₆ -Haloalkyl, C ₁ -C ₆ -Alkoxy, C ₁ -C ₆ -Haloalkoxy, C ₃ -C ₆ -Cycloalkyl, C ₃ -C ₆ -Cycloalkylcarbonyl, C ₁ -C ₆ -Alkylthio, C ₁ -C ₆ -Alkylsulfinyl, C ₁ -C ₆ -Alkylsulfonyl, (C ₁ -C ₆ -Alkoxy) carbonyl, C ₂ -C ₆ -Alkenyl, C ₂ -C ₆ -Alkynyl, C ₁ -C ₆ -Alkylamino, C ₃ -C ₆ -Cycloalkylamino, (C ₁ -C ₆ -Alkyl) C ₃ -C ₆ -Cycloalkylamino, di (C ₁ -C ₄ ) Alkylamino or C ₁ -C ₆ -Selected from alkylaminocarbonyl,
A is more preferably a moiety —NR ¹³ C (= O)-, -C (R ¹¹ ) (R ¹² ) NR ¹³ C (= O)-, -C (= O) O-, -C (R ¹¹ ) (U) NR ¹³ C (= O)-, -C (R ¹¹ ) (R ¹² ) N (U) C (= O)-, -C (= O) NR ¹³ -, -C (= O) N (R ¹³ ) -O-, -C (= O) NR ¹³ CH ₂ -, -C (= O) NR ¹³ CH = N-O-, -C (R ¹¹ ) = N—O—, —C (R ¹¹ ) = N-OCH ₂ C (= O) NR ¹³ -, -C (R ¹¹ ) (R ¹² ) NR ¹³ C (= O) NR ¹⁴ -, -C (R ¹¹ ) (R ¹² ) NR ¹³ C (= O) CH ₂ S-, -NR ¹³ (C = O) NR ¹⁴ -, -C (= O)-, -C (= N-O-R ¹³ )-, -C (= O) NR ¹³ CH ₂ C (= O) NR ¹⁴ -, -C (= O) NR ¹³ CH ₂ C (= O)-, -C (= O) NR ¹³ CH ₂ C (= O) O-, -C (= O) NR ¹³ NR ¹⁴ C (= O)-, -C (= O) NR ¹³ NR ¹⁴ -, -N (R ¹³ )-, -C (R ¹¹ ) (R ¹² ) NR ¹³ -, -S (= O) _p -, -S (= O) ₂ NR ¹³ -, -NR ¹³ S (= O) ₂ -, -C (R ¹¹ ) (R ¹² ) NR ¹³ S (= O) ₂ -, C (= O) CH (CN)-or -CH (CN) NR ¹³ A divalent chemical moiety selected from-wherein the first (left) linking site in the divalent chemical moiety is at position Q ⁴ To Q ⁸ And the second (right) linking site is linked to Y, where
p may more preferably take a value of 0, 1 or 2, and where
U is more preferably position Q ⁴ To Q ⁸ And optionally substituted C, which forms a 5- to 6-membered ring with A on the ring and the carbon atom adjacent to the linking site. ₂ -C ₄ -Alkyl,
Here, each of the substituents is independently C ₁ -C ₃ -Selected from alkyl and halogen, and wherein
R ¹¹ And R ¹² More preferably, each independently hydrogen, C ₁ -C ₄ -Alkyl or C ₁ -C ₄ -Haloalkyl,
Or
R ¹¹ And R ¹² Together form a 3- to 6-membered ring which may contain 1 to 2 double bonds ₂ -C ₅ -Alkyl or C ₃ -C ₅ -Alkenyl,
Or
R ¹¹ And R ¹³ Together form a 3 to 7 membered ring which may contain 1 to 2 double bonds ₂ -C ₅ -Alkyl or C ₃ -C ₅ -Alkenyl, and where
R ¹³ And R ¹⁴ More preferably, each may be independently hydrogen, mono-substituted, or poly-substituted with the same or different ones. ₁ -C ₄ -Alkyl or C ₃ -C ₆ -Cycloalkyl, C ₁ -C ₄ -Alkylcarbonyl, aryloxycarbonyl or C ₁ -C ₄ -Alkoxycarbonyl,
Here, the substituent is independently halogen, cyano, C ₁ -C ₄ -Alkyl and C ₁ -C ₄ -Selected from alkoxy
Or
R ¹³ And R ¹⁴ Together form a 3 to 7 membered ring which may contain 1 to 2 double bonds ₂ -C ₅ -Alkyl or C ₃ -C ₅ -Alkenyl,
Y is more preferably hydrogen or mono-substituted, or C may be poly-substituted with the same or different ₁ -C ₆ -Alkyl, C ₂ -C ₆ -Alkenyl, C ₂ -C ₆ -Alkynyl, C ₃ -C ₆ -Cycloalkyl, C ₃ -C ₆ -Cycloalkenyl, which may be monosubstituted or phenyl which may be the same or different and polysubstituted, or thienyl, furanyl, pyrrolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, pyrazolyl, Imidazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl, 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,3,4-oxadiazolyl, 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,3,4-thiadiazolyl, tetrazolyl, pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, 1,2,4-triazinyl, 1,3,5-triazinyl, piperazinyl, morpholinyl, tetrahydropyranyl, 1,4-dioxanyl, 1, -Dioxanyl, dioxolanyl, dioxolyl, tetrahydrofuranyl, dihydrofuranyl, oxetanyl, thietanyl, oxidothietanyl, dioxide thietanyl, oxiranyl, azetidinyl, oxoazetidinyl, oxazepanyl, oxadinanyl, azepanyl, oxopyrrolidinyl, dioxopyrrole A mono- or poly-substituted heterocycle from the group of dinyl, oxomorpholinyl, oxopiperidinyl, oxopiperazinyl and oxotetrahydrofuranyl,
Here, the substituent may be mono-substituted from halogen, nitro, cyano, or hydroxyl, or may be poly-substituted with the same or different amino, C ₁ -C ₆ -Alkyl, C ₁ -C ₆ -Alkoxy, C ₁ -C ₆ -Alkoxy-C ₁ -C ₆ -Alkyl, C ₁ -C ₆ -Alkylcarbonyl, C ₂ -C ₆ -Alkenyl, C ₂ -C ₆ -Alkynyl, C ₃ -C ₆ -Cycloalkyl, aryl, hetaryl, C ₁ -C ₆ -Arylalkyl, C ₁ -C ₆ -Hetarylalkyl, aryloxy, hetaryloxy, C ₁ -C ₆ -Alkylsulfinyl, C ₁ -C ₆ -Alkylsulfonyl, C ₁ -C ₆ -Alkylthio, C ₁ -C ₆ -Selected from alkoxycarbonyl and heterocycle;
Here, the substituent is independently halogen, nitro, hydroxyl, amino, cyano, C ₁ -C ₆ -Alkyl, C ₁ -C ₆ -Alkylcarbonyl, C ₁ -C ₆ -Haloalkyl, C ₁ -C ₆ -Alkoxy, C ₁ -C ₆ -Haloalkoxy, C ₃ -C ₆ -Cycloalkyl, C ₃ -C ₆ -Cycloalkylcarbonyl, C ₁ -C ₆ -Alkylthio, C ₁ -C ₆ -Alkylsulfinyl, C ₁ -C ₆ -Alkylsulfonyl, (C ₁ -C ₆ -Alkoxy) carbonyl, C ₂ -C ₆ -Alkenyl, C ₂ -C ₆ -Alkynyl, C ₁ -C ₆ -Alkylamino, C ₃ -C ₆ -Cycloalkylamino, (C ₁ -C ₆ -Alkyl) C ₃ -C ₆ -Cycloalkylamino, di (C ₁ -C ₄ ) Alkylamino and C ₁ -C ₆ -Can be selected from alkylaminocarbonyl,
Q ¹ To Q ³ More preferably each independently hydrogen or R ¹ A carbon atom substituted by or N, wherein Q ¹ To Q ³ The number of nitrogen atoms in is 1 or less,
Q ⁴ More preferably hydrogen or R ⁶ Carbon atoms substituted by or bonded to V (where V is R ⁴ Or N), and
Q ⁵ To Q ⁸ More preferably each independently hydrogen, R ⁶ Or a carbon atom substituted by AY, or N, where Q ⁴ To Q ⁸ The number of nitrogen atoms in is 1 or less, and Q ⁵ , Q ⁶ , Q ⁷ , Q ⁸ Exactly one of the is replaced by AY;
R ¹ Are most preferably hydrogen, nitro, cyano, fluorine, chlorine, bromine, iodine, methyl, ethyl, n- or i-propyl, fluoromethyl, chloromethyl, trichloromethyl, difluoromethyl, dichlorofluoromethyl, chlorodifluoromethyl, Trifluoromethyl, fluoroethyl, chloroethyl, difluoroethyl, dichloroethyl, trifluoroethyl, chlorofluoroethyl, chlorodifluoroethyl, dichlorofluoroethyl, tetrafluoroethyl, pentafluoroethyl, chlorotetrafluoroethyl, trichloroethyl, heptafluoro- n-propyl, heptafluoroisopropyl, methoxy, ethoxy, n- or i-propoxy, fluoromethoxy, difluoromethoxy, trifluoromethoxy, methylthio, ethyl Thio, difluoromethylthio, trifluoromethylthio, chlorodifluoromethylthio, methylsulfinyl, trifluoromethylsulfinyl, trifluoromethylsulfonyl, methylsulfonyl, ethylsulfonyl, acetyl, propionyl, methoxycarbonyl, ethoxycarbonyl, methylaminocarbonyl, dimethylaminocarbonyl or Ethylaminocarbonyl,
n is most preferably 1, 2 or 3;
R ² Is most preferably hydrogen, methyl or ethyl,
R ³ Are most preferably hydrogen, methyl, ethyl, 2-ethynyl, 2-propenyl, methoxymethyl, ethoxymethyl, methylcarbonyl, ethylcarbonyl, methoxycarbonyl, ethoxycarbonyl, n-propoxycarbonyl, i-propoxycarbonyl, n-butoxy Carbonyl, t-butoxycarbonyl or phenoxycarbonyl,
V is most preferably R ⁴ Or —O— or —N (R ⁸ )-And Q through a single bond ⁴ And here
R ⁴ Is most preferably hydrogen or methyl, and
R ⁸ Are most preferably hydrogen, methyl, ethyl, methylcarbonyl, ethylcarbonyl, methoxymethyl, ethoxymethyl, cyanomethyl, cyanoeth-2-yl, propyl, phenylmethyl, prop-2-en-1-yl, prop-2- In-1-yl, benzyloxy, methoxycarbonyl, ethoxycarbonyl, methoxycarbonylmethyl, ethoxycarbonylmethyl, methoxycarbonyleth-2-yl, ethoxycarbonyleth-2-yl, amidomethyl, amidoethyl or amidoprop-3-yl ,
R ⁵ Is most preferably hydrogen,
R ⁶ Are most preferably hydrogen, nitro, cyano, fluorine, chlorine, bromine, iodine, methyl, ethyl, n- or i-propyl, n-, i-, s- or t-butyl, ethynyl, propynyl, fluoromethyl, Chloromethyl, trichloromethyl, difluoromethyl, dichlorofluoromethyl, chlorodifluoromethyl, trifluoromethyl, fluoroethyl, chloroethyl, difluoroethyl, dichloroethyl, trifluoroethyl, chlorofluoroethyl, chlorodifluoroethyl, fluorodichloroethyl, tetrafluoro Ethyl, pentafluoroethyl, chlorotetrafluoroethyl, trichloroethyl, heptafluoro-n-propyl, heptafluoroisopropyl, methoxy, ethoxy, n- or i-propoxy, fluoromethoxy, di Fluoromethoxy, trifluoromethoxy, methylthio, ethylthio, difluoromethylthio, trifluoromethylthio, chlorodifluoromethylthio, methylsulfinyl, trifluoromethylsulfinyl, trifluoromethylsulfonyl, methylsulfonyl, ethylsulfonyl, acetyl, propionyl, methoxycarbonyl, ethoxycarbonyl, Methylaminocarbonyl, ethylaminocarbonyl or dimethylaminocarbonyl,
m is most preferably 0, 1 or 2;
X is most preferably trifluoromethyl, difluoromethyl, fluoromethyl, chlorodifluoromethyl, dichlorofluoromethyl, 2-fluoroethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, 1,2, 2,2-tetrafluoroethyl, 1-chloro-1,2,2,2-tetrafluoroethyl, 2-chloro-2,2-difluoroethyl, 1,1-difluoroethyl, pentafluoroethyl, heptafluoro-n -Propyl or nonafluoro-n-butyl,
W is most preferably O,
AY together are most preferably cyano or may be mono- or polysubstituted 1,2,4-oxadiazol-3-yl, 1H-imidazol-1-yl 1H-pyrazol-1-yl, 1H-1,2,4-triazol-1-yl, 1H-1,2,3-triazol-1-yl, 1H-1,3,4-triazol-1-yl A heterocycle from the group of 1H-1,2,3,4-tetrazol-1-yl or 2H-1,2,3,4-tetrazol-1-yl;
Here, the substituent is fluorine, chlorine, cyano, hydroxyl, amino, methyl, ethyl, difluoromethyl, trifluoromethyl, pentafluoroethyl, n- or i-propyl, cyclopropyl, methoxy, ethoxy, n- or i-propoxy, fluoromethoxy, difluoromethoxy, trifluoromethoxy, fluoroethoxy, difluoroethoxy, trifluoroethoxy, methylthio, methylsulfinyl, methylsulfonyl, ethylthio, ethylsulfinyl, ethylsulfonyl, methoxycarbonyl, ethoxycarbonyl, methylaminocarbonyl or Selected from dimethylaminocarbonyl,
Or
A is most preferably a moiety —NR ¹³ C (= O)-, -C (R ¹¹ ) (R ¹² ) NR ¹³ C (= O)-, -C (R ¹¹ ) (R ¹² ) NR ¹³ S (= O) ₂ -, -C (= O) NR ¹³ -, -C (= O) N (R ¹³ ) -O-, -C (= O) NR ¹³ CH ₂ -, -S (= O) _p -, -S (= O) ₂ NR ¹³ -, -C (= O) O-, -C (= O) NR ¹³ CH ₂ C (= O) NR ¹⁴ -, -C (R ¹¹ ) (R ¹² ) NR ¹³ -, C (R ¹¹ ) (U) NR ¹³ C (= O)-and -C (= O) NR ¹³ NR ¹⁴ A divalent chemical moiety selected from: wherein the first (left) linking site in said divalent chemical moiety is at position Q ⁴ To Q ⁸ A second (right side) linking site is linked to Y in one of the rings,
U is most preferably ethyl or n-propyl, and position Q ⁴ To Q ⁸ A 5-membered ring or a 6-membered ring together with the carbon atom adjacent to the linking site of A to the ring in
p is most preferably 0, 1, 2 and
R ¹¹ And R ¹² Are most preferably hydrogen or methyl respectively.
R ¹³ And R ¹⁴ Are most preferably hydrogen, methyl, ethyl, cyclopropyl, cyanoethyl, 2-ethynyl, 2-propenyl, methoxymethyl, ethoxymethyl, methylcarbonyl, ethylcarbonyl, n-propylcarbonyl, i-propylcarbonyl, n- Butylcarbonyl, t-butylcarbonyl, methoxycarbonyl, ethoxycarbonyl, n-propoxycarbonyl, i-propoxycarbonyl, n-butoxycarbonyl, t-butoxycarbonyl or phenoxycarbonyl,
Y is most preferably hydrogen or mono-substituted, or may be poly-substituted with the same or different, methyl, ethyl, n- or i-propyl, n-, i-, s- or t-butyl, n-, i-, s-, t- or neo-pentyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, ethenyl, propenyl, butenyl, pentenyl, ethynyl, propynyl, butynyl or pentynyl;
Wherein no more than 5 substituents may be selected from fluorine and chlorine and no more than 2 substituents may be bromine, cyano, nitro, hydroxyl, amino, methylamino, dimethylamino, cyclopropyl, trifluoromethyl, Methoxy, ethoxy, n- or i-propoxy, fluoromethoxy, difluoromethoxy, trifluoromethoxy, fluoroethoxy, difluoroethoxy, trifluoroethoxymethylthio, methylsulfinyl, methylsulfonyl, ethylthio, ethylsulfinyl, ethylsulfonyl, methoxycarbonyl and ethoxy May be selected from carbonyl,
One substituent may be mono- to tri-substituted phenyl, pyridin-2-yl, pyridin-3-ylpyridin-4-yl, thiazol-2-yl, thiazol-4-yl, furan- May be selected from 2-yl, pyrazol-1-yl, pyrazol-5-yl and pyrazol-3-yl, wherein the substituent is fluorine, chlorine, bromine, cyano, nitro, hydroxyl, methyl, Ethyl, n- or i-propyl, amino, methylamino, dimethylamino, cyclopropyl, methoxy, ethoxy, n- or i-propoxy, fluoromethoxy, difluoromethoxy, trifluoromethoxy, fluoroethoxy, difluoroethoxy, trifluoroethoxy , Methylthio, methylsulfinyl, methylsulfonyl, ethylthio It may be selected from ethylsulfinyl or ethylsulfonyl,
Or
Mono-trisubstituted oxetane-3-yl, thietan-3-yl, 1-oxidethietan-3-yl, 1,1-dioxidethietan-3-yl, tetrahydrofuran-2-yl, Tetrahydrofuran-3-yl, tetrahydropyran-2-yl, tetrahydropyran-3-yl, tetrahydropyran-4-yl, 1,3-dioxan-2-yl, 1,3-dioxan-3-yl, 1,3 -Dioxane-4-yl, 1,4-dioxane-2-yl, morpholin-1-yl, phenyl, pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, pyrimidin-2-yl, pyrimidine -4-yl, pyrimidin-5-yl, pyridazin-3-yl, pyrazin-2-yl, furan-2-yl, furan-3-yl, thiophen-2- Thiophen-3-yl, pyrrol-2-yl, thiazol-2-yl, thiazol-4-yl, thiazol-5-yl, 1,2,4-thiadiazol-5-yl, oxazol-2-yl, Oxazol-4-yl, oxazol-5-yl, isoxazol-3-yl, isoxazol-4-yl, isoxazol-5-yl, 1,2,3-oxadiazol-4-yl, 1,3 , 4-oxadiazol-2-yl, 1H-imidazol-2-yl, 1H-imidazol-4-yl, 1H-imidazol-5-yl, 1H-pyrazol-3-yl, 1H-pyrazol-4-yl 1H-pyrazol-5-yl, 1H-1,2,4-triazol-3-yl, 1H-1,2,4-triazol-5-yl, 1H-1,2,3-to Azol-4-yl, 1H-1,2,3-triazol-5-yl, 2H-1,2,3-triazol-2-yl, 2H-1,2,3-triazol-4-yl, 1H- 1,3,4-triazol-2-yl, 1H-1,2,3,4-tetrazol-5-yl, 2-oxopiperidin-3-yl, 2-oxotetrahydrofuran-3-yl or 5-oxotetrahydrofuran -2-yl,
Here, the substituent is fluorine, chlorine, bromine, cyano, nitro, hydroxyl, amino, methyl, ethyl, difluoromethyl, trifluoromethyl, pentafluoroethyl, n- or i-propyl, cyclopropyl, methoxy, ethoxy. N- or i-propoxy, fluoromethoxy, difluoromethoxy, trifluoromethoxy, fluoroethoxy, difluoroethoxy, trifluoroethoxy, methylthio, methylsulfinyl, methylsulfonyl, ethylthio, ethylsulfinyl, ethylsulfonyl, methoxycarbonyl, ethoxycarbonyl, May be selected from methylaminocarbonyl and dimethylaminocarbonyl,
Q ¹ To Q ³ Most preferably, each independently by hydrogen or R ¹ A carbon atom substituted by or N and Q ¹ To Q ³ The number of nitrogen atoms in is 1 or less,
Q ⁴ Most preferably, hydrogen or R ⁶ Or a carbon atom bonded to V (where V is R ⁴ Other than
Q ⁵ To Q ⁸ Most preferably, each independently hydrogen, R ⁶ Or a carbon atom substituted by AY, or N, where Q ⁵ To Q ⁸ The number of nitrogen atoms in is 1 or less, Q ⁵ , Q ⁶ , Q ⁷ , Q ⁸ It is believed that exactly one of these is replaced by AY.

The individual specific, preferred, more preferred and most preferred definitions given above for substituents R ¹ to R ⁶ , X, W, A, Y and Q ¹ to Q ⁸ are according to the invention. They can be combined with each other as desired.

  Preferred compounds of the present invention are novel compounds of the following formulas (IA) to (ID).

式中、
（Ｒ^１）_ｎ、Ｒ^３、Ｒ^８、（Ｒ^６）_ｍ、Ｘ、ＡおよびＹ（すなわち、Ａ、ＹおよびＡ−Ｙ）は、上記の一般的な、好ましい、より好ましいおよび最も好ましい定義を表す。

Where
(R ¹ ) _n , R ³ , R ⁸ , (R ⁶ ) _m , X, A and Y (ie, A, Y and AY) are the above general, preferred, more preferred and most preferred definitions. Represents.

  Likewise, preferred compounds of the invention are compounds of the general formulas (Ia), (Ib), (Ic), (Id), (Ie), (If) and (Ig) shown in Tables 1 to 7, in particular Are the specific compounds listed in Tables 1-7.

  The compounds of the invention of general formula (I) may have a chiral carbon atom.

  According to the ranking rule (CIP rule) by Khan Ingold Prelog, these substituents can have (R) or (S) configuration.

The present invention includes compounds of general formula (I) having both (S) and (R) configurations at a particular chiral carbon atom, wherein each carbon atom to which the present invention is directed is independently
(1) It is meant to cover compounds having (R) configuration; or (2) (S) configuration.

Where there are multiple chiral centers in a compound of general formula (I) or formula (IA) to (ID), any desired combination of the configurations of these chiral centers is possible, which is (1) one The chiral center can have an (R) configuration and other chiral centers can have an (S) configuration;
(2) one chiral center can have an (R) configuration and another chiral center can have an (R) configuration; and (3) one chiral center has an (S) configuration; It means that other chiral centers can have the (S) configuration.

  The compounds of the formula (I) are likewise any diastereomers or enantiomers present, as well as the E / Z isomers and salts and N-oxides of the compounds of the formula (I) and their use in the control of animal pests Is included.

  The invention further relates to the use of the compounds of the invention of general formula (I) in the production of agricultural chemicals.

  The invention further relates to compounds of the invention of the general formula (I) and / or salts thereof with a bioactive content of> 0.00000001% by weight, preferably> 0.001% to 95% by weight, based on the weight of the pesticide It relates to pesticides.

  The present invention also relates to a method for controlling animal pests by allowing the compound of the general formula (I) to act on the animal pests and / or the habitats of the animal pests.

  The active ingredients of the present invention with good plant tolerance, favorable isothermal animal toxicity and good environmental compatibility are useful for protecting plants and plant organs, for increasing yields, for improving crop quality, and for animal pests. Especially suitable for agriculture, horticulture, livestock, forest, garden and leisure facilities, protection of stored products and materials, and control of insects, arachnids, worms, nematodes and mollusks encountered in the sanitation sector. They can preferably be used as crop protection agents. They are usually active against sensitive and resistant species, and active against all or some stages of development. The above pests include the following.

  From the order of the Phthiraptera, for example, Damalinia spp., Haematopinus spp., Linognathus spp., Pediculus sp. spp.).

  From the Arachnida net, for example, Acarus spp., Aceria sheldoni, Acrops spp., Aculus spp., Amblus sp. .), Amphitetranichus vienensis, Argas spp., Boophilus spp., Brevipalpus spp., Briobia praeosa Species (Chorioptes spp.), Delmanissas Galinae (Dermanyss) us gallinae), Eutetranychus spp., Epitrimerus spiri, Eutetranychus spp., Eriophys spp. ), Hemitarsonemus spp., Hyalomma spp., Ixodes spp., Latrodectus mactans, et. Species (Nuphersa spp.), Ori Oligonychus spp., Ornithodoros spp., Panonychus spp., Phyllocoptruta olivos, Polyphagotus t. Psoroptes spp.), Rhipicephalus spp., Rhizoglyphus spp., Sarcoptus spp. ), Tarsonemus spp., Tetranychus spp., Vasates lycopersici.

  From the class of Bivalva, for example, Dreissena spp.

  From the order of the Chilopoda, for example, Geophilus spp., Scutigera spp.

  From the order of the Coleoptera, for example, Acalymma vitatum, Acanthoselides obectus, Adoretus spp., Aglastica alpite, Agelastic spp. .), Amphimalon solstitialis, Anobium punctatum, Anoplophorus sp., Anthomonas sp., Anthonomus sp. Species (Apion spp.), Apogonia spp., Atomaria spp., Atagenus spp., Bruchidius obectus, Brucus sp. Species (Cassida spp.), Cerotoma trifurcata (Cetorrhynchus spp.), Chaetocnema spp., Clenus genus C Cosmopolites spp., Costerito・ Cystelandra zelandica, Ctenicera spp., Curculio spp., Cryptrinhyus lapathi, Cindrocopter der. spp.), Diabrotica spp., Dichocrosis spp., Dilobodarus spp., Epilacna spp., Epitrics x ), Faustinus spp., Gibbium psylloides, Herula undalis, Heteronychus heter, Heteronyx ph. elegans, Hylotrupes bajulus, Hypera postica, Hypothenemus spp., Lacnosterna sp. Neata (Leptinotarsa decmlineata), Lucoptera spp., Lissohoptrus oryzophylus, Lixus spp., L. ps. Megascelis spp., Melanotus spp., Meligethes aeneus, Melolonatha spp., Migdolus spp., Migdolus spp. ), Naupactus xanthographs (Naup) ctus xanthographus), Niputsusu-Hororeukusu (Niptus hololeucus), Orikutesu-Rinoserosu (Oryctes rhinoceros), Oryza Efiru vinegar Surinamenshisu (Oryzaephilus surinamensis), Orizafagasu oryzae (Oryzaphagus oryzae), Ochiorinkusu species (Otiorrhynchus spp.), Okishisetonia-Jukunda (Oxycetonia jucunda), Phedon cochleariae, Phyllophaga spp., Phyllotreta spp. ), Popilia japonica, Premnotripes spp., Psyliodes spp., Ptinus spp., Rizobis ventoli R. Rhizopertha dominica), Cytophylus spp., Sphenophorus spp., Sternechus spp., Symphyletes spp. Tenebrio molitor , Tribolium spp. (Tribolium spp.), Torogoderuma species (Trogoderma spp.), Chikiasu species (Tychius spp.), Kishirotorekasu species (Xylotrechus spp.), Zaburasu species (Zabrus spp).

  From the order of the Collembola, for example, Onychiurus armatus.

  From the order of the Diplopoda, for example, Blaniulus guttulatus.

  From the order of the Diptera, for example, Aedes spp., Agromyza spp., Anastrepha spp., Anopheles spp., Asphonderia sp. (Asphondylia spp.), Bacterocera spp., Bbio horturanus, Califora erythrocephala (C.), Ceratitis capitata (C. , Chrysomya spp., Coclyomia sp. (Coc holliomia spp.), Contarinia spp., Cordylobia anthropofaga, Clex spp., D. custerae sp. Species (Dasyneura spp.), Delia spp., Dermatobia hominis, Drosophila spp., Echinocnemus spi. , Gastrophilus spp., Hydurelia spp. Hydreria spp.), Hylemyia spp., Hypobosca spp., Hypoderma spp., Liriomyza spil. Musca spp., Nezara spp., Oestrus spp., Oscinella frit, Pegomia spp., Phorbia spp. .), Prodiplosis spp. ), Psila rosae, Ragoretis spp., Stomoxys spp., Tabanus spp., Tannia spp., Tenia spp. Tetanops spp.), Tipula spp.

  From the order of the gastropoda, for example, Arion spp., Biomphalaria spp., Bulinus spp., Deroceras spp., Garba Species (Galba spp.), Limnaea spp., Oncomellania spp., Pomacea spp., Succinea spp.

  From the order of the Helminth, for example, Ancylostoma duodenale, Ancylostoma ceylicum, Ansilostoma brasiliensis (Acylostoma sapiens) ), Ascaris rubricoides, Ascaris spp., Brugia malayi, Brugia timori, Spost. C. sp. .), Chronorkis Species (Clonorchis spp.), Cooperia spp., Dicrocoelium spp., Dictyocaurus filaria, Diphylobium lathum (Diphyllumbula throbulus) Meduncenus (Dracunculus medinensis), Echinococcus granulosus (Echinococcus granulosus), Echinococcus multilocaris (Enterobolicus sp.) ), Hemonchus spp., Heterakis spp., Hymenolepis nana, Hyostrongulus spp., Loa Loa di, Loa Lo (Nematodirus spp.), Esophagogostom spp., Opisthorchis spp., Onchocerca volvulus, Ostergo sp. G. . ), Schithosomogen spp., Strongyloides fueleborni, Strongyroides stercoralis, Stronoides s. Thorium, Trichinella spiralis, Trichinella nativa, Trichinella britovi, Trichinella nersoni (Trichinella nersoni) Kinera pseudotuberculosis Pushi Laris (Trichinella pseudopsiralis), Trico Strong Angeles species (Trichostrongulus spp.), Torikyurisu-Torikyuria (Trichuris trichuria), Bancroft yarn worms (Wuchereria bancrofti).

  Furthermore, it is possible to control protozoa such as Eimeria.

  From the order of the Heteroptera, for example, Anasa tristis, Antestiopsis spp., Blissus spp., Calocoris spp., Campylon marri Campylomma libida), Caverelius spp., Simex spp., Collaria spp., Creontiades dilutus, Dacinus p.・ Full cuts (Dichelops furcatus), Diconokoris Hewe Ditticoris hetetti, Dysdercus spp., Euschistus spp., Eurygaster spp. I, Heliopeltis sph. ), Leptocorisa spp., Leptogross phyllopus, Lygus spp., Macropes excavatus, Miridae (Miritae) Nezara species (Nezara spp.), Oebalus spp., Pentomidae, Piesma quadrata, Piezodorus spp., Salus sp. S. (Pseudacysta persea), Rhodnius spp., Sahlbergella singularis, Scaptocoris castanea, Scotinophorus sp. Seed (Tibrac a spp. ), Triatoma spp.

  From the order of the Homooptera, for example, Akythosipon spp., Acrogonia spp., Aeneolamia spp., Agonoscena spp., Agonoscena spp. Aureurodes spp.), Aureurobus barodensis, Aureurothrixus spp., Amuraspai sp. Nostigma piri (Aphanostigma piri), Aphis spp., Arboridia apicalis, Aspidiella spp., Aspidiotus spp., Atanus spp. (Aulacorthum solani), Bemisia spp., Brachycaudus helichrysi, Brachycorus spr., Brevicorus sp. ( Carneocephala fulgida), Keratobakuna-Ranigera (Ceratovacuna lanigera), Kerukopidae (Cercopidae), Keropurasutesu species (Ceroplastes spp.), Kaetoshifon-Furagaefori (Chaetosiphon fragaefolii), Kionasupishisu-Tegarenshisu (Chionaspis tegalensis), Kurorita-Onuki (Chlorita onukii), Chromaphis jugrandicola, Chrysomphalus fixus, Cicadulina mbila, Cocomitr Hari (Coccommy) ilus halli), Cocks species (Coccus spp. ), Cryptomyzus ribis, Dalbulus spp., Dialeurodes spp., Diaphorina spp., Diaspis sp. Drosica spp., Dysapis spp., Dysmicoccus spp., Empoaska spp., Eriosoma sprop., Eriosoma sprop. Species (Erythroneura spp.), Eucelis bilobatus, Ferriscia species (Ferrisi) spp.), Geococcus coffeae, Hieroglyphus spp., Homaloidisca coagulata, Hyalopters arunderia sp. (Idiocerus spp.), Idioscopus spp., Laodelfax striatellus, Lecanium spp., Lepidosaphis sapius spp. mi), Macrosiphum spp., Mahanarva spp., Melanaphis sacchari, Metcalfiella spum. Monellia costalis, Monelliopsis pecanis, Myzus spp., Nasonovia ribisnigri, Nepotetics. ), Nilaparvata lugens, Oncometopia spp., Orthezia praelonga, Parabemisiapiria spr. .), Pemphigus spp., Peregrinus maidis, Phenacoccus spp., Phleomyzus patellilop Phylloxera spp., Pinnaspis aspidistrae, Planococcus spp., Protopulvinaria pyriforma sp. , Pseudococcus spp., Psylla spp., Pteromalus spp., Pyrilla spp., Quadra spidiotus sp.・ Giesa (Quesada gigas), last Rastrococcus spp., Rhopalosifum spp., Saissetia spp., Scaphoides titanus, Schiafis minum s. artigalatus, Sogata spp., Sogataella furcifera, Sugatodes spp., Stoctocephala festinaen, Tetrafina. malayensis), Chinokarisu-Kalia et Folia d (Tinocallis caryaefoliae), Tomasupisu species (Tomaspis spp. ), Toxoptera spp., Trialeurodes spp., Triosa spp., Typhlosyba spp., Unaspis sp. (Viteus vitifolii), Zygina spp.

  From the order of the Hymenoptera, for example, Atalia spp., Diprion spp., Hoplocampa spp., Lasius spp., Monomorium pharaonis (Monomomori phalaonis), Vespa spp.

  From the order of the Isopoda, for example, Armadillidium vulgare, Oniscus asellus, Porcellio scaber.

  From the order of the Isoptera, for example, Achromylmex spp., Atta spp., Cornitermes cumulans, Microtermes ovetices, Species (Odontotermes spp.), Reticulitermes spp.

  From the order of the Lepidoptera, for example, Acronica major, Adoxophys spp., Aedia leucomelas, Agrotis spp. Agrotis spp. Alabama spp.), Amyelois transitella, Anarsia spp., Anticarsia spp., Argyroprose spr. Volbo cinnara, Bucuratrix sul Veriella (Bucculatrix turberiella), Bupulseus pianarius, Busseola spp., Cacoecia spp., Calopitial sapora Pomonella (Carpocapsa pomonella), Carposina nipponensis (Ceposina nipponensis), Keimatobia burumata (Chimatobia brayata), Chiro spp. Sia ambiguella), Cnaphalocerus spp., Cnephasia spp., Conoporphasia spp., Conopratia sp., Conopratia sp. Genus species (Cydia spp.), Dalaka noctuides, Diaphania spp., Diatraea saccharalis, Earias sptoE d. aurantium), Euraumopa Path Rigunoserasu (Elasmopalpus lignosellus), Erudana-Sakkarina (Eldana saccharina), Ephestia-Kuefuniera (Ephestia kuehniella), Epinochia species (Epinotia spp. ), Epiphyas postvittana, Etiella spp., Eulia spp., Eupoisia abiguella, Euprotis sp. (Euxoa spp.), Feltia spp., Galleria Melonella, Gracilaria spp., Grafolitha spp., Heedlep sp. , Helicoverpa spp., Heliosth (Helioth) s spp.), Hofmannophila pseudospretella, Homoeosoma spp., Homona spp. ), Raphygma spp., Laspeyresia molesta, Leucinodes orbonalis, Leucoptera spp. Ol, Lisocoptera spp. (Lithophane antennata), Lobesia spp., Loxagrotis albicosta, Lymantria spp., Lyonetia marp. , Maruka testulalis, Mamestra brassicae, Mocis spp, Mythymna seprata, Nymphala spp. ), Oiketicus spp., Oria spp., Ortaga spp., Ostrinia spp., Ourema oryzae, Pula flamena), Parnara spp., Pectinophora spp., Perileucoptera spp., Phlorimaea spp. Genus species (Phyllonocyte spp.), Pieris sp. .), Platynota stultana, Plusia spp., Plutella xylostella, Prices spp., Prodenia spp., Prodenia spp. Protopacese spp.), Pseudoaltia spp., Pseudoplusia includens, Pyrusuta nubilalis, Rachiprusu s. , Schirpofaga sp (Sirpophaga sp p.), Scotia segetum, Sesamia spp., Sparganotis spp., Spodoptera spp., St. pods sp. Subsecivera (Stomopterix subsecivella), Synanthedon spp., Tessia solanivora, Temesia genitali (Termesia gemmatalis) Species (Tortrix spp. ), Trichoplusia spp., Tuta absoluta, Virachola spp.

  From the order of the Grasshopper, for example, Acheta domesticis, Blatta orientalis, Bratella germanica, Dictroplus sp. , Leucophaea madeerae, Locusta spp., Melanoplus spp., Periplaneta americana, Re.

  From the order of the Siphonaptera, for example, Ceratophyllus spp., Xenopsila cheopes.

  From the order of the Symphyla, for example, Scutigella spp.

  From the order of the Thysanoptera, for example, Anapholipus obscurus, Variotropen sra sr. spp.), Heliotrips spp., Hercinostrips femorialis, Ripiforotrips cruentats, Skilled slips (Scirtotrips spp.), Taeniotrips cardamoni, Srips spp.

  From the order of the Thysanura, for example, Lepisma saccharina.

  Examples of plant parasitic nematodes include, for example, Anguina species (Aphelenchoides spp.), Bursaferenchus spp., Ditylenchus spp., Globodera spp., Heterodella spp. Species (Heterodera spp.), Longidorus spp., Meloidogyne spp., Pratylenchus spp., Radforus simporis (Radophorus simporis) .), Tylenchulus semipenetr ans), and Xifinema spp.

  Where appropriate, the compounds of the formula (I) can be used as herbicides, safeners, growth regulators or agents that improve the properties of plants, or as microbicides, eg fungicides, at certain concentrations or application rates. It can also be used as an antifungal, bactericidal, virucidal (including drugs against viroids) or as drugs against MLO (mycoplasma-like microorganisms) and RLO (rickettsia-like microorganisms). If appropriate, they can also be used as intermediates and precursors in the synthesis of other active ingredients.

  The invention further relates to crop protection compositions such as irrigation, instillation and spray solutions and / or formulations such as pesticides and application forms prepared therefrom comprising at least one active ingredient of the invention. These application forms include crop protection agents and / or pesticides, and / or activity enhancing aids such as penetrants (examples include vegetable oils such as rapeseed oil, sunflower oil, mineral oil such as liquid paraffin, rapeseed oil or large Alkyl esters or alkanol alkoxylates of vegetable fatty acids such as methyl esters of soybean oil, and / or spreading agents such as alkyl siloxanes, and / or salts (examples include organic or inorganic ammonium or phosphonium salts, Examples include ammonium sulfate or diammonium hydrogen phosphate), and / or retention promoters such as dioctyl sulfosuccinate or hydroxypropyl guar polymers and / or humectants such as glycerin and / or eg ammonium, potassium It may further include a fertilizer, such as arm or phosphorus-based fertilizers.

  Examples of typical formulations include liquid (SL), emulsion (EC), emulsion formulation (EW), suspension concentrate (SC, SE, FS, OD), granule wettable powder (WG), granule (GR) and capsule concentrate (CS). For these and other possible forms of preparation, see, for example, Crop Life International and in Pesticide Specials, Manual on development and use of FAO and WHO specifications for pestications. Meeting on Pesticide Specifications, 2004, ISBN: 9251048576. These formulations can contain active agrochemical compounds in addition to one or more of the active ingredients of the present invention.

  The subject formulations and application forms are preferably bulking agents, solvents, spontaneous promoters, carriers, emulsifiers, dispersants, frost protectants, biocides, thickeners and other adjuvants and / or other such as adjuvants Of supplements. The adjuvant in this connection is a component that enhances the physiological effect of the preparation without itself having physiological activity. Examples of adjuvants include agents that promote retention, spreading, attachment or penetration on the leaf surface.

  Its active ingredients include liquids, emulsions, wettable powders, aqueous and oil suspensions, powders, dusts, pastes, soluble powders, soluble granules, spray granules, suspoemulsion preparations, active ingredients It can be converted into common formulations such as impregnated natural materials, synthetic materials impregnated with active ingredients, fertilizers and microcapsules in polymer substrates.

  These formulations are prepared in a known manner, for example with the aid of surfactants, ie emulsifiers and / or dispersants and / or blowing agents, as appropriate, with active compounds and extenders, ie liquid solvents and / or solid carriers. The formulation, prepared by mixing, is prepared before or at the time of application in a suitable plant or the like.

  Adjuvants used are some technical for active ingredient formulations and / or application forms produced from these formulations (eg pesticides or crop protection compositions such as spray liquor or seed dressings). It can be a material suitable for imparting specific characteristics such as characteristics and / or specific physiological characteristics. Typical useful adjuvants are bulking agents, solvents and carriers.

  Suitable bulking agents are, for example, water, polar and nonpolar liquid organic chemicals such as aromatic and non-aromatic hydrocarbon groups (paraffins, alkylbenzenes, alkylnaphthalenes, chlorobenzenes, etc.), alcohols And polyhydric alcohols (optionally substituted, etherified and / or esterified), ketones (acetone, cyclohexanone, etc.), esters (fats and oils, etc.) and (poly) ethers From the group of unsubstituted and substituted amines, amides, lactams (such as N-alkylpyrrolidones) and lactones, sulfones and sulfoxides (such as dimethyl sulfoxide).

  In principle, all suitable solvents can be used. When the extender used is water, for example, an organic solvent can be used as a co-solvent. Substantially suitable liquid solvents are aromatics such as xylene, toluene or alkylnaphthalenes, chlorinated aromatic and chlorinated aliphatic hydrocarbon groups such as chlorobenzenes, chloroethylenes or methylene chloride, cyclohexane or paraffins. Aliphatic hydrocarbon groups such as petroleum fractions, mineral and vegetable oils, alcohols such as butanol or glycol and their ethers and esters, ketones such as acetone, methyl ethyl ketone, methyl isobutyl ketone or cyclohexanone, dimethyl sulfoxide, etc. Strong solvents and water.

  In principle, all suitable carriers can be used. Suitable solid carriers are in particular pulverized natural materials such as ammonium salts and kaolins, clays, talc, chalk, quartz, attapulgite, montmorillonite or diatomaceous earth and pulverized synthetic minerals such as finely divided silica, alumina and silicates. Suitable solid carriers for granules include, for example, crushed and fractionated natural rocks such as calcite, marble, pumice, gizzard and dolomite and synthetic granules and paper of inorganic and organic meal, sawdust, coconut shell, corn Granules of organic materials such as cobs and tobacco stems.

  It is also possible to use liquefied gas extenders or solvents. Particularly suitable are extenders or carriers that are gases at standard temperatures and pressures, such as aerosol high pressure gases such as halogenated hydrocarbons and butane, propane, nitrogen and carbon dioxide.

  Examples of ionic or nonionic emulsifiers and / or foaming agents, dispersants or wetting agents or mixtures of these surface-active substances include polyacrylic acid salts, lignosulfonic acid salts, phenolsulfonic acid or Naphthalene sulfonic acid salts, polycondensates of ethylene oxide with fatty alcohols, fatty acids or fatty amines with substituted phenols (preferably alkylphenols or arylphenols), salts of sulfosuccinic acid esters, taurine derivatives (Preferably alkyl taurates), phosphates of polyethoxylated alcohols or phenols, fatty acid esters of polyhydric alcohols and sulfates, derivatives of compounds containing sulfonates and phosphates, eg alkylaryl poly Glico Ethers, alkyl sulfonates, alkyl ethers sulfates, aryl sulfonates, proteins hydrolysates, there is lignosulfite waste liquors and methylcellulose. The presence of a surface-active substance is advantageous when one of the active ingredients and / or one of the inert carriers is insoluble in water and the application is carried out in water.

  Useful emulsifiers and / or foam formers are in particular, for example, polyoxyethylene fatty acid esters, polyoxyethylene fatty alcohol ethers such as alkylaryl polyglycol ethers, alkyl sulfonates, alkyl sulfates, aryl sulfonates and proteins. Nonionic and anionic emulsifiers such as hydrolysates. Suitable dispersants are nonionic and / or ionic substances such as alcohol-POE and / or POP-ethers, acids and / or POP-POE esters, alkylaryl and / or POP-POE ethers, fat- And / or POP-POE adducts, POE- and / or POP-polyhydric alcohol derivatives, POE- and / or POP-sorbitan-or-sugar adducts, alkyl or aryl sulfates, alkyl- or aryl sulfonates and phosphorus From the group of acid alkyl or aryl or corresponding PO-ether adducts. In this context, POP means polyoxypropylene oxide, POE polyoxyethylene oxide, PO propylene oxide and EO ethylene oxide. In addition, there are suitable oligomers or polymers, such as those derived from vinylic monomers, from acrylic acid, from EO and / or PO alone or in combination with, for example, (poly) alcohols or (poly) amines. It is also possible to use lignin and its sulfonic acid derivatives, unmodified and modified celluloses, aromatic and / or aliphatic sulfonic acids and their adducts with formaldehyde.

  Formulate natural and synthetic polymers in the form of latex such as carboxymethylcellulose, powder, granules or gum arabic, polyvinyl alcohol and polyvinyl acetate, and natural and synthetic phospholipids such as kephalins and lecithins Can be used.

  Inorganic pigments such as iron oxides, titanium oxides and Prussian blue dyes and organic dyes such as alizarin dyes, azo dyes and metal phthalocyanine dyes and micronutrients such as iron, manganese, boron, copper, cobalt, molybdenum and zinc salts It is possible to use.

  If appropriate, further additives can be present in the formulation and the application forms derived therefrom. Further possible additives are nutrients (including micronutrients) such as fragrances, mineral or vegetable oils, suitably modified oils, waxes and salts of iron, manganese, boron, copper, cobalt, molybdenum and zinc. Further additives are for example fragrances, protective colloids, binders, adhesives, thickeners, thixotropic substances, penetrants, retention promoters, stabilizers, sequestering agents, complexing agents, humectants, spreading agents. It is. In general, the active ingredient can be combined with any solid or liquid additive commonly used for formulation purposes.

  Stabilizers such as low temperature stabilizers, preservatives, antioxidants, light stabilizers or other agents that improve chemical and / or physical stability may also be present.

  Suitable retention promoters include, for example, all materials that reduce dynamic surface tension such as dioctyl sulfosuccinate or increase viscoelasticity such as hydroxypropyl guar polymers.

  Suitable penetrants in the context of the present invention include all substances typically used for the purpose of increasing the penetration of active agrochemical compounds into plants. In this context, penetrants increase the mobility of the active compounds in the stratum corneum by allowing them to penetrate the stratum corneum of plants from (typically aqueous) application liquids and / or from spray coatings. Defined by This characteristic can be confirmed using the method described in the literature (Baur et al., 1997, Pesticide Science 51, 131-152). Examples include alcohol alkoxylates such as coconut aliphatic ethoxylate (10) or isotridecyl ethoxylate (12), fatty acid esters such as rapeseed oil or soybean oil methyl esters, tallow amine ethoxylate (15), etc. Aliphatic amine alkoxylates or ammonium salts such as ammonium sulfate or diammonium hydrogen phosphate and / or phosphonium salts.

  The formulation preferably comprises 0.00000001 to 98% by weight of active ingredient, more preferably 0.01 to 95% by weight of active ingredient, most preferably 0.5 to 90% by weight of active ingredient, based on the weight of the formulation. .

  The active ingredient is in its commercial standard formulation and in the application form prepared from that formulation, pesticides, attractants, sterilants, bactericides, acaricides, nematicides, fungicides, growth It can be present in a mixture with other active agrochemical components such as regulators, herbicides, safeners, fertilizers, informational substances or with agents to improve plant properties.

  When used as an insecticide, the active ingredient of the present invention can also be present in its commercial standard formulation and in an application form prepared from that formulation in a mixture with a synergist. The synergist is a compound that does not require the synergist itself to be active but enhances the action of the active ingredient.

  When used as an insecticide, the active ingredient of the present invention is in its commercial standard formulation and in an application form prepared from that formulation in the plant environment, on the surface of plant parts or after application on plant tissues It can also be present in a mixture with an inhibitor that prevents degradation of the active ingredient.

  The active ingredient content of application forms (pesticides) prepared from commercial standard formulations can vary within wide limits. The active ingredient concentration of the application form can be from 0.00000001 to 95% by weight active ingredient, preferably from 0.00001 to 1% by weight, based on the weight of the application form.

  Application is carried out by a general method suitable for the application form.

  The treatment of plants and plant parts with the active ingredient of the present invention can be carried out by general treatment methods such as immersion, spraying, atomization, irrigation, evaporation, dusting, cloud fogging, spraying, foaming, application, spreading, injection, watering ( Irrigation), by trickle irrigation, and in the case of breeding, especially in the case of seeds, by dry seed dressing, wet seed dressing, slurry seed dressing, by coating, by coding with one or more coating agents, etc. Do it directly or by acting on it's environment, growing place or storage place. It is also possible to disperse the active ingredient by the ultra-trace method, or to inject the active ingredient preparation or the active ingredient itself into the soil.

  A preferred direct treatment of plants is a foliage treatment. That is, the active ingredient of the present invention is applied to leaves, and in that case, it is possible to adjust the number of treatments and the amount applied to the infection pressure of a specific pest.

  In the case of systemically active compounds, the active ingredient of the present invention is taken up by plants through the root structure. In that case, the plant is treated by the action of the active ingredient of the present invention on the place of growth of the plant. This can be done, for example, by irrigating or mixing soil or nutrient solution. That is, the plant location (eg, soil or hydroponic system) is impregnated with the active ingredient of the present invention in liquid form or by soil application. That is, the active ingredient of the present invention is introduced into the plant location in solid form (eg in the form of granules). In the case of paddy rice crops, this can also be done by metering the compound of the invention in solid application form (eg granules) into a paddy field filled with water.

  The active ingredient of the present invention can be used as it is or in a formulation thereof, and further in a mixture with known fungicides, bactericides, acaricides, nematicides or insecticides, for example, to provide a spectrum of action. It can be expanded or the development of resistance can be hindered. In many cases, a synergistic effect is obtained. That is, the potency of the mixture is higher than the sum of the potencies of the individual compounds.

  Useful mixing partners include, for example, the following compounds.

Is the active ingredient identified here by the generic name of insecticide / acaricide / nematicide known, is it described in the Agricultural Handbook ("The Pesticide Manual", 14th Ed., British Crop Protection Council 2006) Or from the Internet (e.g., http://www.alanwood.net/pesticides).

(1) Acetylcholinesterase (AChE) inhibitors, such as
Carbamates such as alaniccarb, aldicarb, bendiocarb, benfuracarb, butocarboxyme, butoxycarboxym, carbaryl, carbofuran, carbosulfan, etiophencarb, fenobucarb, formethanate, furthiocarb, isoprocarb, methiocarb, mesomil, metorcarb, oxamyl, pirimicarb Thiodicarb, thiophanox, triazamate, trimetacarb, XMC and xylylcarb; or organophosphates such as acephate, azamethiphos, azinephos (-methyl, -ethyl), kazusafos, chlorethoxyphos, chlorfenvinphos, chlormefos, Chlorpyrifos (-methyl), coumaphos, cyanophenphos, demeton-S-methyl, Diazinon, dichlorvos / DDVP, dicrotophos, dimethoate, dimethylvinphos, disulfoton, EPN, ethion, etoprophos, famfur, phenamiphos, fenitrothion, fenthion, phostiazete, heptenophos, isofenphos, O- (methoxyaminothiophosphoryl) salicythione thiothiothione , Mecarbam, methamidophos, methidathion, mevinphos, monocrotophos, nared, ometoate, oxydemeton-methyl, parathion (-methyl), phentoate, folate, hosalon, phosmet, phosphamidone, phoxime, pyrimiphos (-methyl), profenophos, propetamphos, prothiophos, Pyraclofos, pyridafenthione, quinalphos, sulfotep Tebupirimfos, temephos, terbufos, tetrachlorvinphos, thiometon, triazophos, trichlorfon and vamidothion.

(2) GABA-dependent chloride channel antagonists such as organochlorines such as chlordane and endosulfan (α-), or fiprols (phenylpyrazoles) such as ethiprole, fipronil, pyrafluprolol and pyriprole.

(3) Sodium channel modulator / voltage-dependent sodium channel blocker, such as
Pyrethroids such as acrinathrin, allethrin (d-cis-trans, d-trans), bifenthrin, bioaresulin, bioareslin-S-cyclopentenyl, violesmethrin, cycloprotorin, cyfluthrin (β-), cyhalothrin (γ-, λ -), Cypermethrin (α-, β-, θ-, ζ-), ciphenothrin [(1R) -trans isomer], deltamethrin, dimefurthrin, empentrin [(EZ)-(1R) isomer], esfenvale Rate, etofenprox, fenpropatoline, fenvalerate, flucitrinate, flumethrinate, fulvalinate (τ-), halfenprox, imiprotolin, metoflutrin, permethrin, phenothrin [(1R) -trans isomer], praretrin, prof Luthrin, pyrethrins (insecticidal chrysanthemum), resmethrin, RU15525, silafluophene, tefluthrin, tetramethrin [(1R) -isomer], tralomethrin, transfluthrin and ZXI8901, or DDT; or methoxychlor.

(4) nicotinic acetylcholine receptor agonists such as neonicotinoids such as acetamiprid, clothianidin, dinotefuran, imidacloprid, nitenpyram, thiacloprid, thiamethoxam; or nicotine.

(5) allosteric acetylcholine receptor modulator (agonist), for example,
Spinosyn systems such as spinetoram and spinosad.

(6) Chloride channel activator, such as
Evermectins / milbemycins such as abamectin, emamectin benzoate, lepimectin and milbemectin.

  (7) Juvenile hormone analogs such as hydroprene, quinoprene, methoprene or phenoxycarb; pyriproxyfen.

(8) Active ingredient whose mechanism of action is unknown or unspecified, for example,
Fumigants such as methyl bromide and other alkyl halides; or chloropicrin; sulfuryl fluoride; borax;

  (9) Selective feeding inhibitors such as pymetrozine or flonicamid.

  (10) Tick growth inhibitors such as clofentezin, difluvidazine, hexythiazox, etoxazole.

  (11) Microbial disruptors of insect intestinal membranes, such as Bacillus thuringiensis subsp. Isla Elensis, Bacillus sphaericus, Bacillus thuringiensis subsp. Thuringiensis subsp. Tenebrionis and BT plant proteins such as Cry1Ab, Cry1Ac, Cry1Fa, Cry2Ab, mCry3A, Cry3Ab, Cry3Bb, Cry34 / 35Ab1.

(12) ATP disruptors that are oxidative phosphorylation inhibitors, such as
Diafenthiuron; or organotin compounds such as azocyclotin, cihexatin, phenbutatin oxide; or propargite, tetradiphone.

  (13) Oxidative phosphorylation uncouplers that act by blocking the H proton gradient, such as chlorfenapyr and DNOC.

  (14) Nicotinic acetylcholine receptor antagonists such as bensultap, cartap (hydrochloride), thiocylam and thiosultap (sodium).

  (15) Chitin biosynthesis inhibitor, type 0, for example, benzoylurea series, such as bistrifluron, chlorfluazuron, diflubenzuron, fluazuron, fullcycloxuron, flufenoxuron, hexaflumuron, lufenuron, novallon, Nobiflumuron, Teflubenzuron and Triflumuron.

  (16) Chitin biosynthesis inhibitor, type 1, for example, buprofezin.

  (17) Molting disruptors, such as cyromazine.

(18) ecdysone agonist / disturbant, eg
Diacylhydrazine systems such as chromafenozide, halofenozide, methoxyphenozide and tebufenozide.

  (19) Octopamine agonist, such as amitraz.

  (20) Complex III electron transfer inhibitors such as hydramethylnon, acequinosyl, fluacrylpyrim.

(21) Complex I electron transfer inhibitors, such as those from the group of METI acaricides, such as phenazaquin, fenpyroximate, pyrimidifen, pyridaben, tebufenpyrad, tolfenpyrad; or rotenone (Delice).

  (22) Voltage-gated sodium channel blockers such as indoxacarb; metaflumizone.

  (23) Inhibitors of acetyl-CoA carboxylase, such as tetronic acid derivatives, such as spirodiclofen and spiromesifen; or tetramic acid derivatives, such as spirotetramat.

  (24) Complex IV electron transport inhibitors, such as phosphines, such as aluminum phosphide, calcium phosphide, phosphine, zinc phosphide; or cyanide.

  (25) Complex II electron transport inhibitors, such as cienopyrafen.

  (28) Ryanodine receptor effectors such as diamides such as fulvendiamide, chlorantraniliprole (linaxpyr), cyantraniliprole (siadipyr), and 3-bromo-N- {2-bromo-4- Chloro-6-[(1-cyclopropylethyl) carbamoyl] phenyl} -1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamide (known from WO 2005/077934) or methyl 2- [3 , 5-Dibromo-2-({[3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazol-5-yl] carbonyl} amino) benzoyl] -1,2-dimethylhydrazine-carboxy Rate (known from WO 2007/043677).

  Other active ingredients of unknown mechanism of action, such as azadirachtin, amidoflumet, benzoximate, biphenazate, quinomethionate, cryolite, cyflumethofene, dicohol, fluenesulfone (5-chloro-2-[(3,4,4- Trifluorobut-3-en-1-yl) sulfonyl] -1,3-thiazole), flufenerim, pyridalyl and pyrifluquinazone, as well as products based on Bacillus Farmas (I-1582, BioNeem, Votivo), Known active ingredients.

4-{[(6-Bromopyrid-3-yl) methyl] (2-fluoroethyl) amino} furan-2 (5H) -one (known from WO 2007/115644), 4-{[(6-fluoropyrido-3- Yl) methyl] (2,2-difluoroethyl) amino} furan-2 (5H) -one (known from WO 2007/115644), 4-{[(2-chloro-1,3-thiazol-5-yl) methyl ] (2-fluoroethyl) amino} furan-2 (5H) -one (known from WO 2007/115644), 4-{[(6-chloropyrid-3-yl) methyl] (2-fluoroethyl) amino} furan- 2 (5H) -one (known from WO 2007/115644), 4-{[(6-chloropyrid-3-yl) methyl] (2,2-difluoroethyl) amino} f -2 (5H) -one (known from WO 2007/115644), 4-{[(6-chloro-5-fluoropyrid-3-yl) methyl] (methyl) amino} furan-2 (5H) -one (WO 2007 / 156443), 4-{[(5,6-dichloropyrid-3-yl) methyl] (2-fluoroethyl) amino} furan-2 (5H) -one (known from WO2007 / 115646), 4- { [(6-Chloro-5-fluoropyrid-3-yl) methyl] (cyclopropyl) amino} furan-2 (5H) -one (known from WO 2007/115643), 4-{[(6-chloropyrid-3-yl ) Methyl] (cyclopropyl) amino} furan-2 (5H) -one (known from EP-A-0539588), 4-{[(6-chloropyrido-3- ) Methyl] (methyl) amino} furan -2 (5H) - known from ON (EP-A-0539588), [(6- chloropyridin-3-yl) methyl] (methyl) oxide 1-? ⁴ - Surufani Lidencyanamide (known from WO 2007/149134), [1- (6-chloropyridin-3-yl) ethyl] (methyl) oxide-λ ⁴ -sulfanilidenecyanamide (known from WO 2007/149134) and diastereomers thereof (A) and (B):

（ＷＯ２００７／１４９１３４からも公知）、［（６−トリフルオロメチルピリジン−３−イル）メチル］（メチル）オキシド−λ^４−スルファニリデンシアナミド（ＷＯ２００７／０９５２２９から公知）、スルホクサフロール（やはりＷＯ２００７／１４９１３４から公知）、１１−（４−クロロ−２，６−ジメチルフェニル）−１２−ヒドロキシ−１，４−ジオキサ−９−アザジスピロ［４．２．４．２］テトラデク−１１−エン−１０−オン（ＷＯ２００６／０８９６３３から公知）、３−（４′−フルオロ−２，４−ジメチルビフェニル−３−イル）−４−ヒドロキシ−８−オキサ−１−アザスピロ［４．５］デク−３−エン−２−オン（ＷＯ２００８／０６７９１１から公知）、
１−［２−フルオロ−４−メチル−５−［（２，２，２−トリフルオロエチル）スルフィニル］フェニル］−３−（トリフルオロメチル）−１Ｈ−１，２，４−トリアゾール−５−アミン（ＷＯ２００６／０４３６３５から公知）、
［（３Ｓ，４ａＲ，１２Ｒ，１２ａＳ，１２ｂＳ）−３−［（シクロプロピルカルボニル）オキシ］−６，１２−ジヒドロキシ−４，１２ｂ−ジメチル−１１−オキソ−９−（ピリジン−３−イル）−１，３，４，４ａ，５，６，６ａ，１２，１２ａ，１２ｂ−デカヒドロ−２Ｈ，１１Ｈ−ベンゾ［ｆ］ピラノ［４，３−ｂ］クロメン−４−イル］メチルシクロプロパンカルボキシレート（ＷＯ２００６／１２９７１４から公知）、
２−シアノ−３−（ジフルオロメトキシ）−Ｎ，Ｎ−ジメチルベンゼンスルホンアミド（ＷＯ２００６／０５６４３３から公知）、
２−シアノ−３−（ジフルオロメトキシ）−Ｎ−メチルベンゼンスルホンアミド（ＷＯ２００６／１００２８８から公知）、２−シアノ−３−（ジフルオロメトキシ）−Ｎ−エチルベンゼンスルホンアミド（ＷＯ２００５／０３５４８６から公知）、４−（ジフルオロメトキシ）−Ｎ−エチル−Ｎ−メチル−１，２−ベンゾチアゾール−３−アミン１，１−ジオキサイド（ＷＯ２００７／０５７４０７から公知）および
Ｎ−［１−（２，３−ジメチルフェニル）−２−（３，５−ジメチルフェニル）エチル］−４，５−ジヒドロ−１，３−チアゾール−２−アミン（ＷＯ２００８／１０４５０３から公知）。

(Also known from WO 2007/149134), [(6-trifluoromethylpyridin-3-yl) methyl] (methyl) oxide-λ ⁴ -sulfanilidenecyanamide (known from WO 2007/095229), sulfoxafurol (also WO 2007 No. 149134), 11- (4-chloro-2,6-dimethylphenyl) -12-hydroxy-1,4-dioxa-9-azadispiro [4.2.4.2] tetradec-11-ene-10 -One (known from WO 2006/089633), 3- (4'-fluoro-2,4-dimethylbiphenyl-3-yl) -4-hydroxy-8-oxa-1-azaspiro [4.5] dec-3- En-2-one (known from WO 2008/067911),
1- [2-Fluoro-4-methyl-5-[(2,2,2-trifluoroethyl) sulfinyl] phenyl] -3- (trifluoromethyl) -1H-1,2,4-triazole-5 Amines (known from WO 2006/043635),
[(3S, 4aR, 12R, 12aS, 12bS) -3-[(cyclopropylcarbonyl) oxy] -6,12-dihydroxy-4,12b-dimethyl-11-oxo-9- (pyridin-3-yl)- 1,3,4,4a, 5,6,6a, 12,12a, 12b-decahydro-2H, 11H-benzo [f] pyrano [4,3-b] chromen-4-yl] methylcyclopropanecarboxylate ( Known from WO 2006/129714),
2-cyano-3- (difluoromethoxy) -N, N-dimethylbenzenesulfonamide (known from WO 2006/056433),
2-cyano-3- (difluoromethoxy) -N-methylbenzenesulfonamide (known from WO2006 / 100288), 2-cyano-3- (difluoromethoxy) -N-ethylbenzenesulfonamide (known from WO2005 / 035486), 4 -(Difluoromethoxy) -N-ethyl-N-methyl-1,2-benzothiazol-3-amine 1,1-dioxide (known from WO 2007/057407) and N- [1- (2,3-dimethylphenyl) ) -2- (3,5-Dimethylphenyl) ethyl] -4,5-dihydro-1,3-thiazol-2-amine (known from WO 2008/104503).

Bactericides (1) Ergosterol biosynthesis inhibitors, such as aldimorph, azaconazole, viteltanol, bromconazole, cyproconazole, diclobutrazole, difenoconazole, diniconazole, diniconazole-M, dodemorph, dodemorph acetate, epoxiconazole, Etaconazole, phenalimol, fenbuconazole, fenhexamide, fenpropidin, fenpropimorph, fluquinconazole, flurprimidol, flusilazole, flutriazole, fluconazole, fluconazole-cis, hexaconazole, imazalyl, imazalyl sulfate, imi Benconazole, ipconazole, metconazole, microbutanyl, naphthifine, nuarimol, oxypoconazole, paclobutrazol, pefrazo , Penconazole, piperalin, prochloraz, propiconazole, prothioconazole, piributicalbu, pyrifenox, quinconazole, cimeconazole, spiroxamine, tebuconazole, terbinafine, tetraconazole, triadimephone, triadimenol, tridemorph, triflumizole, Trifolin, triticonazole, uniconazole, uniconazole-p, biniconazole, voriconazole, 1- (4-chlorophenyl) -2- (1H-1,2,4-triazol-1-yl) cycloheptanol, 1- (2, 2-dimethyl-2,3-dihydro-1H-inden-1-yl) -1H-imidazole-5-carboxylate methyl, N ′-{5- (difluoromethyl) -2-methyl-4- [3- ( Trimethylsilyl Propoxy] phenyl} -N-ethyl-N-methylimidoformamide, N-ethyl-N-methyl-N ′-{2-methyl-5- (trifluoromethyl) -4- [3- (trimethylsilyl) propoxy] phenyl } Imidoformamide and O- [1- (4-methoxyphenoxy) -3,3-dimethylbutan-2-yl] -1H-imidazole-1-carbothioate.

  (2) Respiratory inhibitors (respiratory chain inhibitors) such as bixafen, boscalid, carboxin, diflumetrim, fenfram, fluopyram, flutolanil, fluxapiloxad, flametopir, flumeciclox, syn-epimeric racemate 1RS, 4SR, Isopyrazam mixture of 9RS and anti-epimeric racemate 1RS, 4SR, 9SR, isopyrazam (anti-epimeric racemate), isopyrazam (anti-epimeric enantiomer 1R, 4S, 9S), isopyrazam (anti-epimeric enantiomer 1S, 4R, 9R), isopyrazam (syn-epimeric racemic 1RS, 4SR, 9RS), isopyrazam (syn-epimeric enantiomer 1R, 4S, 9R), isopyrazam (syn-epimeric enantiomer 1S, 4) , 9S), mepronil, oxycarboxyl, penflufen, penthiopyrad, sedaxane, tifluzamide, 1-methyl-N- [2- (1,1,2,2-tetrafluoroethoxy) phenyl] -3- (trifluoromethyl) -1H-pyrazole-4-carboxamide, 3- (difluoromethyl) -1-methyl-N- [2- (1,1,2,2-tetrafluoroethoxy) phenyl] -1H-pyrazole-4-carboxamide, 3 -(Difluoromethyl) -N- [4-fluoro-2- (1,1,2,3,3,3-hexafluoropropoxy) phenyl] -1-methyl-1H-pyrazole-4-carboxamide and N- [ 1- (2,4-Dichlorophenyl) -1-methoxypropan-2-yl] -3- (difluoromethyl) -1-methyl-1 - pyrazole-4-carboxamide.

  (3) Respiratory inhibitors (respiratory chain inhibitors) for complex III of the respiratory chain, such as amethoctrazine, amisulbrom, azoxystrobin, cyazofamide, dimoxystrobin, enestroburin, famoxadone, fenamidone, full Oxastrobin, Cresoxime-Methyl, Metominostrobin, Orisatrobin, Picoxystrobin, Pyraclostrobin, Pyrametostrobin, Pyraoxystrobin, Pyribencarb, Trifloxystrobin, (2E) -2 -(2-{[6- (3-Chloro-2-methylphenoxy) -5-fluoropyrimidin-4-yl] oxy} phenyl) -2- (methoxyimino) -N-methylethane (2E) -2- (methoxyimino) -N-methyl-2- (2-{[({(1E) -1- [3- (trifluoromethyl) phenyl] ethylidene} amino) oxy] methyl} Phenyl) ethaneamide, (2E) -2- (methoxyimino) -N-methyl-2- {2-[(E)-({1- [3- (trifluoromethyl) phenyl] ethoxy} imino) methyl] phenyl } Ethanamide, (2E) -2- {2-[({[(1E) -1- (3-{[(E) -1-fluoro-2-phenylethenyl] oxy} phenyl) ethylidene] amino} oxy ) Methyl] phenyl} -2- (methoxyimino) -N-methylethanamide, (2E) -2- {2-[({[(2E, 3E) -4- (2,6-dichlorophenyl) but-3. -En-2-ylidene] } Oxy) methyl] phenyl} -2- (methoxyimino) -N-methylethanamide, 2-chloro-N- (1,1,3-trimethyl-2,3-dihydro-1H-inden-4-yl) Pyridine-3-carboxamide, 5-methoxy-2-methyl-4- (2-{[({(1E) -1- [3- (trifluoromethyl) phenyl] ethylidene} amino) oxy] methyl} phenyl)- 2,4-dihydro-3H-1,2,4-triazol-3-one, (2E) -2- {2-[({cyclopropyl [(4-methoxyphenyl) imino] methyl} sulfanyl) methyl] phenyl } -Methyl 3-methoxyprop-2-enoate, N- (3-ethyl-3,5,5-trimethylcyclohexyl) -3- (formylamino) -2-hydroxybenzamide, 2- {2-[(2,5-dimethylphenoxy) methyl] phenyl} -2-methoxy-N-methylacetamide and (2R) -2- {2-[(2,5-dimethylphenoxy) methyl] phenyl} -2 -Methoxy-N-methylacetamide.

  (4) Mitotic and cell division inhibitors, such as benomyl, carbendazim, chlorphenazole, dietofencarb, ethaboxam, fluopicolide, fuberidazole, pencyclon, thiabendazole, thiophanate-methyl, thiophanate, zoxamide, 5-chloro-7- (4-Methylpiperidin-1-yl) -6- (2,4,6-trifluorophenyl) [1,2,4] triazolo [1,5-a] pyrimidine and 3-chloro-5- (6- Chloropyridin-3-yl) -6-methyl-4- (2,4,6-trifluorophenyl) pyridazine.

  (5) Compounds having multi-site activity, such as Bordeaux solution, captahol, captan, chlorothalonil, copper hydroxide, copper naphthenate, copper oxide, basic copper chloride, copper sulfate, etc., diclofluanide, dithianon, dodine, Dodine free base, farbum, fluorophorpet, holpet, guazatine, guazatine acetate, iminotadine, iminoctadine albecylate, iminoctadine triacetate, mankappa, mancozeb, manneb, methylam, methylam-zinc, oxine-copper, propamidine ), Propineb, sulfur and sulfur agents such as calcium polysulfide, thiuram, tolylfluanid, dineb and ziram.

  (6) Resistance inducers, such as acibenzoral-S-methyl, isotianil, probenazole and thiazinyl.

  (7) Amino acid and protein biosynthesis inhibitors, such as andoprim, blasticidin-S, cyprodinil, kasugamycin, kasugamycin hydrochloride hydrate, mepanipyrim and pyrimethanil.

  (8) ATP production inhibitors such as fentin acetate, fentin chloride, hydroxylated fentin and silthiophan.

  (9) Cell wall synthesis inhibitors such as Bench Avaricarb, Dimethomorph, Flumorph, Iprovaricarb, Mandipropamide, Polyoxins, Polyoxorim, Validamycin A and Varifenalate.

  (10) Lipid and membrane synthesis inhibitors such as biphenyl, chloronebu, dichlorane, edifenphos, etridiazole, iodocarb, iprobenphos, isoprothiolane, propamocarb, propamocarb hydrochloride, prothiocarb, pyrazophos, quintozen, technazen and tolcrophos-methyl.

  (11) Melanin biosynthesis inhibitors such as carpropamide, diclocimet, phenoxanyl, phthalide, pyroxylone and tricyclazole.

  (12) Nucleic acid synthesis inhibitors such as benalaxyl, benalaxyl M (kiraraxyl), bupirimate, cloziracone, dimethylimole, ethylimol, furalaxyl, himexazole, metalaxyl, metalaxyl-M (mefenoxam), ofrase, oxadixyl and oxophosphate.

  (13) Signaling inhibitors such as clozolinate, fenpicuronyl, fludioxonil, iprodione, procymidone, quinoxyphene and vinclozoline.

  (14) Uncouplers such as binapacryl, dinocup, ferrimzone, fluazinam and meptyldinocup.

  (15) Yet another compound, such as benazole, betoxazine, capsimycin, carvone, quinomethionate, clazaphenone, churafeneb, cyflufenamide, simoxanyl, cyprosulfamide, dazomet, debacarb, dichlorophen, dichromedin, diphenzoquat, Diphenzoquat methylsulfate, diphenylamine, ecomat, fenpyrazamine, flumethoverl, fluoromide, fursulfanamide, fluthianyl, fosetyl-aluminum, fosetyl-calcium, fosetyl-sodium, hexachlorobenzene, ilumamycin, metasulfocarb, methylisothiocyanate, metolaphenone, Mildiomycin, Natamycin, Dimethyldithiocarbamate, Nitro Allyl-isopropyl, octyninone, oxamocarb, oxyfentiin, pentachlorophenol and its salt, phenothrin, phosphoric acid and its salt, propamocarb-focetylate, propanocin-sodium, proquinazide, pyrrolnitrin, tebufloquine, teclophthalam, toluniphanide, triazoxide, Trichlamide, zalylamide, 1- (4- {4-[(5R) -5- (2,6-difluorophenyl) -4,5-dihydro-1,2-oxazol-3-yl] -1,3-thiazole -2-yl} piperidin-1-yl) -2- [5-methyl-3- (trifluoromethyl) -1H-pyrazol-1-yl] ethanone, 1- (4- {4-[(5S)- 5- (2,6-difluorophenyl) -4,5-dihydro-1,2-o Sazol-3-yl] -1,3-thiazol-2-yl} piperidin-1-yl) -2- [5-methyl-3- (trifluoromethyl) -1H-pyrazol-1-yl] ethanone, -(4- {4- [5- (2,6-difluorophenyl) -4,5-dihydro-1,2-oxazol-3-yl] -1,3-thiazol-2-yl} piperidine-1- Yl) -2- [5-methyl-3- (trifluoromethyl) -1H-pyrazol-1-yl] ethanone, 1H-imidazole-1-carboxylic acid 1- (4-methoxyphenoxy) -3,3-dimethyl Butan-2-yl, 2,3,5,6-tetrachloro-4- (methylsulfonyl) pyridine, 2,3-dibutyl-6-chlorothieno [2,3-d] pyrimidin-4 (3H) -one, 2- [5-Methyl-3 -(Trifluoromethyl) -1H-pyrazol-1-yl] -1- (4- {4-[(5R) -5-phenyl-4,5-dihydro-1,2-oxazol-3-yl]- 1,3-thiazol-2-yl} piperidin-1-yl) ethanone, 2- [5-methyl-3- (trifluoromethyl) -1H-pyrazol-1-yl] -1- (4- {4- [(5S) -5-phenyl-4,5-dihydro-1,2-oxazol-3-yl] -1,3-thiazol-2-yl} piperidin-1-yl) ethanone, 2- [5-methyl -3- (trifluoromethyl) -1H-pyrazol-1-yl] -1- {4- [4- (5-phenyl-4,5-dihydro-1,2-oxazol-3-yl) -1, 3-thiazol-2-yl] piperidin-1-yl} ethanone, -Butoxy-6-iodo-3-propyl-4H-chromen-4-one, 2-chloro-5- [2-chloro-1- (2,6-difluoro-4-methoxyphenyl) -4-methyl-1H -Imidazol-5-yl] pyridine, 2-phenylphenol and salts thereof, 3,4,5-trichloropyridine-2,6-dicarbonitrile, 3- [5- (4-chlorophenyl) -2,3- Dimethyl-1,2-oxazolidine-3-yl] pyridine, 3-chloro-5- (4-chlorophenyl) -4- (2,6-difluorophenyl) -6-methylpyridazine, 4- (4-chlorophenyl)- 5- (2,6-difluorophenyl) -3,6-dimethylpyridazine, 5-amino-1,3,4-thiadiazole-2-thiol, 5-chloro-N′-phenyl-N ′ (Prop-2-yn-1-yl) thiophene-2-sulfonohydrazide, 5-methyl-6-octyl [1,2,4] triazolo [1,5-a] pyrimidin-7-amine, (2Z) Ethyl 3-amino-2-cyano-3-phenylprop-2-enoate, N- (4-chlorobenzyl) -3- [3-methoxy-4- (prop-2-yn-1-yloxy) phenyl ] Propanamide, N-[(4-chlorophenyl) (cyano) methyl] -3- [3-methoxy-4- (prop-2-yn-1-yloxy) phenyl] propanamide, N-[(5-bromo -3-chloropyridin-2-yl) methyl] -2,4-dichloropyridine-3-carboxamide, N- [1- (5-bromo-3-chloropyridin-2-yl) ethyl] -2,4- Dichloropyridine -3-carboxamide, N- [1- (5-bromo-3-chloropyridin-2-yl) ethyl] -2-fluoro-4-iodopyridine-3-carboxamide, N-{(E)-[(cyclo Propylmethoxy) imino] [6- (difluoromethoxy) -2,3-difluorophenyl] methyl} -2-phenylacetamide, N-{(Z)-[(cyclopropylmethoxy) imino] [6- (difluoromethoxy) -2,3-difluorophenyl] methyl} -2-phenylacetamide, N-methyl-2- (1-{[5-methyl-3- (trifluoromethyl) -1H-pyrazol-1-yl] acetyl} piperidine -4-yl) -N- (1,2,3,4-tetrahydronaphthalen-1-yl) -1,3-thiazole-4-carboxamide, N-methyl- -(1-{[5-Methyl-3- (trifluoromethyl) -1H-pyrazol-1-yl] acetyl} piperidin-4-yl) -N-[(1R) -1,2,3,4- Tetrahydronaphthalen-1-yl] -1,3-thiazole-4-carboxamide, N-methyl-2- (1-{[5-methyl-3- (trifluoromethyl) -1H-pyrazol-1-yl] acetyl } Piperidin-4-yl) -N-[(1S) -1,2,3,4-tetrahydronaphthalen-1-yl] -1,3-thiazole-4-carboxamide, pentyl {6-[({[( 1-methyl-1H-tetrazol-5-yl) (phenyl) methylidene] amino} oxy) methyl] pyridin-2-yl} carbamate, phenazine-1-carboxylic acid, quinolin-8-ol and quino Down-8-ol sulfate (2: 1).

  (16) Further compounds such as 1-methyl-3- (trifluoromethyl) -N- [2 '-(trifluoromethyl) biphenyl-2-yl] -1H-pyrazole-4-carboxamide, N- ( 4'-chlorobiphenyl-2-yl) -3- (difluoromethyl) -1-methyl-1H-pyrazole-4-carboxamide, N- (2 ', 4'-dichlorobiphenyl-2-yl) -3- ( Difluoromethyl) -1-methyl-1H-pyrazole-4-carboxamide, 3- (difluoromethyl) -1-methyl-N- [4 '-(trifluoromethyl) biphenyl-2-yl] -1H-pyrazole-4 Carboxamide, N- (2 ', 5'-difluorobiphenyl-2-yl) -1-methyl-3- (trifluoromethyl) -1H-pyrazole-4-carbo Samido, 3- (difluoromethyl) -1-methyl-N- [4 '-(prop-1-in-1-yl) biphenyl-2-yl] -1H-pyrazole-4-carboxamide, 5-fluoro-1 , 3-Dimethyl-N- [4 '-(prop-1-in-1-yl) biphenyl-2-yl] -1H-pyrazole-4-carboxamide, 2-chloro-N- [4'-(prop- 1-in-1-yl) biphenyl-2-yl] pyridine-3-carboxamide, 3- (difluoromethyl) -N- [4 ′-(3,3-dimethylbut-1-in-1-yl) biphenyl- 2-yl] -1-methyl-1H-pyrazole-4-carboxamide, N- [4 ′-(3,3-dimethylbut-1-in-1-yl) biphenyl-2-yl] -5-fluoro-1 , 3-Dimethyl-1H Pyrazole-4-carboxamide, 3- (difluoromethyl) -N- (4'-ethynylbiphenyl-2-yl) -1-methyl-1H-pyrazole-4-carboxamide, N- (4'-ethynylbiphenyl-2- Yl) -5-fluoro-1,3-dimethyl-1H-pyrazole-4-carboxamide, 2-chloro-N- (4'-ethynylbiphenyl-2-yl) pyridine-3-carboxamide, 2-chloro-N- [4 '-(3,3-Dimethylbut-1-in-1-yl) biphenyl-2-yl] pyridine-3-carboxamide, 4- (difluoromethyl) -2-methyl-N- [4'-(tri Fluoromethyl) biphenyl-2-yl] -1,3-thiazole-5-carboxamide, 5-fluoro-N- [4 ′-(3-hydroxy-3-methylbut- 1-in-1-yl) biphenyl-2-yl] -1,3-dimethyl-1H-pyrazole-4-carboxamide, 2-chloro-N- [4 ′-(3-hydroxy-3-methylbut-1- In-1-yl) biphenyl-2-yl] pyridine-3-carboxamide, 3- (difluoromethyl) -N- [4 ′-(3-methoxy-3-methylbut-1-in-1-yl) biphenyl- 2-yl] -1-methyl-1H-pyrazole-4-carboxamide, 5-fluoro-N- [4 ′-(3-methoxy-3-methylbut-1-in-1-yl) biphenyl-2-yl] -1,3-dimethyl-1H-pyrazole-4-carboxamide, 2-chloro-N- [4 '-(3-methoxy-3-methylbut-1-in-1-yl) biphenyl-2-yl] pyridine- 3-ka Boxamide, (5-bromo-2-methoxy-4-methylpyridin-3-yl) (2,3,4-trimethoxy-6-methylphenyl) methanone and N- [2- (4-{[3- (4 -Chlorophenyl) prop-2-yn-1-yl] oxy} -3-methoxyphenyl) ethyl] -N2- (methylsulfonyl) valinamide.

  All of the aforementioned mixing partners of classifications (1) to (16) can form salts with suitable bases or acids where appropriate, provided that they are based on their functional groups Salt formation can be performed.

  According to the present invention, all plants and plant parts can be treated. Plants are to be understood in the context of the present invention as meaning all plants and plant populations, such as desirable and undesirable wild plants or crops (including natural crops). A crop can be a plant that can be obtained by conventional plant breeding and optimization methods, or by biotechnology and genetic engineering methods, or by a combination of these methods, including transgenic plants, plant breeding Includes plant varieties that may or may not be protected by home rights. Plant parts are to be understood as meaning all parts and organs of above and below ground plants such as buds, leaves, flowers and roots, for example leaves, conifers, stems, stems, flowers, Mention can be made of fruiting bodies, fruits, seeds, roots, tubers and rhizomes. Plant parts also include harvests and vegetative and reproductive growths such as seedlings, tubers, rhizomes, cuts and seeds.

  The treatment of the invention with the active ingredients of the plants and plant parts can be carried out directly or in the case of growths, especially in the case of growth products, by conventional treatment methods such as immersion, spraying, evaporation, atomization, spraying, application, injection, injection. In the case of seeds, this is done by applying the compound to the environment, habitat or storage location by applying one or more coatings.

  As already mentioned above, it is possible to treat all plants and plant parts according to the invention. In a preferred embodiment, wild plant species and plant cultivars, or those obtained by conventional biological breeding methods such as cross-breeding or protoplast fusion, and portions thereof are treated. In a further preferred embodiment, genetic engineering methods, where appropriate, transgenic plants and plant varieties (genetically modified organisms) obtained in combination with conventional methods, and parts thereof are treated. The terms “parts”, “parts of plants” and “plant parts” have already been explained above.

  More preferably, in each case, plants of plant varieties that are commercially available or used are treated according to the invention. Plant varieties are to be understood as meaning plants with novel characteristics (“traits”) obtained by conventional breeding, mutagenesis or recombinant DNA techniques. These can be cultivars, biotypes or genotypes.

  Preferred plants are from the group of useful plants, ornamental plants, lawns, commonly used trees (the trees are used as ornamental plants in public and private areas) and forest trees. It is a plant. Forest trees include trees for producing products made from wood, pulp, paper and parts of trees.

  The term “useful plant” as used in the context of the present invention refers to a crop used as a plant for obtaining food, feed or fuel or for industrial purposes.

  Examples of useful plants that can be treated with the active ingredient of the present invention include the following types of plants. Lawns, vines, cereals such as wheat, barley, rye, oats, rice, corn and millet / sorghum; beets such as sugar beets and feed beets; fruits such as berries, nuts and small Fruit trees such as apples, pears, plums, peaches, almonds, cherry trees and berries such as strawberries, raspberries, blackberries; legumes such as kidney beans, lentils, peas and soybeans; oil crops, For example, rapeseed, mustard, poppy, olive, sunflower, coconut, castor, cacao bean and peanut; cucurbitaceae plants such as pumpkin / pumpkin, cucumber and melon; And jute; citrus fruits such as Range, lemon, grapefruit and tangerine; vegetables such as spinach, lettuce, asparagus, cabbage, carrots, onions, tomatoes, potatoes and peppers; In addition, tobacco, nuts, coffee, eggplant, sugar cane, tea, pepper, grape vines, hops, bananas, latex plants and ornamental plants such as plants, shrubs, deciduous trees and conifers. What is listed here is not meant to be limiting.

  The following plants are considered to be particularly suitable target crops for treatment with the active ingredients of the present invention. Cotton, eggplant, lawn, pomegranate, nuclear fruit, small fruit tree, corn, wheat, barley, cucumber, tobacco, vine, rice, cereals, pear, kidney bean, soybean, rapeseed, tomato, bell pepper, melon , Cabbage, potatoes and apples.

  Examples of trees that can be improved according to the method of the present invention are: Various species of fir (Abies sp.), Various species of Eucalyptus (Eucalyptus sp.), Various species of spruce (Picea sp.), Various species of Pinus (Pinus sp.), Various species of genus (Aesculus sp.), Various species of genus Platanus (Platanus) sp.), various species of genus genus (Tilia sp.), various species of maple genus (Acer sp.), various species of genus Tsuga (Tsuga sp.), various types of genus genus (Fraxinus sp.), various kinds of genus genus (Sorbus sp.), white birch Various genera (Betula sp.), Various species of hawthorn (Crataegus sp.), Various elm species (Ulmus sp.), Various Quercus species (Quercus sp.), Various beech species (Fagus sp.), Various species of Salix sp (Salix sp.) .), Boxwood willow Various genera (Populus sp.).

  Preferred trees that can be improved according to the method of the present invention are: The following tree species of the genus Aesculus: A. hippocastanum, A. pariflora, A. carnea; the following tree species of the genus Platanus: (P. aceriflora), P. occidentalis, Platanus racemosa; Spruce (Picea) tree species: German spruce (P. abies); Pines (Pinus) Tree species: P. radiate, P. ponderosa, Lodge pine, P. sylvestre (P. sylvestr) ), S. pine, P. montecola, P. albicaulis, P. resinosa, P. palustris, P. taeda. , P. flexilis, P. jeffregi, P. baksiana, P. strobes; Eucalyptus, the following tree species: Eucalyptus grange E. grandis), E. globulus, E. camadetis, E. caladentis (E. glandulus). itens), Eukariputsusu-Oburikua (E.obliqua), Eukariputsusu-Regunansu (E.regnans), Eukariputsusu-Pirurarusu (E.pilularus).

  Particularly preferred trees that can be improved according to the method of the present invention are: The following tree species of the genus Pinus: Pinus radiate, P. ponderasa, Lodge pine, P. sylvestre, P. sylvestre, Pinus. The following tree species of the genus Eucalyptus: E. grandis, E. globulus and E. camadentis.

  Particularly highly preferred trees that can be improved according to the method of the present invention are: Horse chestnut, Platanaceae, linden tree, maple tree.

  The present invention is also applicable to turfgrass such as cold region turfgrass and warmland turfgrass.

  Depending on the plant species or plant varieties, their location and growth conditions (soil, weather, growth period, nutrients), the treatment of the present invention may provide a super additive (“synergistic”) effect. Thus, for example, reducing the application rate and / or expanding the activity spectrum and / or increasing the activity of substances and compositions that can be used according to the invention, improving plant growth, increasing resistance to high or low temperatures, drought Or increased tolerance to salt in water or soil, improved flowering ability, simplified harvesting, accelerated maturation, increased yield, improved crop quality and / or increased nutritional value, storage stability of the crop And / or processability can be improved, which exceeds the effects that would actually be expected.

  Transgenic plants or plant varieties (obtained by genetic engineering) that are preferably treated according to the present invention are all plants that have been genetically modified to provide genetic material that confers particularly advantageous and useful traits to these plants. and so on. Examples of such traits include improved plant growth, increased tolerance to high or low temperatures, increased tolerance to drought or salt in water or soil, improved flowering ability, simplified harvesting, accelerated maturation, There is an increase in yield, an improvement in the quality of the harvest and / or an increase in nutritional value, an improvement in the storage stability and / or processability of the harvest. Further, particularly emphasized examples of such traits are improved plant defense against harmful animals and microorganisms such as insects, mites, phytopathogenic fungi, bacteria and / or viruses, and certain herbicidal activities. This is an improvement in plant tolerance to active ingredients. Examples of transgenic plants that may be mentioned include cereals (wheat, rice), corn, soybeans, potatoes, sugar beets, tomatoes, peas and other plant varieties, important crops such as cotton, tobacco, rapeseed, and Mention may be made of fruit plants (fruits include apples, pears, citrus fruits and grapes), but of particular importance are corn, soybeans, potatoes, cotton, tobacco and rapeseed. Particularly emphasized traits are due to toxins formed in plants, in particular genetic material from Bacillus thuringiensis (eg genes CryIA (a), CryIA (b), CryIA (c), CryIIA). , CryIIIA, CryIIIB2, Cry9c, Cry2Ab, Cry3Bb and CryIF, and combinations thereof) increase plant defenses against insects, spiders, nematodes, slugs and snails (below) , Referred to as “Bt plant”). Also of particular interest are the systemic acquired resistance (SAR), cystemin, phytoalexins, elicitors and resistance genes, and the defense ability of plants against fungi, bacteria and viruses by correspondingly expressed proteins and toxins Is an increase. A trait of particular importance is an increase in plant tolerance to certain active ingredients having herbicidal activity, such as imidazolinones, sulfonylureas, glyphosate or phosphinotricin (eg the “PAT” gene). Genes that impart a desired target trait can also be present in combination with each other in the transgenic plant. Examples of “Bt plants” that may be mentioned include YIELD GARD® (eg corn, cotton, soybean), KnockOut® (eg corn), StarLink® (eg corn), Bollgard There are corn varieties, cotton varieties, soybean varieties, and potato varieties sold under the trade names of (registered trademark) (cotton), Nucotn (registered trademark) (cotton) and NewLeaf (registered trademark) (potato). Examples of herbicide-tolerant plants that may be mentioned include Roundup Ready® (resistance to glyphosate, eg corn, cotton, soybean), Liberty Link® (resistance to phosphinotricin, eg rapeseed), IMI There are corn varieties, cotton varieties and soybean varieties sold under the trade names of (registered trademark) (resistance to imidazolinones) and STS (registered trademark) (resistance to sulfonylureas, eg corn). Herbicide-tolerant plants that can be mentioned (plants that have been bred in a conventional manner to confer herbicide tolerance) include varieties sold under the name Clearfield® (eg, corn). . Of course, these statements also apply to plant varieties having these genetic traits or those still to be developed, and such plant varieties will be developed and / or marketed in the future. .

  The plants listed above can be treated according to the invention in a particularly advantageous manner with the compounds of the general formula I and / or the active ingredient mixtures according to the invention. The above mentioned preferred ranges for active ingredients or mixtures also apply to the treatment of these plants. Of particular emphasis is the treatment of plants with the compounds or mixtures specifically described herein.

  Furthermore, the compounds of the present invention are other hygiene pests such as harmful sucking insects, biting insects and plant parasites, stored pests, pests that destroy industrial materials and parasites in the field of animal health. It can be used to control a number of different pests, such as pests, and can be used to control such organisms, such as their elimination and eradication. Therefore, the present invention also includes a method for controlling pests.

  In the animal health sector, ie in the field of veterinary medicine, the active ingredients according to the invention act against animal parasites, in particular ectoparasites or endoparasites. The term “endoparasite” includes in particular helminths such as tapeworms, nematodes or flukes and protozoa such as coccidials. Ectoparasites are typically and preferably arthropods, in particular insects such as flies (bite and lick), parasitic fly larvae, lice, hair lice, lice, fleas etc. or ticks such as tick or soft tick Acarides or mites such as mites, mites, and mites.

  These parasites include the following:

  From the order of the Anoplida, for example, Haematopinus spp., Linognathus spp., Pediculus spp., Phtyrus spp., Phtyrus spp. (Solenopotes spp.). Examples are Rinogunasasu-Setosasu (Linognathus setosus), Rinogunasasu-Bitsuri (Linognathus vituli), Rinogunasasu-Obirasu (Linognathus ovillus), Rinogunasasu-Obiforumisu (Linognathus oviformis), Rinogunasasu-Pedarisu (Linognathus pedalis), Rinogunasasu-Sutenopushisu (Linognathus stenopsis ), Haematopinus asini macrocephalus, Haematopinus eurosternus, Haematopinus suis, Haematopinus suis, Dikyurasu-Fanusu-Kyapitisu (Pediculus humanus capitis), Pedikyurasu-Fanusu-Koruporisu (Pediculus humanus corporis), Firoera-Busta Tricks (Phylloera vastatrix), Fusuirusu-Pyubisu (Phthirus pubis), Sorenopotesu-Kyapiratasu (Solenopotes capillatus).

  From the order of Mallophagida and Amblycerina and Ischnocerina, for example, Trimenopon spp., Menopon spp., Menopon spt. .), Bobicola spp., Wernekiella spp., Lepikentron spp., Damalina spp., Trichodectes sp. Felicola spp. Specific examples include Bobicola bovis, Bobicola ovis, Bobicola limbata, Lamarina bovis (Damarina bovis), Trichodetic sco subrostratus, Bovicola caprae, Lepikentron ovis, Wernekiella equi.

  From the order of the Diptera, and Nematocerina and Brachycerina, for example, Aedes spp., Anopheles spp., Curex genus ( Culex spp.), Simulium spp., Eusimulium spp., Phlebotomas spp., Lutzomia spp., Curicoid sp. Chrysops spp., Odagmia spp., Wilhelmia spp. Hybomitora spp., Atyrolotus spp., Tabanus spp., Haematopota spp., Phillipopy sp. Braula spp.), Musca spp., Hydrotaea spp., Stomoxys spp., Haematobia spp., Morelia sp. Fania spp., Grossina spp., Caliphora spp., Lucilia spp. (Lucili spp.) a spp.), Chrysomya spp., Wohlfahrtia spp., Sarcophaga sp., Oestrus spp., Hipoderma sp. ), Gastrophilus spp., Hippobosca spp., Lipoptena spp., Melophagas spp., Rinospras sp. Genus species (Tipula spp.). Specific examples are Aedes aegypti, Aedes albopictus, Aedes taeniohynchus, Anopheles gambiae, Anopelis gambiale A Phala (Calliphora erythrocephala), Chrysozona pluvialis, Curex quinquefacciatus, Culex pipiex sulcus, Culex pipiens rsalis), Fannia canicularis, Sarcophaga carnaria, Stomoxys calcitrans, Tipura palicula, Sipla palicula Lucilia sericata), Simulium reptans, Frebotos papatasi, Phlebotus longipalpis, Phdagomus longipalpis Uiina (Wilhelmia equina), Bohusora erythrocephala (bophthora erythrocephala), tabanus bromius (Tabanus bromius), tabanus spodotas (Tabanus spodotas) Hybomitra ciurea, Chrysops caecutiens, Chrysops relictus, Hematotopotapolutopalipo toapitatopaparitop ta italica), Musca Autumn Naris (Musca autumnalis), Musca domestica (Musca domestica), Hematobia-Iritansu-Iritansu (Haematobia irritans irritans), Hematobia-Iritansu exigua (Haematobia irritans exigua), Hematobia-stimulation lance (Haematobia stimulans), Hydrotaea irritans, Hydrotaea albipunta, Chrysomya chloropyga, Chrysomya chloropyga Otruss Ovis, Hypoderma bovis, Hyderma lineaum, Pruzhevalskiana is, Mina, B , Lipoptena capreoli, Lipoptena cervi, Hippobosca variegata, Hippobosca espain Hilus intestinalis, Gasterophilus haemorroidalis, Gasterophilus inermis, Gasterophilus nasily, Gasterophilus nigirolis Gasterophilus pecorum), Braula coeca.

  From the order of Siphonaptida, for example, Purex spp., Ctenocephalides spp., Tunga spp., Xenopsilla spp., Xenopsilla spp. Genus species (Ceraphyllus spp.). Specific examples include Ctenocephalides canis, Ctenocephalides ferris, Plexex irritans, Tunga penetrances, Tunga penetrans ps It is.

  From the order of the Heteropterida, for example, Chimex spp., Triatoma spp., Rhodnius spp., Panstromylus spp.

  From the order of the cockroach (Blatartida), for example, Blata orientalis, Periplaneta americana, Blatella germanica (Speron sp., Supella sp.) )).

  From the order of the Acari (Acarina) and the Metastigmatidae and the Mesostigmatidae, for example, Argas spp., Ornithodras spp. .), Ixodes spp., Amblyomma spp., Rhipicephalus (Bopophilus) (spp.), Dermacentor spp. (Haemophysalis spp.), Hyalomma spp., Delmanissus spp. ( Dermanisssus spp.), Rhipicephalus spp. (Original genus of multi-host mites), Ornithonysus spp., Pneumonysus spp., Rye lietia sp Species (Pneumonysus spp.), Sternostoma spp., Barroa spp., Acarapis spp. Specific examples are Argas persicus, Argas persicus Argas reflexus, Ornithodras moubata Otobius megnini, Lipipesphalus (Buophilus) microplus (Rhipicephalus (Boophilus) microplus), Lipicephalas (Buophilus) de Colorados (Boufilus) Ripicephalus (Boophilus) calcerats, Hyaloma anatolicum, Hyaloma aegypticum, Hyalomma marginatum, Hyalomma transiens, Rhipicephalus exusi, Ixodes ricinus, Ixodes ricinus・ Pyrosus, Ixodes rubicundus, Ixodes scapularis, Ixodes holoculus, Hemaphysacon ph. salis concinna), Hemafisarisu-Pankutata (Haemaphysalis punctata), Hemafisarisu-Shin'abarina (Haemaphysalis cinnabarina), Hemafisarisu-Otofira (Haemaphysalis otophila), Hemafisarisu-Reachi (Haemaphysalis leachi), Hemafisarisu-Rongikoruni (Haemaphysalis longicorni), Delmas Centaur-Maruginatasu (Dermacentor marginatus), Dermacentor reticulatus, Dermacentor pictus, Dermacentor Albi Pikutasu (Dermacentor albipictus), Delmas Centaur-Anderusoni (Dermacentor andersoni), Delmas Centaur variabilis (Dermacentor variabilis), Hiaronma-Mauritanikamu (Hyalomma mauritanicum), Ripisefarasu-sanguineus (Rhipicephalus sanguineus), Ripisefarasu - Bursa (Rhipicephalus bursa), Ripisefarasu・ Rhipicephalus appendiculatus, Ripecephalus capensis, Rhipicephalus cranicas (Rhipicephus) lus turanicus), Ripisefarasu-Zanbejienshisu (Rhipicephalus zambeziensis), Anburioma America Nam (Amblyomma americanum), Anburioma-Bariegatamu (Amblyomma variegatum), Anburioma-Makyuratamu (Amblyomma maculatum), Anburioma-Heburaeumu (Amblyomma hebraeum), Anburioma-Kajenensu ( Amblyomma cajnense, Dermanissus gallinae, Ornithonissus bursa, Ornithonissus sylviaram (Ornithonyssus s) lviarum), Valois-Jakobusoni (Varroa jacobsoni).

  From the order of the Actinedida (Prostigmata) and the Acaridida (Astigmata), for example, Acarapis spp., Cheeletia Genus species (Ornithocheyletia spp.), Myobia species (Myobia spp.), Psorergates spp., Demodex spp., Thrombiculospros sp. spp.), Acarus spp., Tyrophagus spp.), Caloglyphus spp., Hypodectes spp., Pterolichus spp., Psoroptes spp., Coroptes sp. Genus species (Otofectes spp.), Sarcoptes spp., Notoeedres spp., Knemidocoptes spp., Cytodites spp. .). Specific examples are Cheyretiella yasuguri, Cheyretiella blackei, Demodex canis, Demodex bovis, Demodex bovis, Demodex visd Demodex caprae, Demodex equi, Demodex cavalli, Demodex suis, Neotrombicula neumbulumula Desirelli (Neotropicula desale) ri), Neoschongastia xerothermobia, Trombicula akamushi, Istoti s petit, S Sarcoptes bovis, Sarcoptes ovis, Sarcoptes rupicaprae (= S. Caprae), Sarcoptes euco (Sarcoptes equip) Psoroptes ovis, Psoroptes cuniculi, Psoroptes eu sid Pneumonysoides caninum, Acarapis woody.

  The active ingredients of the present invention are also suitable for combating arthropods, helminths and protozoa that attack animals. Such animals include cattle, sheep, goats, horses, pigs, donkeys, camels, buffalo, rabbits, chickens, turkeys, ducks, geese, farmed fish and bees. Further, the animals include, for example, pets such as dogs, cats, pet birds, ornamental fish (also called pet animals), and animals known as laboratory animals such as hamsters, guinea pigs, rats and mice. .

  Exterminating these arthropods, helminths and / or protozoa should reduce deaths, improve productivity (for meat, milk, wool, skin, eggs, honey, etc.) and improve host animal health By doing so, it becomes possible to breed animals more economically and easily by using the active ingredient of the present invention.

  For example, it may be desirable to inhibit or interrupt blood uptake from the host by parasites (when relevant). Parasite control can also contribute to preventing transmission of infectious agents.

  The term “disinfect” as used herein with respect to the veterinary field is that the active ingredient acts by reducing the occurrence of the target parasite in an animal infected with such a parasite to an innocuous level. means. More specifically, “disinfect” as used herein means that the active ingredient kills the subject parasite, inhibits its growth, or inhibits its proliferation.

  In general, when used for the treatment of animals, the active ingredients of the present invention can be used directly. Preferably, the components are used in the form of pharmaceutical compositions that may contain pharmaceutically acceptable excipients and / or adjuvants known in the prior art.

  In the veterinary and animal husbandry sectors, for example, intestinal administration in the form of tablets or capsules, pills, liquid medicine, granules, pastes, boluses, feed or in the form of suppositories, or injection (especially muscle Injection, subcutaneous injection, intravenous injection, intraperitoneal injection), implants, parenteral administration such as nasal administration, for example, immersion or immersion, spraying, pouring on and spotting on, washing and dusting The active ingredients are used in a known manner by dermal administration in the form of, and with the aid of molded articles containing the active ingredients, such as collars, ear tags, tail marks, foot rings, end nets, marking tools, etc. (= Administer. The active ingredients can be formulated as shampoos or as suitable formulations which can be used in aerosols or as pressureless sprays such as pump sprays and nebulizer sprays.

  When used on livestock, poultry, pets, etc., the active ingredient of the present invention comprises a formulation (eg, powder, wettable powder [“WP”]) containing the active ingredient in an amount of 1 to 80% by weight, Can be used directly or after dilution (eg, 100 to 10,000 fold dilution) as an emulsion, emulsion [“EC”], free flowing composition, homogeneous solution and suspension concentrate [“SC”]. Yes, or they can be used as a medicine bath.

  When used in the veterinary field, the active ingredient of the present invention can be used in combination with a suitable synergist such as an acaricide, insecticide, rodenticide, protozoa or other active ingredients.

  It has also been observed that the compounds of the invention have a strong insecticidal activity against insects that destroy industrial materials. The invention therefore further relates to the use of the compounds of the invention in protecting industrial materials against infection or destruction by insects.

  The following insects can be mentioned as examples and preferred ones, but are not limited thereto.

Coleoptera (beetles), for example, Hirotorupesu-Bajurusu (Hylotrupes bajulus), Kurorohorusu-Piroshisu (Chlorophorus pilosis), Anobiumu-Punkutatsumu (Anobium punctatum), Kisesutobiumu-Rufobirosumu (Xestobium rufovillosum), Puchirinusu-Pekuchikorunisu (Ptilinus pecticornis), Dendrobium Pertinekis (Dendrobium pertinex), Ernovius mollis, Priobium carpini, Lyctus brunneus, Lyctus rnicus us), Lykutus pranicollis, Lycusus linearis, Lycustus pescens, Trogoxylon aequare (Trogoxylon aequile) ), Tryptodendron spec., Apate monachus, Bostrychus capuchins, Heterobostrus bruneus spp. . C), Jinoderusu-Minutsusu (Dinoderus minutus);
Hymenopterons, for example, Sirex juvencus, Urocerus gigas, Urocerus gigas taignus, Urocerus urus urous g
Termites, for example, Carotermes flavicollis, Cryptothermes brevis, Heterotermes indicola, Reticulimes flaviters Reticulitermes santonensis, Reticulitermes lucifugus, Mastothermes darwiniensis, Zotermopsis nevadensis ), Koputoterumesu Formosa Taunus (Coptotermes formosanus);
Bristles, for example, Lepisma saccharina.

  In the context of the present invention, industrial materials shall mean non-biological materials such as, preferably, plastics, adhesives, sizes, paper and cardboard, leather, wood and processed wood products, and coating compositions. Should be understood.

  The ready-to-use composition can also include another insecticide, if appropriate, and, if appropriate, one or more fungicides.

  As regards possible additional additives, mention may be made of the insecticides and fungicides mentioned above.

  The compounds of the present invention can also be used to protect against contact with salt water or fresh seawater, in particular hulls, screens, nets, buildings, mooring equipment and signal systems.

  Furthermore, the compound of the present invention can be used as an antifouling agent alone or in combination with other active ingredients.

  The active compound is used in domestic, hygiene and storage product protection, and the active ingredient is an animal pest, particularly insects, arachnids found in enclosed spaces such as houses, factory halls, offices, vehicle cabins, etc. It is also suitable for controlling ticks. They can control these pests either alone or in combination with other active ingredients and adjuvants in household insecticide products. They are effective against sensitive and resistant species and are also effective against all developmental stages. These pests include the following:

  From the order of the Scorpionidea, for example, Butus occitanus.

  From the order of the Acarina, for example, Argas persicus, Argas reflexus, Bryobia ssp., Dermanissus gallinae g Ornithodorus moubat, Ripicephalus sanguinus, Trombicula alfreddussi, Neutrombula maduramu Vinegar Puteronishimusu (Dermatophagoides pteronissimus), Dermatophagoides Death Horinae (Dermatophagoides forinae).

  From the order of the Araneae, for example, Avicularidae, Araneidae.

  From the order of Opiliones, for example, Pseudoscorpiones chelifer, Pseudoscorpiones cheiridium, Opiliones phalangium (Opiliones phalionum).

  From the order of the Isopoda, for example, Oniscus asellus, Porcellio scaber.

From the order of the Diplopoda, for example, Blaniulus gutulatus, Polydesmus spp .;
From the order of the Chilopoda, for example, Geophilus spp.

  From the order of the Zygenoma, for example, Ctenolepisma spp., Lepisma saccharina, Lepismodes inquilinus.

  From the order of the cockroach (Blattaria), for example, Blatta orientalies, Bratella germanica, Bratella asahinai, B. phae a la e. , Parcobratta spp., Periplaneta australasiae, Periplaneta americana, Periplaneta P., Periplaneta p. laneta fuliginosa), Spela-Rongiparupa (Supella longipalpa).

  From the order of the Saltatoria, for example, Acheta domesticus.

  From the order of the Dermaptera, for example, Forficula auricularia.

  From the order of the Isoptera, for example, Carotermes spp., Reticulitermes spp.

From the order of the Psocoptera, for example, Repinatus spp., Liposcelis spp.
From the order of the Coleoptera, for example, Anthronus spp., Atagenus spp., Dermestes spp. ), Ptinus spp., Rhizopertha dominica, Sitophilus umte, Sitofilus zei, Sitofilus zei, ).

  From the order of the Diptera, for example, Aedes aegypti, Aedes albopictus, Aedes taenorynchus, Aph. erythrocephala), Chrysozona pluvialis, Clex quinquefasciatus, Clex pipiens, S. genus sp. N. canicularis, Musca domestica, Phlebotomas spp., Sarcophaga carnaria, Symum s. calcitrans), Tipula pardosa.

  From the order of Lepidoptera, for example, Acroia grisella, Galleria melonella, Plodia interpuntella, Tinea pelena Tineola bisselliella.

  From the order of the Siphonaptera, for example, Ctenocephalides canis, Ctenocephalides felis, Plex irritans, Tunga penetrance, et al. (Xenopsilla cheope).

  From the order of the Hymenoptera, for example, Camponotus herculaneus, Lasius friginosus, Lasius niger (Lasius niger (Lasius niger), Paravespula spp., Tetramorium caespitum.

  From the order of the Anoplura, for example, Pediculus humanus capitis, Pediculus humanus corpolis, Pemphigus spp, Pemphigus spp. Puthyrus pubis.

  From the order of the Heteroptera, for example, Simex hemipterus, Simex lectularius, Rhodinus prolixus, Triatoma infestans a.

  In the field of household insecticides, they are used alone or with other suitable active ingredients such as phosphate esters, carbamates, pyrethroids, neonicotinoids, growth regulators or other known Used in combination with an active ingredient selected from the types of insecticides.

  They are aerosols, non-pressurized spray products such as pump sprays and sprays, automatic atomization systems, nebulizers, foams, gels, evaporator products with evaporator tablets made of cellulose or plastic, liquid evaporators, gels and membranes Evaporators, propeller-driven evaporators, energy-free or passive evaporation systems, insect papers, insect bags, and insects, as gels or powders, for spreading Used in bait or at bait station.

Description of Methods and Intermediates The present invention relates to compounds of general formula (I):

（式中、Ｑ^１からＱ^８、Ｒ^１からＲ^６、Ａ、Ｘ、Ｙ、Ｖ、ｍおよびｎはそれぞれ上記のように定義される。）の製造方法であって、
ａ）下記一般式（ＩＩＩ）のアミン：

(Wherein Q ¹ to Q ⁸ , R ¹ to R ⁶ , A, X, Y, V, m and n are each defined as above),
a) Amines of the following general formula (III):

を下記一般式（ＩＩ）のカルボン酸またはカルボニルハライド：

A carboxylic acid or carbonyl halide of the following general formula (II):

（式中、Ｌはハロゲンまたはヒドロキシルである）と反応させて、ＷがＯ（酸素原子）である一般式（Ｉ）の化合物を得て、そして
ｂ）適宜に、ＷがＯ（酸素原子）である一般式（Ｉ）の化合物を次に、硫化試薬と反応させて、ＷがＳ（硫黄原子）である一般式（Ｉ）の化合物を得る方法に関するものでもある。

(Wherein L is halogen or hydroxyl) to obtain a compound of general formula (I) wherein W is O (oxygen atom), and b) optionally W is O (oxygen atom) The compound of general formula (I) is then reacted with a sulfurizing reagent to obtain a compound of general formula (I) in which W is S (sulfur atom).

The invention also relates to compounds of general formula (I) in which V is R ⁴ , R ⁴ is hydrogen, R ⁵ is hydrogen and W is O. These compounds correspond to the compounds of general formula (I-3) in scheme 3 shown below.

The present invention is also a preferred method for separately producing the compound of the present invention represented by the general formula (I-3) shown in Scheme 3,
a) Amines of the following general formula (III):

を、下記一般式（Ｖ）のアクリル酸誘導体：

An acrylic acid derivative of the following general formula (V):

と反応させて、下記一般式（ＶＩ）のアクリルアミド：

And acrylamide of the following general formula (VI):

を得て、
ｂ）次に、一般式（ＶＩ）のアクリルアミドを、パラジウム触媒の存在下に下記一般式（ＶＩＩ）のハロゲン化合物：

Get
b) Next, an acrylamide of the general formula (VI) is converted into a halogen compound of the following general formula (VII) in the presence of a palladium catalyst:

と反応させて、一般式（Ｉ−３）の化合物（Ｌはハロゲンまたはヒドロキシルであり、Ｌ^１は塩素、臭素、ヨウ素またはトリフレートである）を得る方法に関するものでもある。

It is also related to a method for obtaining a compound of the general formula (I-3) (L is halogen or hydroxyl and L ¹ is chlorine, bromine, iodine or triflate).

  The present invention further relates to a compound of the general formula (VI) obtained as an intermediate in the process for producing the compound of the general formula (I-3). A preferred compound of the general formula (VI) is N- {2,2,2-trifluoro-1- [3- (trifluoromethyl) phenyl] ethyl} -acrylamide, which is prepared in Synthesis Example 2 in Step 1. Are described in the production examples.

  By way of example and further, the preparation of a compound of the invention of formula (I) and a specific compound of the invention of formula (I-3) is illustrated in the following scheme. In this case, reference is also made to production examples.

  Schemes 1 to 6 show, in general form, how the compounds of the invention of formula (I) can be obtained by the process according to the invention when W = O. The compound of general formula (I) in which W = O is referred to as general formula (I-1) below. Compounds of the invention of the formula (I) in which W = S can be obtained therefrom by reaction with sulfurizing reagents such as Lawesson's reagent, ammonium sulfide or diphosphorus pentasulfide.

  Schemes 7 to 10 show how the compounds of formula II can be obtained.

  Schemes 11 to 21 show how to obtain specific compounds of general formula I.

Regarding these diagrams and their description, Q ¹ to Q ⁸ , R ¹ to R ⁶ , A, X, Y, V, m, and n are given different definitions in the description of the individual diagrams in the following description. Unless otherwise defined, each is as defined above.

Scheme 1 (Production of compounds of general formula I)

一般式（Ｉ−１）の本発明の化合物は、図式１に示した方法に従って（Ｌはハロゲンまたはヒドロキシルである）、一般構造（ＩＩＩ）のアミンを一般構造（ＩＩ）の活性化カルボン酸誘導体と反応させることで得ることができる。（ＩＩ）については、第１に、塩基、例えばトリエチルアミンまたは水酸化ナトリウムの存在下に酸ハライド（例：Ｌ＝塩素）を用いることが可能である。第２に、カルボン酸（Ｌ＝ＯＨ）も用いることができるが、ただしカップリング試薬、例えばジシクロヘキシルカルボジイミドおよび１−ヒドロキシベンゾトリアゾールなどの添加剤を用いる［Ｃｈｅｍ． Ｂｅｒ． １９７０， ７８８］。１−エチル−３−（３−ジメチルアミノプロピル）カルボジイミド、１，１′−カルボニル−１Ｈ−イミダゾールおよび類似の化合物などのカップリング試薬を用いることも可能である。その製造方法を実施するのに用いられるカップリング試薬は、エステルまたはアミド結合を作る上で好適なもの全てであることができる（例えば、Ｂｏｄａｎｓｋｙ ｅｔ ａｌ．， Ｐｅｐｔｉｄｅ Ｓｙｎｔｈｅｓｉｓ， ２ｎｄ ｅｄ．， Ｗｉｌｅｙ ＆ Ｓｏｎｓ， Ｎｅｗ Ｙｏｒｋ， １９７６； Ｇｒｏｓｓ， Ｍｅｉｅｎｈｏｆｅｒ， Ｔｈｅ Ｐｅｐｔｉｄｅ： Ａｎａｌｙｓｉｓ， Ｓｙｎｔｈｅｓｉｓ， Ｂｉｏｌｏｇｙ（Ａｃａｄｅｍｉｃ Ｐｒｅｓｓ， Ｎｅｗ Ｙｏｒｋ， １９７９を参照）。さらに、（Ｉ）の製造に混合無水物を用いることも可能である［Ｊ． Ａｍ． Ｃｈｅｍ． Ｓｏｃ．， １９６７， ５０１２］。この方法では、各種のクロルギ酸エステル類、例えばクロルギ酸イソブチル、クロルギ酸イソプロピルを用いることが可能である。同様に、そのためにジエチルアセチルクロライド、トリメチルアセチルクロライドなどを用いることが可能である。

The compound of the present invention of general formula (I-1) is prepared by converting an amine of general structure (III) to an activated carboxylic acid derivative of general structure (II) according to the method shown in Scheme 1 (L is halogen or hydroxyl). It can be obtained by reacting with. For (II), it is possible firstly to use an acid halide (eg L = chlorine) in the presence of a base such as triethylamine or sodium hydroxide. Second, carboxylic acids (L = OH) can also be used, except that coupling reagents such as dicyclohexylcarbodiimide and additives such as 1-hydroxybenzotriazole are used [Chem. Ber. 1970, 788]. Coupling reagents such as 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide, 1,1′-carbonyl-1H-imidazole and similar compounds can also be used. The coupling reagent used to carry out the production method can be any suitable for making an ester or amide bond (eg, Bodansky et al., Peptide Synthesis, 2nd ed., Wiley & Sons). New York, 1976; Gross, Meienhofer, The Peptide: Analysis, Synthesis, Biology (see Academic Press, New York, 1979). Am. Chem. Soc., 1967, 5012] In this method, various chloroformates such as isobutyl chloroformate and isopropyl chloroformate can be used. Similarly, diethyl acetyl chloride, trimethyl acetyl chloride and the like can be used for this purpose.

Scheme 2 (Production of compounds of general formula I-2)

（Ｉ−２）型の本発明の化合物は、図式２に示したように、好適な塩基、例えば水酸化ナトリウムの存在下に一般構造（Ｉ−１）の本発明の化合物を一般構造（ＩＶ）のアルキル化試薬またはアシル化試薬、例えばヨウ化メチルと反応させることで製造することもでき、式（Ｉ−１）、（ＩＶ）および（Ｉ−２）において、
Ｌ^１は塩素、臭素、ヨウ素、トシレートまたはメシレートであり、
Ｒ^３ａはＣ_１−Ｃ_４−アルキルまたはＣ_１−Ｃ_４−アルキルカルボニルである。

As shown in Scheme 2, the compound of the present invention of type (I-2) converts the compound of the present invention of general structure (I-1) into a general structure (IV) in the presence of a suitable base such as sodium hydroxide. ) Can be prepared by reacting with an alkylating reagent or acylating reagent such as methyl iodide, in formulas (I-1), (IV) and (I-2):
L ¹ is chlorine, bromine, iodine, tosylate or mesylate;
R ^3a is C ₁ -C ₄ -alkyl or C ₁ -C ₄ -alkylcarbonyl.

Scheme 3 (Production of compounds of general formula I-3)

式（Ｉ）の化合物は、図式３に示したように２段階プロセスで得ることもでき、式（ＶＩＩ）において、
Ｌ^１は塩素、臭素、ヨウ素またはトリフレートである。

Compounds of formula (I) can also be obtained in a two-step process as shown in Scheme 3, where in formula (VII):
L ¹ is chlorine, bromine, iodine or triflate.

  In a generally known method, an amine of formula (III) is first reacted in this case with an acrylic acid derivative of formula (V) to give an acrylamide of formula (VI). Suitable reaction conditions for this reaction correspond to the reaction conditions specifically described for the reaction of the carboxylic acid derivative of formula (II) in Scheme 1 with the amine of formula (III).

  Next, the compound of the present invention of the formula (I) can be obtained by reacting the acrylamide of the formula (VI) with the halogen compound of the formula (VII) by a literature method in a palladium-catalyzed reaction. For example, the palladium catalyst can be, for example, palladium acetate in the presence of triphenylphosphine (see, eg, Synlett 2006, 18, 2969-2972).

Scheme 4 (Production of compounds of general formulas I-5 and I-6)

式（Ｉ）の化合物は、図式４に示したように、式（Ｉ）の他の化合物から官能基を変換することで得ることもできる。

Compounds of formula (I) can also be obtained by converting functional groups from other compounds of formula (I) as shown in Scheme 4.

  For example, first, a carboxylic acid ester derivative of formula (I-4), which can be synthesized by the method shown in Scheme 1 or 3, is prepared in a manner similar to that generally known in the literature in the presence of a base such as lithium hydroxide. Can be hydrolyzed to give the carboxylic acid of formula (I-5) (see, for example, J. Am. Chem. Soc. 1986, 108, 4603).

  The carboxylic acid of formula (I-5) can then be reacted with an amine of formula (XIII) to give a carboxamide derivative of formula (I-6). Possible reaction conditions for this reaction are specifically illustrated in Scheme 1 for the reaction of a carboxylic acid derivative of formula (II) with an amine of formula (III).

Scheme 5 (Production of compounds of general formulas I-8 and I-9)

式（Ｉ）の他の化合物の官能基の変換による式（Ｉ）の化合物の変換の別の例を図式５に示してある。

Another example of conversion of a compound of formula (I) by conversion of a functional group of another compound of formula (I) is shown in Scheme 5.

  For example, first, a nitrile of formula (I-7), which can be synthesized by the method shown in Scheme 1 or 3, is reduced in a manner generally known in the literature to give an amine of formula (I-8). Can be obtained. Useful reducing agents include, for example, a catalyst such as palladium / carbon (see, for example, J. Am. Chem. Soc. 1928, 50, 3370) or lithium aluminum hydride (see, for example, Org. Reac. 1951, 6) in the presence of hydrogen. , 469). The amine of formula (I-8) can then be reacted with a carboxylic acid derivative of formula (XIV) to give a carboxamide derivative of formula (I-9). The possible reaction conditions for this reaction have already been specifically described in Scheme 1 for the reaction of a carboxylic acid derivative of formula (II) with an amine of formula (III).

Scheme 6 (Production of compounds of general formulas I-11 and I-12)

式（Ｉ）の他の化合物からの官能基の変換による式（Ｉ）の化合物の変換についての別の例を図式６に示してある。

Another example for the conversion of a compound of formula (I) by conversion of a functional group from another compound of formula (I) is shown in Scheme 6.

  First, a nitro compound of formula (I-10), which can be synthesized by the method shown in Scheme 1 or 3, is reduced to an amine of formula (I-11) in a manner generally known in the literature. . Suitable methods for such reduction are in particular metal-mediated reactions, such as tin (II) chloride, iron powder, zinc powder and similar compounds. For example, metal mediated reduction using tin (II) chloride is described in Organic Synthesis Coll. Vol. (III), 453.

  The amine of formula (I-11) can then be reacted with a carboxylic acid derivative of formula (XIV) to give a carboxamide derivative of formula (I-12). Regarding the possible reaction conditions for this reaction, the reaction of a carboxylic acid derivative of formula (II) with an amine of formula (III) has already been specifically described in Scheme 1.

Scheme 6a (Preparation of compounds of general formulas I-13 and I-14)

式（Ｉ）の他の化合物からの官能基の変換による式（Ｉ）の化合物の変換についての別の例を図式６ａに示してある。

Another example for the conversion of a compound of formula (I) by conversion of a functional group from another compound of formula (I) is shown in Scheme 6a.

  First, analogously to methods generally known in the literature, a cyano compound of formula (I-7), which can be synthesized by the method shown in Scheme 1 or 3, is reacted with hydroxylamine to give a compound of formula (I- 13) is obtained.

  The compound of formula (I-13) is then reacted with a carboxylic acid derivative of formula (XIV) such as carbonyl chloride in the presence of a base such as pyridine to give 1,3,3 of formula (I-14). A 4-oxadiazole derivative can be obtained.

Scheme 6b (Preparation of compounds of general formula I-15)

式（Ｉ−１５）のＺ−シンナミド誘導体を、図式６ｂに示した方法に従って得ることができる。

Z-cinnamide derivatives of formula (I-15) can be obtained according to the method shown in Scheme 6b.

  First, a compound of formula (VII) is converted to a compound of formula (XXV) in the presence of a palladium catalyst such as bis (triphenylphosphine) -palladium dichloride and a copper salt such as copper (I) iodide in a generally known manner. To obtain alkanoic acid of formula (XXVI) (Reference: WO2006 / 002981). The amine of formula (III) can then be reacted with a carboxylic acid derivative of formula (XXVI) to give a carboxamide derivative of formula (XXVII). Suitable reaction conditions for this reaction correspond to those specifically described for the reaction of the carboxylic acid derivative of formula (II) with the amine of formula (III) in Scheme 1. The compound of formula (XXVII) can then be reacted with hydrogen in the presence of a suitable catalyst such as Lindlar catalyst to selectively obtain Z-cinnamide of formula (I-15) (eg, Journal of Organic Chemistry 2003, 68, 2913-2920).

Scheme 6c (Preparation of compounds of general formula I-17)

一般式（Ｉ−１７）のＮ−置換されたインドール誘導体を図式６ｃに示した方法に従って得ることができ、この図式において
Ｒ^８ａは水素以外のＲ^８である。

N-substituted indole derivatives of general formula (I-17) can be obtained according to the method shown in Scheme 6c, where R ^8a is R ⁸ other than hydrogen.

  In this method, an indole of general formula (I-16), which can be synthesized by the method shown in Scheme 1, is reacted with a compound of general formula (IVa) in the presence of a base, such as potassium carbonate.

  The carboxylic acid of the general formula (II) in which L is OH is commercially available or known in the literature, and can be synthesized from the literature by a known method.

  For example, formula (IIa):

の桂皮酸誘導体が、例えば一般に公知のブロモ−またはヨードアリール化合物からのヘック反応手順によって、例えば酢酸パラジウムなどの多数のパラジウム触媒の存在下に１−プロペン酸誘導体との反応によって得られる（本明細書においては、次の文献が例として引用される。Ｒｕｓｓｉａｎ Ｊ． Ｏｒｇ． Ｃｈｅｍ １９９５， ３１， ４３９−４４４； Ｓｙｎｔｈ． Ｃｏｍｍｕｎ ２００３， ３３， ３６１−３６５； Ｃｈｉｎｅｓｅ Ｊ． Ｏｒｇ． Ｃｈｅｍ． ２００４， ２４， ５９−６２； Ｓｙｎｔｈｅｓｉｓ １９９７， １９９７， ５２１）。一般に公知のアニリン類を用いることも可能であり、それを最初に例えば亜硝酸ナトリウムなどのジアゾ化試薬の存在下にジアゾニウム塩に変換し、次に酢酸パラジウムなどのパラジウム触媒の存在下に１−プロペン酸誘導体と反応させる（次の文献が、例として本明細書において引用される。Ｅｕｒ． Ｊ． Ｏｒｇ． Ｃｈｅｍ． １９９９， １３５７−１３６６）。式（ＩＩａ）の桂皮酸も、芳香族アルデヒドのマロン酸との反応によって得ることができる（次の文献が、例として本明細書において引用される。Ｏｒｇ． Ｓｙｎｔｈ． １９６３， ＩＶ， ７３１； Ｓｙｎｔｈ． Ｃｏｍｍ． １９９８， ２８ （２０）， ３８１１−１５）。

Of cinnamic acid derivatives are obtained, for example, by reaction with 1-propenoic acid derivatives in the presence of a number of palladium catalysts such as, for example, palladium acetate, eg by generally known Heck reaction procedures from bromo- or iodoaryl compounds (herein The following references are cited as examples in the book: Russian J. Org. Chem 1995, 31, 439-444; Synth. Commun 2003, 33, 361-365, Chinese J. Org. 59-62; Synthesis 1997, 1997, 521). It is also possible to use generally known anilines, which are first converted to a diazonium salt in the presence of a diazotizing reagent such as sodium nitrite and then 1-in the presence of a palladium catalyst such as palladium acetate. React with propenoic acid derivatives (the following references are cited herein as examples: Eur. J. Org. Chem. 1999, 1357-1366). Cinnamic acid of formula (IIa) can also be obtained by reaction of an aromatic aldehyde with malonic acid (the following references are cited herein by way of example: Org. Synth. 1963, IV, 731; Synth Comm. 1998, 28 (20), 3811-15).

  A novel carboxylic acid derivative of general formula II (L = OH) can be obtained, for example, by the following method.

Scheme 7 (Production of compound of general formula II-1)

式（ＩＩ−１）の化合物を図式７に示した方法に従って得ることができ、図式において
アルキルはＣ_１−Ｃ_４−アルキルであり、
Ｌ^２は塩素、臭素、ヨウ素またはトリフレートであり、
Ｌ^３はＨまたはＣ_１−Ｃ_４−アルキルであり、ここで、２個のＬ^３置換基が５員環もしくは６員環を形成していても良い。

The compound of formula (II-1) can be obtained according to the method shown in Scheme 7, wherein alkyl is C ₁ -C ₄ -alkyl,
L ² is chlorine, bromine, iodine or triflate,
L ³ is H or C ₁ -C ₄ -alkyl, wherein two L ³ substituents may form a 5- or 6-membered ring.

  As shown in Scheme 7, the compound of formula (VII) is first reacted here with a boronic acid or boronic ester of formula (XV) in the presence of a palladium catalyst to give a cinnamic acid ester of formula (XVI). Get. The catalyst palladium compound used can be a palladium (II) compound, for example bis (tricyclohexylphosphine) .palladium dichloride (II).

  The carboxylic acid ester of the formula (XVI) is converted to the corresponding cinnamic acid of the formula (II-2) by a generally known method, for example by alkaline hydrolysis with sodium hydroxide as the base, or a C—C cup. It can already be obtained as the free base by changing the reaction conditions (eg temperature or reaction time) during the ring.

Scheme 8 (Production of compound of general formula II-2)

式（ＩＩ−２）の化合物を図式８に示した方法に従って得ることができ、その図式において
Ｌ^４はフッ素、塩素または臭素であり、
Ｙ^１−Ａ^１−Ｈは遊離のＮ−Ｈ官能基を有する置換されていても良いトリアゾール、ピラゾール、テトラゾールまたはイミダゾールであり、有用な置換基はＡもしくはＹの一般的定義で具体的に挙げた基である。

A compound of formula (II-2) can be obtained according to the method shown in Scheme 8, wherein L ⁴ is fluorine, chlorine or bromine,
Y ¹ -A ¹ -H is an optionally substituted triazole, pyrazole, tetrazole or imidazole having a free N—H functional group, and useful substituents are specifically listed in the general definition of A or Y. It is a group.

  Here, in the same manner as in the known method, the aldehyde of the formula (XVII) is first reacted with the heterocycle of the formula (XVIII) in the presence of a base as appropriate, to obtain an aldehyde of the formula (IXX) Some of them are known (see WO2008019760; Tetrahedron (2001), 57 (22), 4781-4785).

  Next, in the same manner as in the literature method, an aldehyde of formula (IXX) is reacted with malonic acid in the presence of a nitrogenous base, for example, piperidine to decinrate the cinnamic acid of formula (II-2). (E.g., Bioorganic & Medicinal Chemistry Letters (2008), 18 (5), 1663-1667; Journal of the Indian Chemical Society (2007), 84 (6), 621-ur, 200-614). ), (6), 364-365).

  Formula (IIb):

ベンゾフランカルボン酸も同様に市販されているか、文献から公知であるか、あるいは文献法によって合成することができる。例としては下記のものなどがある。

Benzofurancarboxylic acids are also commercially available, known from the literature, or can be synthesized by literature methods. Examples include the following:

5-cyano-1-benzofuran-2-carboxylic acid (Liebigs Annalen der Chemie 1982, 10, 1836-1869);
6-Fluoro-1-benzofuran-2-carboxylic acid (US005955495A);
6-fluoro-1-benzofuran-2-carboxylic acid (JP2002 / 201193);
6-cyano-1-benzofuran-2-carboxylic acid (WO2003 / 064411);
6- (trifluoromethyl) -1-benzofuran-2-carboxylic acid (US005955495A);
5-Chloro-6-methyl-1-benzofuran-2-carboxylic acid (WO 2005/080336).

A novel benzofuran carboxylic acid of formula (II-3) can be obtained according to the method shown in Scheme 9, in which L ⁵ is chlorine or bromine,
ALK is _C 1 -C ₄ - alkyl group.

Scheme 9 (Production of compound of general formula II-3)

ここで、公知の方法（例えばＤＥ１０１１５４０８参照）と同様にして、最初に、塩基、例えば炭酸カリウムの存在下に、式（ＸＸ）のヒドロキシアルデヒドを式（ＸＸＩ）のハロ酢酸エチルなどのハロカルボン酸アルキルと反応させて、式（ＸＸＩＩ）のベンゾフランカルボン酸エステルを得る。次に、式（ＸＸＩＩ）のカルボン酸エステルを、一般に公知の方法によって、例えば塩基としての水酸化ナトリウムによるアルカリ性加水分解によって、式（ＩＩ−３）の相当するベンゾフランカルボン酸に変換する。

Here, in a manner similar to known methods (see for example DE10115408), first a hydroxyaldehyde of formula (XX) in the presence of a base, for example potassium carbonate, is converted to an alkyl halocarboxylate such as ethyl haloacetate of formula (XXI). To obtain a benzofuran carboxylate of formula (XXII). The carboxylic acid ester of formula (XXII) is then converted to the corresponding benzofuran carboxylic acid of formula (II-3) by generally known methods, for example by alkaline hydrolysis with sodium hydroxide as base.

  Formula (IIc):

のインドールカルボン酸も同様に市販されているか文献で公知であるか、あるいは文献法によって合成することができる。例としては下記のものなどがある。

These indole carboxylic acids are also commercially available, known in the literature, or can be synthesized by literature methods. Examples include the following:

5-cyano-1H-indole-2-carboxylic acid (J. Org. Chem., 1953, 18, 345-357);
6-cyano-1H-indole-2-carboxylic acid (J. Med. Chem., 1997, 40, 2843-2857);
5- (methylsulfonyl) -1H-indole-2-carboxylic acid (WO2001 / 077101);
5,6-difluoro-1H-indole-2-carboxylic acid (WO 2006/082400);
6-Chloro-1H-pyrrolo [3,2-c] pyridine-2-carboxylic acid (WO 2004/104001).

  A novel indole carboxylic acid of formula (II-4) can be obtained according to the method shown in Scheme 10.

Scheme 10 (Production of compound of general formula II-4)

ここでは、公知の方法（例えばＢｉｏｏｒｇ． Ｍｅｄ． Ｃｈｅｍ． Ｌｅｔｔ． ２００３， １３， ４３８５−４３８８を参照）と同様にして、最初に式（ＸＸＩＩＩ）のアニリンを式（ＸＸＩＶ）のヨードアニリンに変換し、次に酢酸パラジウムおよび塩基、例えば１，４−ジアザビシクロ［２．２．２］オクタンＤＡＢＣＯの存在下にピルビン酸と反応させて、式（ＩＩ−４）のベンゾフランカルボン酸エステルを得る。

Here, the aniline of the formula (XXIII) is first converted to the iodoaniline of the formula (XXIV) in the same manner as in known methods (see, for example, Bioorg. Med. Chem. Lett. 2003, 13, 4385-4388). Subsequent reaction with pyruvic acid in the presence of palladium acetate and a base, for example 1,4-diazabicyclo [2.2.2] octane DABCO, affords the benzofuran carboxylic acid ester of formula (II-4).

  Similarly, a carbonyl halide represented by the general structure (II) (L = halogen), more preferably a carbonyl chloride, a carboxylic acid (L = OH), thionyl chloride, thionyl bromide, phosphoryl chloride, oxalyl chloride, phosphorus trichloride. Can be produced by reacting with a halogenating reagent such as [Houben-Weyl, 1952, vol. VIII, p. 463 ff. ].

  The haloalkyl-substituted amines of general formula (III) are either commercially available or known in the literature or can be synthesized by literature methods. For example, an aryl halide can be reacted with a haloalkyl carboxylate in the presence of magnesium in a Grignard reaction. The ketone so formed can then be converted to the corresponding amine by reductive amination (DE-A-2723464). 2,2,2-trifluoro-1- (pyridin-4-yl) ethanamine is commercially available and is described in Angew. Chem. 1998, 110. 6, 880-881 and J.H. Mol. Cat. B: Can be synthesized in the same manner as in Enzymatic 30 (2004) 61-68.

  The novel haloalkyl-substituted amines of general formula (III) can be obtained, for example, by the following method.

Scheme 10a (Production of compounds of general formula III-1)

式中、
Ｌ^６は−Ｃ_１−Ｃ_４−アルコキシまたは−Ｎ（ＣＨ_３）−Ｏ−Ｃ_１−Ｃ_４−アルキルである。

Where
L ⁶ is —C ₁ -C ₄ -alkoxy or —N (CH ₃ ) —O—C ₁ -C ₄ -alkyl.

  The novel compound of formula (III-1) can be obtained according to the method shown in Scheme 10a. Here, a commercially available or literature compound of formula (IIXXX) can be reacted with a metallizing reagent such as magnesium, Grignard compound, n-butyllithium or tert-butyllithium to give an organometallic intermediate, which is Is reacted with a compound of formula (IXXX) to give a ketone of formula (XXX). This can then be converted to an amine of formula (III-1) by reductive amination in a manner similar to generally known methods. Here, a ketone (XXX) is reacted with, for example, hydroxylamine to form an oxime intermediate, which is then reduced with a reducing agent, such as lithium aluminum hydride, to give an amine of formula (III-1) and To do.

  The (hetaryl) aryl halides of the formula (VII) are known or can be prepared essentially by known methods (for example WO-A-2009055077, EP-A-1445253, EP-A-661258, US). -A-6252090, Chemical & Pharmaceutical Bulletin (1992), 40 (7), 1789-92, Chemical & Pharmaceutical Bulletin (1994), 42 (4), 913-16, Compt. See).

  The novel (hetaryl) aryl halide of the general formula (VII) can be obtained, for example, by the following method.

Scheme 10b (Production of compound of general formula VII-1)

式（ＶＩＩ−１）の新規な化合物は、図式１０ｂに示した方法に従って得ることができる。ここで、市販もしくは文献の式（ＸＸＸＩ）のカルボン酸を式（ＸＩＩＩ）のアミンと反応させることができる。この反応に可能な反応条件については、図式１における式（ＩＩ）のカルボン酸誘導体の式（ＩＩＩ）のアミンとの反応についてすでに具体的に説明している。

The novel compound of formula (VII-1) can be obtained according to the method shown in Scheme 10b. Here, commercially available or literature carboxylic acids of the formula (XXXI) can be reacted with amines of the formula (XIII). Regarding the reaction conditions possible for this reaction, the reaction of the carboxylic acid derivative of formula (II) in Scheme 1 with the amine of formula (III) has already been described in detail.

Scheme 10c (Production of compounds of general formula VII-2)

図式１０ｃに詳細に記載の通り、公知の方法と同様にして、式（ＸＸＸＩＩ）の公知のニトリル誘導体を最初に式（ＸＸＸＩＩＩ）のアルキル−グリニャル試薬と反応させて、式（ＸＸＸＩＶ）のアミンを得る。次に、式（ＸＸＸＩＶ）のアミンを式（ＸＩＶ）のカルボン酸誘導体と反応させて、式（ＶＩＩ−１）のカルボキサミド誘導体を得ることができる。この反応に可能な反応条件については、図式１における式（ＩＩ）のカルボン酸誘導体の式（ＩＩＩ）のアミンとの反応に関してすでに具体的に説明している。

As described in detail in Scheme 10c, a known nitrile derivative of formula (XXXII) is first reacted with an alkyl-Grignard reagent of formula (XXXIII) to give an amine of formula (XXXIV) in a manner similar to known methods. obtain. The amine of formula (XXXIV) can then be reacted with a carboxylic acid derivative of formula (XIV) to give a carboxamide derivative of formula (VII-1). The reaction conditions possible for this reaction have already been specifically described for the reaction of the carboxylic acid derivative of formula (II) in Scheme 1 with the amine of formula (III).

Scheme 10d (Production of compound of general formula VII-3)

図式１０ｄに詳細に記載の通り、公知の方法と同様にして、式（ＸＸＸＶ）のニトリル誘導体を最初に還元剤、例えば水素化リチウムアルミニウムと反応させて、式（ＸＸＸＶＩ）のアミンを得る。次に、式（ＸＸＸＶＩ）のアミンを式（ＸＩＶ）のカルボン酸誘導体と反応させることで、式（ＶＩＩ−３）のカルボキサミド誘導体を得ることができる。この反応に可能な反応条件については、図式１における式（ＩＩ）のカルボン酸誘導体の式（ＩＩＩ）のアミンとの反応に関してすでに具体的に説明している。

A nitrile derivative of formula (XXXV) is first reacted with a reducing agent, such as lithium aluminum hydride, to give an amine of formula (XXXVI), as described in detail in Scheme 10d, in a manner similar to known methods. Next, the carboxamide derivative of the formula (VII-3) can be obtained by reacting the amine of the formula (XXXVI) with the carboxylic acid derivative of the formula (XIV). The reaction conditions possible for this reaction have already been specifically described for the reaction of the carboxylic acid derivative of formula (II) in Scheme 1 with the amine of formula (III).

Scheme 10e (Production of compound of general formula VII-4)

図式１０ｄに詳細に記載の通り、公知の方法と同様にして、塩基、例えば水素化ナトリウムの存在下に、式（ＸＸＸＶＩＩ）のハロゲン誘導体を式（ＸＸＸＶＩＩＩ）のＢｏｃ保護されたアミンと反応させる。次に、保護基を脱離させて、式（ＶＩＩ−４）の二級アミンを得る。

As described in detail in Scheme 10d, a halogen derivative of formula (XXXVII) is reacted with a Boc protected amine of formula (XXXVIII) in the presence of a base, such as sodium hydride, in a manner similar to known methods. The protecting group is then removed to give the secondary amine of formula (VII-4).

  Carboxylic acids of general formula (II) in which L is OH are either commercially available or known from the literature or can be synthesized by literature methods (Schemes 7 to 10). Production of carbonyl halides of general formula (II), where L is halogen, is described after Scheme 10.

  Formula (IV), (IVa), (V), (XIII), (XIV), (XV), (XVII), (XVIII), (XX), (XXI), (XXIII), (XXV), (XXV) The compounds of IIXXX), (XXX), (XXXI), (XXXII), (XXXIII), (XXXVI), (XXXVII) and (XXXVIII) are known materials in the literature or are commercially available.

  Compounds of general formula I-1, I-2, I-4, I-7 and I-10 can be obtained according to scheme 1, and compounds of general formula II-1 can be obtained according to scheme 7.

  The process according to the invention for preparing the novel compounds of formula (I) is preferably carried out using a diluent. Diluents useful in carrying out the process according to the invention can be all inert solvents in addition to water. Examples include halohydrocarbons (eg tetrachloroethylene, tetrachloroethane, dichloropropane, methylene chloride, dichlorobutane, chloroform, carbon tetrachloride, trichloroethane, trichloroethylene, pentachloroethane, difluorobenzene, 1,2-dichloroethane, chlorobenzene, bromobenzene. , Chlorobenzenes such as dichlorobenzene, chlorotoluene, and trichlorobenzene), alcohols (eg, methanol, ethanol, isopropanol, butanol), ethers (eg, ethylpropyl ether, methyl tert-butyl ether, n-butyl ether, anisole, Phenetol, cyclohexyl methyl ether, dimethyl ether, diethyl ether, dipropyl ether, diisopropyl ether, di n-butyl ether, diisobutyl ether, diisoamyl ether, ethylene glycol dimethyl ether, tetrahydrofuran, dioxane, dichlorodiethyl ether and polyethers of ethylene oxide and / or propylene oxide), amines (eg, trimethyl-, triethyl-, tripropyl-, Tributylamine, N-methylmorpholine, pyridine and tetramethylenediamine), nitro hydrocarbons (eg nitromethane, nitroethane, nitropropane, nitrobenzene, chloronitrobenzene, o-nitrotoluene; acetonitrile, propionitrile, butyronitrile, isobutyronitrile, Nitriles such as benzonitrile and m-chlorobenzonitrile), tetrahydrothiophene dioxide, dimethyl Sulfoxide, tetramethylene sulfoxide, dipropyl sulfoxide, benzylmethyl sulfoxide, diisobutyl sulfoxide, dibutyl sulfoxide, diisoamyl sulfoxide, sulfones (eg dimethyl, diethyl, dipropyl, dibutyl, diphenyl, dihexyl, methylethyl, ethylpropyl, ethylisobutyl and Pentamethylene sulfone), aliphatic, cycloaliphatic or aromatic hydrocarbons (eg, pentane, hexane, heptane, octane, nonane and industrial hydrocarbons) and components having boiling points in the range of 40 ° C to 250 ° C, for example. Volatile oil containing, cymene, petroleum fraction within the boiling range of 70 ° C to 190 ° C, cyclohexane, methylcyclohexane, petroleum ether, ligroin, octane, benzene, toluene, chloro Benzene, bromobenzene, nitrobenzene, xylene, esters (eg, methyl acetate, ethyl, butyl, isobutyl, dimethyl carbonate, dibutyl, ethylene); amides (eg, hexamethylene phosphoramide, formamide, N-methylformamide, N , N-dimethylformamide, N, N-dipropylformamide, N, N-dibutylformamide, N-methylpyrrolidine, N-methylcaprolactam, 1,3-dimethyl-3,4,5,6-tetrahydro-2 (1H ) -Pyrimidine, octylpyrrolidone, octylcaprolactam, 1,3-dimethyl-2-imidazolinedione, N-formylpiperidine, N, N'-1,4-diformylpiperidine) and ketones (eg acetone, acetophenone, methyl ethyl ketone) , Methyl butyl Tons).

  It will be clear that the process according to the invention can also be carried out in the mixtures of solvents and diluents mentioned.

  When carrying out the process according to the invention, the reaction temperatures can be varied within a relatively wide range. In general, the temperatures used are -30 ° C to + 150 ° C, preferably -10 ° C to + 100 ° C.

  The process according to the invention is usually carried out under standard pressure. However, it is also possible to carry out the process according to the invention under high pressure or reduced pressure, usually at an absolute pressure of 0.01 MPa to 1.5 MPa (0.1 bar to 15 bar).

  To carry out the process according to the invention, the starting materials are used in approximately equimolar amounts. However, it is also possible to use one of the components in a relatively large excess. The reaction is usually carried out in a suitable diluent in the presence of a reaction auxiliary, optionally under a protective gas atmosphere (eg under nitrogen, argon or helium) and the reaction mixture is usually at the required temperature for several hours. Over stirring. Post-processing is performed by a general method (refer to a manufacturing example).

  The basic reaction aids used to carry out the process according to the invention can be all suitable acid binders. Examples include alkaline earth metals or alkali metal compounds (eg, hydroxides, hydrides, oxides and carbonates of lithium, sodium, potassium, magnesium, calcium and barium), amidine bases or guanidine bases (eg 7 -Methyl-1,5,7-triaza-bicyclo (4.4.0) dec-5-ene (MTBD); diazabicyclo (4.3.0) nonene (DBN), diazabicyclo (2.2.2) octane (DABCO), 1,8-diazabicyclo (5.4.0) undecene (DBU), cyclohexyltetrabutylguanidine (CyTBG), cyclohexyltetramethylguanidine (CyTMG), N, N, N, N-tetramethyl-1, 8-naphthalenediamine, pentamethylpiperidine) and amines, especially tertiary amino acids (E.g., triethylamine, trimethylamine, tribenzylamine, triisopropylamine, tributylamine, tricyclohexylamine, triamylamine, trihexylamine, N, N-dimethylaniline, N, N-dimethyltoluidine, N, N-dimethyl -P-aminopyridine, N-methyl-pyrrolidine, N-methylpiperidine, N-methylimidazole, N-methylpyrazole, N-methylmorpholine, N-methylhexamethylenediamine, pyridine, 4-pyrrolidinopyridine, 4-dimethyl Aminopyridine, quinoline, α-picoline, β-picoline, pyrimidine, acridine, N, N, N ′, N′-tetramethylenediamine, N, N, N ′, N′-tetraethylenediamine, quinoxaline, N-propyldiisopropyl Ami , N- ethyl - diisopropylamine, N, N'-dimethylcyclohexylamine, 2,6-lutidine, 2,4-lutidine or triethyl diamine), and the like.

  The acidic reaction aids used to carry out the process according to the invention are all mineral acids (eg hydrohalic acids such as hydrofluoric acid, hydrochloric acid, hydrobromic acid or hydroiodic acid and sulfuric acid, phosphoric acid). , Phosphorous acid, nitric acid), Lewis acids (eg, aluminum (III) chloride, boron trifluoride or their etherates, titanium (V), tin (V) chloride and organic acids (eg, formic acid, acetic acid, propion) It can be acid, malonic acid, lactic acid, oxalic acid, fumaric acid, adipic acid, stearic acid, tartaric acid, oleic acid, methanesulfonic acid, benzoic acid, benzenesulfonic acid or paratoluenesulfonic acid.

  Schemes 11 to 21 show, by way of example, the preparation of specific preferred compounds of the invention of general formula I.

Scheme 11

Scheme 11a

Scheme 12

Schematic 12a

Schematic 12b

Schematic 12c

Schematic 12d

Scheme 13

Scheme 14

Scheme 15

Scheme 16

Scheme 17

Scheme 18

Scheme 19

Scheme 20

Scheme 21

下記の製造例および使用例によって本発明を説明するが、これらは本発明を限定するものではない。

The following production examples and use examples illustrate the present invention, but are not intended to limit the present invention.

Production Examples In the following examples, RT means room temperature, ie 20 ° C., and the expression “1 eq” means 1 equivalent.

Synthesis Example 1 (Production of compounds of general formulas I-1 and I-2 according to Schemes 1 and 2)
Stage 1
(2E) -3- (4-Cyanophenyl) -N- {2,2,2-trifluoro-1- [3- (trifluoromethyl) phenyl] ethyl} acrylamide (Compound No. Ia-8 in Table 1) )

２，２−トリフルオロ−１−［３−（トリフルオロメチル）フェニル］エタンアミン（ＤＥ−Ａ−２７２３４６４から公知）２８０．８ｍｇ（１．１５ｍｍｏｌ）およびトリエチルアミン１２８．６ｍｇ（１．２７ｍｍｏｌ）を最初にジクロロメタン２ｍＬ中に入れ、（２Ｅ）−３−（４−シアノフェニル）アクリロイルクロライド（（２Ｅ）−３−（４−シアノフェニル）アクリル酸のオキサリルクロライドとの反応によって合成）の溶液２２１．３ｍｇ（１．１５ｍｍｏｌ）を加えた。反応溶液を室温で１８時間撹拌し、ジクロロメタンで希釈し、水で３回洗浄し、硫酸ナトリウムで脱水した。溶媒を減圧下に留去し、残留物をジイソプロピルエーテルとともに撹拌した。

280.8 mg (1.15 mmol) of 2,2-trifluoro-1- [3- (trifluoromethyl) phenyl] ethanamine (known from DE-A-2723464) and 128.6 mg (1.27 mmol) of triethylamine first 221.3 mg of a solution of (2E) -3- (4-cyanophenyl) acryloyl chloride (synthesized by reaction of (2E) -3- (4-cyanophenyl) acrylic acid with oxalyl chloride) in 2 mL of dichloromethane ( 1.15 mmol) was added. The reaction solution was stirred at room temperature for 18 hours, diluted with dichloromethane, washed 3 times with water, and dried over sodium sulfate. The solvent was distilled off under reduced pressure and the residue was stirred with diisopropyl ether.

  Yield: 280 mg (59.4% of theory).

¹ H NMR (400 MHz, d ₆ -DMSO) δ = 6.09 (m, 1H), 6.95 (d, 1H), 7.6 (d, 1H), 7.7 (m, 1H), 7 .75 (m, 3H), 7.85 (m, 2H), 7.89 (m, 1H), 7.99 (m, 1H), 9.42 (d, 1H).

HPLC-MS: log P = 3.54; mass (m / z): 399.0 (M + H) ^<+> .

Stage 2
(2E) -3- (4-Cyanophenyl) -N-methyl-N- {2,2,2-trifluoro-1- [3- (trifluoromethyl) phenyl] -ethyl} acrylamide (in Table 1 Compound No. Ia-25)

合成例１段階１からの（２Ｅ）−３−（４−シアノフェニル）−Ｎ−｛２，２，２−トリフルオロ−１−［３−（トリフルオロメチル）−フェニル］エチル｝アクリルアミド１２０．０ｍｇ（０．３０ｍｍｏｌ）を最初に、Ｎ，Ｎ−ジメチルホルムアミド２ｍＬに入れ、０℃で水素化ナトリウム（５５％オイル中分散品）１９．７ｍｇ（０．４５ｍｍｏｌ）を混合した。ヨウ化メチル６４．１ｍｇ（０．４５ｍｍｏｌ）を加えた後、混合物を室温で１８時間撹拌した。反応混合物を酢酸エチルで希釈し、水で３回洗浄し、硫酸ナトリウムで脱水した。溶媒を減圧下に留去し、残留物を分取ＨＰＬＣによって精製した（溶媒＝水（Ａ）＋アセトニトリル（Ｂ）、勾配＝４０分で１０％Ｂから１００％Ｂ、流量＝１８ｍＬ／分）。

Synthesis Example 1 (2E) -3- (4-Cyanophenyl) -N- {2,2,2-trifluoro-1- [3- (trifluoromethyl) -phenyl] ethyl} acrylamide 120 from step 1. First, 0 mg (0.30 mmol) was placed in 2 mL of N, N-dimethylformamide, and 19.7 mg (0.45 mmol) of sodium hydride (55% dispersion in oil) was mixed at 0 ° C. After adding 64.1 mg (0.45 mmol) of methyl iodide, the mixture was stirred at room temperature for 18 hours. The reaction mixture was diluted with ethyl acetate, washed 3 times with water and dried over sodium sulfate. The solvent was removed under reduced pressure and the residue was purified by preparative HPLC (solvent = water (A) + acetonitrile (B), gradient = 10% B to 100% B in 40 minutes, flow rate = 18 mL / min). .

  Yield: 32 mg (25% of theory).

¹ H NMR (400 MHz, d ₃ -acetonitrile) δ = 3.00 (s, 3H), 6.75 (brm, 1H), 7.20 (d, 1H), 7.6-7.8 (m, 9H).

HPLC-MS: log P = 4.01; mass (m / z): 413.0 (M + H) ^<+> .

  Further compounds of the general formula (I) obtained in the same manner as in Synthesis Example 1 are listed in Tables 1 and 2.

Synthesis Example 2 (General formula for the preparation of compounds of I-3, I-5 and I-6 according to Schemes 3 and 4)
Stage 1
N- {2,2,2-trifluoro-1- [3- (trifluoromethyl) phenyl] ethyl} acrylamide

２，２−トリフルオロ−１−［３−（トリフルオロメチル）フェニル］エタンアミン（文献：ＤＥ２７２３４６４）２０．０ｇ（８２．２ｍｍｏｌ）を最初に、ピリジン７．８０ｇ（９８．７ｍｍｏｌ）とともにジクロロメタン５００ｍＬに入れ、アクリロイルクロライド７．４４ｇ（８２．２ｍｍｏｌ）をそれに０℃で滴下した。反応混合物をさらに４時間撹拌しながら、昇温させて室温とした。その後、混合物を水で繰り返し洗浄し水、有機相を硫酸ナトリウムで脱水し、溶媒を減圧下に留去した。生成物をそれ以上精製せずに、段階２で用いた。

20.0 g (82.2 mmol) of 2,2-trifluoro-1- [3- (trifluoromethyl) phenyl] ethanamine (literature: DE2723464) was first added to 500 mL of dichloromethane together with 7.80 g (98.7 mmol) of pyridine. Then, 7.44 g (82.2 mmol) of acryloyl chloride was added dropwise thereto at 0 ° C. The reaction mixture was allowed to warm to room temperature while stirring for an additional 4 hours. Thereafter, the mixture was washed repeatedly with water, water, the organic phase was dehydrated with sodium sulfate, and the solvent was distilled off under reduced pressure. The product was used in step 2 without further purification.

  Yield: 14.2 g (44.6% of theory).

¹ H NMR (400 MHz, d ₆ -DMSO) δ = 5.77 (m, 1H), 6.12 (m, 1H), 6.20 (m, 1H), 6.42 (m, 1H), 7 .70 (m, 2H), 7.79 (m, 1H), 7.92 (m, 1H), 8.02 (s, 1H), 9.41 (d, 1H).

HPLC-MS: log P = 2.75; mass (m / z): 298.0 (M + H) ^<+> .

Stage 2
4-[(1E) -3-oxo-3-({2,2,2-trifluoro-1- [3- (trifluoromethyl) phenyl] ethyl} amino) prop-1-en-1-yl] -2- (Trifluoromethyl) benzoic acid

アルゴン下に、最初に実施例２段階１からのＮ−｛２，２，２−トリフルオロ−１−［３−（トリフルオロメチル）フェニル］エチル｝−アクリルアミド１３．３４ｇ（７．９０ｍｍｏｌ）と次に４−ヨード−２−（トリフルオロメチル）安息香酸（市販品、ＣＡＳ登録番号９５４８１５−１１−３）２．４９ｇ（７．９０ｍｍｏｌ）、トリフェニルホスフィン０．２０６ｇ（７．９０ｍｍｏｌ）、酢酸パラジウム（ＩＩ）８８．４ｍｇ（０．３９ｍｍｏｌ）およびトリエチルアミン１３．５ｇ（１３３ｍｍｏｌ）を最初に、Ｎ，Ｎ−ジメチルホルムアミド６７ｍＬに入れ、反応混合物を１００℃で５時間撹拌した。水を加えた後、溶液を酢酸エチルで抽出し、有機相を飽和塩化ナトリウム溶液で３回洗浄し、硫酸ナトリウムで脱水した。溶媒を減圧下に留去し、残留物について、酢酸エチルを用いるシリカゲルでのクロマトグラフィーを行った。

Under argon, initially 13.34 g (7.90 mmol) of N- {2,2,2-trifluoro-1- [3- (trifluoromethyl) phenyl] ethyl} -acrylamide from Example 2 Step 1 Next, 4-iodo-2- (trifluoromethyl) benzoic acid (commercial product, CAS Registry Number 954815-11-3) 2.49 g (7.90 mmol), triphenylphosphine 0.206 g (7.90 mmol), acetic acid Palladium (II) 88.4 mg (0.39 mmol) and triethylamine 13.5 g (133 mmol) were initially placed in 67 mL of N, N-dimethylformamide and the reaction mixture was stirred at 100 ° C. for 5 hours. After adding water, the solution was extracted with ethyl acetate and the organic phase was washed three times with saturated sodium chloride solution and dried over sodium sulfate. The solvent was removed under reduced pressure and the residue was chromatographed on silica gel using ethyl acetate.

  Yield: 2.57 g (60% of theory).

¹ H NMR (400 MHz, d ₆ -DMSO) δ = 6.10 (m, 1H), 6.93 (d, 1H), 7.6 (m, 1H), 7.69 (m, 1H), 7 .75 (m, 2H), 7.85 (m, 1H), 7.95 (m, 1H), 7.99 (m, 1H), 9.38 (d, 1H).

HPLC-MS: log P = 3.29; mass (m / z): 486.0 (M + H) ^<+> .

  In the same manner as in the method described in Synthesis Example 2 Step 2, a compound of the following general formula (I-5) was also obtained.

2-Methyl-4-[(1E) -3-oxo-3-({2,2,2-trifluoro-1- [3- (trifluoromethyl) phenyl] ethyl} amino) prop-1-ene- 1-yl] benzoic acid
¹ H NMR (400 MHz, d ₆ -DMSO) δ = 2.55 (s, 3H), 6.09 (m, 1H), 6.89 (d, 1H), 7.6 (m, 1H), 7 .50 (m, 3H), 7.7-7.9 (m, 3H), 8.00 (m, 1H), 9.34 (d, 1H).

HPLC-MS: log P = 3.14; mass (m / z): 431.1 (M + H) ^<+> .

2-Chloro-4-[(1E) -3-oxo-3-({2,2,2-trifluoro-1- [3- (trifluoromethyl) phenyl] ethyl} amino) prop-1-ene- 1-yl] benzoic acid
¹ H NMR (400 MHz, d ₆ -DMSO) δ = 6.09 (m, 1H), 6.90 (d, 1H), 7.6 (m, 1H), 7.50 (m, 1H), 7 .60 (m, 1H), 7.71 (m, 1H), 7.79 (m, 1H), 7.90 (m, 1H), 8.00 (s, 1H), 9.37 (d, 1H).

HPLC-MS: log P = 3.10; mass (m / z): 452.0 (M + H) ^<+> .

2-Bromo-4-[(1E) -3-oxo-3-({2,2,2-trifluoro-1- [3- (trifluoromethyl) phenyl] ethyl} amino) prop-1-ene- 1-yl] benzoic acid
¹ H NMR (400 MHz, d ₆ -DMSO) δ = 6.09 (m, 1H), 6.91 (d, 1H), 7.6 (m, 1H), 7.50 (d, 1H), 7 .62 (m, 1H), 7.70 (m, 2H), 7.79 (m, 1H), 7.90 (m, 1H), 7.99 (m, 1H), 9.36 (d, 1H).

HPLC-MS: log P = 3.15; mass (m / z): 496.0 (M + H) ^<+> .

Stage 3
N- (1-fluoropropan-2-yl) -4-[(1E) -3-oxo-3-({2,2,2-trifluoro-1- [3- (trifluoromethyl) phenyl]- Ethyl} amino) prop-1-en-1-yl] -2- (trifluoromethyl) benzamide (Compound No. Ia-75 in Table 1)

実施例２段階２からの４−［（１Ｅ）−３−オキソ−３−（｛２，２，２−トリフルオロ−１−［３−（トリフルオロメチル）フェニル］エチル｝−アミノ）プロプ−１−エン−１−イル］−２−（トリフルオロメチル）安息香酸４９ｍｇ（１当量、０．１ｍｍｏｌ）をジクロロメタン１ｍＬに溶かした。次に、６−クロロヒドロキシベンゾトリアゾール１７ｍｇ（１．０当量、０．１０ｍｍｏｌ）、Ｎ−（３−ジメチルアミノプロピル）−Ｎ′−エチルカルボジイミド塩酸塩２３ｍｇ（１．２当量、０．１２ｍｍｏｌ）およびＮ−エチルジイソプロピルアミン２６ｍｇ（２当量、０．２０ｍｍｏｌ）をそれに加え、混合物をＲＴで２０分間撹拌した。次に、１−フルオロプロパン−２−アミン塩酸塩１１ｍｇ（１．０当量、０．１０ｍｍｏｌ）を加え、反応混合物を室温で１２時間撹拌した。その後、反応混合物を濃縮し、得られた粗生成物を分取ＨＰＬＣ（ｐｈｅｎｏｍｅｎｅｘ Ｇｅｍｉｎｉ Ｃ１８ ５μｍ；１１０Ａ；ＡＸＩＡ ５０×２１．２ｍｍ；勾配：０から２分：７０％水、３０％ＭｅＯＨ、２．５から６．０分：５％水、９５％ＭｅＯＨまでの直線勾配、６．０から２０．００分：５％水、９５％ＭｅＯＨ；調整剤：２０％ＨＣＯＯＨを２ｍＬ／分で添加）によって精製した。これによって、Ｎ−（１−フルオロプロパン−２−イル）−４−［（１Ｅ）−３−オキソ−３−（｛２，２，２−トリフルオロ−１−［３−（トリフルオロメチル）フェニル］エチル｝アミノ）−プロプ−１−エン−１−イル］−２−（トリフルオロメチル）ベンズアミド２７ｍｇ（３７％）が固体として得られる。

Example 2 4-[(1E) -3-oxo-3-({2,2,2-trifluoro-1- [3- (trifluoromethyl) phenyl] ethyl} -amino) prop- from step 2 1-en-1-yl] -2- (trifluoromethyl) benzoic acid 49 mg (1 equivalent, 0.1 mmol) was dissolved in 1 mL of dichloromethane. Next, 17 mg (1.0 eq, 0.10 mmol) of 6-chlorohydroxybenzotriazole, 23 mg (1.2 eq, 0.12 mmol) of N- (3-dimethylaminopropyl) -N′-ethylcarbodiimide hydrochloride and N-ethyldiisopropylamine 26 mg (2 eq, 0.20 mmol) was added to it and the mixture was stirred at RT for 20 min. Next, 11 mg (1.0 eq, 0.10 mmol) of 1-fluoropropan-2-amine hydrochloride was added and the reaction mixture was stirred at room temperature for 12 hours. The reaction mixture is then concentrated and the resulting crude product is purified by preparative HPLC (phenomenex Gemini C18 5 μm; 110A; AXIA 50 × 21.2 mm; gradient: 0 to 2 minutes: 70% water, 30% MeOH; 5 to 6.0 min: 5% water, linear gradient from 95% MeOH, 6.0 to 20.00 min: 5% water, 95% MeOH; modifier: 20% HCOOH added at 2 mL / min) Purified. This produced N- (1-fluoropropan-2-yl) -4-[(1E) -3-oxo-3-({2,2,2-trifluoro-1- [3- (trifluoromethyl) 27 mg (37%) of phenyl] ethyl} amino) -prop-1-en-1-yl] -2- (trifluoromethyl) benzamide are obtained as a solid.

HPLC-MS: log P = 3.37, mass (m / z): 544.96 (M + H) ^<+> .

¹ H NMR (400 MHz, d6-DMSO): δ = 9.51 (d, 1H), 8.60 (d, 1H), 8.05 (s, 1H), 8.00 (s, 1H), 7 .95 (m, 2H), 7.80 (d, 1H), 7.72 (t, 1H), 7.66 (d, 1H, J = 16 Hz), 7.55 (d, 1H), 6. 96 (d, 1 H, J = 16 Hz), 6.17 (m, 1 H), 4.38 (dd, 2 H, 1 J (H, F) = 47 Hz and J (H, H) = 5 Hz), 4.20 (M, 1H), 1.15 (d, 3H).

Synthesis Example 3 (Production of compounds of general formulas I-11 and I-12 according to scheme 6)
Stage 1
(2E) -3- (3-Nitrophenyl) -N- {2,2,2-trifluoro-1- [3- (trifluoromethyl) phenyl] ethyl} acrylamide

２，２−トリフルオロ−１−［３−（トリフルオロメチル）フェニル］エタンアミン（文献：ＤＥ２７２３４６４）３００ｍｇ（１．２３ｍｍｏｌ）およびトリエチルアミン１３７ｍｇ（１．３５ｍｍｏｌ）を最初に、ジクロロメタン２ｍＬに入れ、（２Ｅ）−３−（３−ニトロフェニル）アクリロイルクロライド２６１ｍｇ（１．２３ｍｍｏｌ）の溶液（（２Ｅ）−３−（３−ニトロフェニル）アクリル酸のオキサリルクロライドとの反応による合成）を加えた。反応溶液を室温で１８時間撹拌し、ジクロロメタンで希釈し、水で３回洗浄し、硫酸ナトリウムで脱水した。溶媒を減圧下に留去し、残留物をジイソプロピルエーテルとともに撹拌した。

300 mg (1.23 mmol) of 2,2-trifluoro-1- [3- (trifluoromethyl) phenyl] ethanamine (literature: DE 2723464) and 137 mg (1.35 mmol) of triethylamine are initially placed in 2 mL of dichloromethane (2E A solution of 261 mg (1.23 mmol) of) -3- (3-nitrophenyl) acryloyl chloride (synthesis by reaction of (2E) -3- (3-nitrophenyl) acrylic acid with oxalyl chloride) was added. The reaction solution was stirred at room temperature for 18 hours, diluted with dichloromethane, washed 3 times with water, and dried over sodium sulfate. The solvent was distilled off under reduced pressure and the residue was stirred with diisopropyl ether.

  Yield: 417 mg (69.5% of theory).

¹ H NMR (400 MHz, d ₆ -DMSO) δ = 6.10 (m, 1H), 7.00 (d, 1H), 7.6 (d, 1H), 7.75 (m, 1H), 7 .8 (m, 3H), 7.85 (m, 2H), 7.89 (m, 1H), 7.99 (m, 1H), 9.43 (d, 1H).

HPLC-MS: log P = 3.81; mass (m / z): 419.1 (M + H) ^<+> .

Stage 2
(2E) -3- (3-Aminophenyl) -N- {2,2,2-trifluoro-1- [3- (trifluoromethyl) phenyl] ethyl} acrylamide

Ｓｎ（ＩＩ）Ｃｌ_２６２６ｍｇ（３．３０ｍｍｏｌ）を最初に、エタノール５ｍＬに入れ、実施例３段階１からの（２Ｅ）−３−（３−ニトロフェニル）−Ｎ−｛２，２，２−トリフルオロ−１−［３−（トリフルオロメチル）フェニル］エチル｝−アクリルアミド３５０ｍｇ（０．８３ｍｍｏｌ）を加えた。反応溶液を還流温度で１時間撹拌し、冷却し、水５０ｍＬと混合した。氷で冷却しながら、濃水酸化ナトリウム溶液でｐＨを９に調節し、混合物をジクロロメタンで抽出した。有機相を硫酸ナトリウムで脱水し、溶媒を減圧下に留去し、残留物をジイソプロピルエーテルとともに撹拌した。

First, 626 mg (3.30 mmol) of Sn (II) Cl ₂ was placed in 5 mL of ethanol and (2E) -3- (3-nitrophenyl) -N- {2,2,2- 350 mg (0.83 mmol) of trifluoro-1- [3- (trifluoromethyl) phenyl] ethyl} -acrylamide was added. The reaction solution was stirred at reflux temperature for 1 hour, cooled and mixed with 50 mL of water. While cooling with ice, the pH was adjusted to 9 with concentrated sodium hydroxide solution and the mixture was extracted with dichloromethane. The organic phase was dehydrated with sodium sulfate, the solvent was distilled off under reduced pressure and the residue was stirred with diisopropyl ether.

  Yield: 279 mg (74.6% of theory).

¹ H NMR (400 MHz, d ₆ -DMSO) δ = 6.08 (m, 1H), 6.65 (m, 1H), 7.6 (d, 1H), 7.75 (m, 1H), 7 .04 (m, 1H), 7.38 (m, 1H), 7.68 (m, 1H), 7.75 (m, 1H), 7.90 (m, 1H), 7.99 (m, 1H), 9.25 (m, 1H).

HPLC-MS: log P = 2.88; mass (m / z): 389.1 (M + H) ^<+> .

Stage 3
2-Chloro-N- {3-[(1E) -3-oxo-3-({2,2,2-trifluoro-1- [3- (trifluoromethyl) phenyl] ethyl} amino) prop-1 -En-1-yl] phenyl} nicotinamide (Compound Ia-5 in Table 1)

実施例３段階２からの（２Ｅ）−３−（３−アミノフェニル）−Ｎ−｛２，２，２−トリフルオロ−１−［３−（トリフルオロメチル）フェニル］−エチル｝アクリルアミド１００ｍｇ（０．２５ｍｍｏｌ）およびトリエチルアミン３３．８ｍｇ（０．３３ｍｍｏｌ）を最初に、トリクロロメタン１ｍＬに入れ、２−クロロニコチニルクロライド４９．８ｍｇ（０．３３ｍｍｏｌ）のトリクロロメタン（１ｍＬ）中溶液を加えた。反応溶液を室温で１８時間撹拌し、ジクロロメタンで希釈し、水で３回洗浄し、硫酸ナトリウムで脱水した。溶媒を減圧下に留去し、残留物をし分取ＨＰＬＣ（溶媒＝水（Ａ）＋アセトニトリル（Ｂ）、勾配＝４０分かけて１０％Ｂから１００％Ｂ、流量＝１８ｍＬ／分）によって精製た。

Example 3 100 mg of (2E) -3- (3-aminophenyl) -N- {2,2,2-trifluoro-1- [3- (trifluoromethyl) phenyl] -ethyl} acrylamide from Step 2 0.25 mmol) and 33.8 mg (0.33 mmol) of triethylamine were first taken up in 1 mL of trichloromethane and a solution of 49.8 mg (0.33 mmol) of 2-chloronicotinyl chloride in trichloromethane (1 mL) was added. The reaction solution was stirred at room temperature for 18 hours, diluted with dichloromethane, washed 3 times with water, and dried over sodium sulfate. The solvent was distilled off under reduced pressure and the residue was removed by preparative HPLC (solvent = water (A) + acetonitrile (B), gradient = 10% B to 100% B over 40 minutes, flow rate = 18 mL / min). Purified.

  Yield: 80.0 mg (58.9% of theory).

¹ H NMR (400 MHz, d ₆ -DMSO) δ = 6.08 (m, 1H), 6.83 (d, 1H), 7.36 (m, 1H), 7.40 (m, 1H), 7 .52 (m, 2H), 7.72 (m, 1H), 7.75 (m, 1H), 7.89 (m, 1H), 7.99 (m, 1H), 8.05 (m, 1H), 8.12 (m, 1H), 8.52 (m, 1H), 9.38 (m, 1H).

HPLC-MS: log P = 3.39; mass (m / z): 528.1 (M + H) ^<+> .

Synthesis Example 4 (Production of compounds of general formulas I-1 and II-1 according to schemes 1 and 7)
Stage 1
1- [3-Chloro-5- (trifluoromethyl) phenyl] -2,2,2-trifluoroethanamine

低温温度計、滴下漏斗およびアルゴン風船を取り付けた５００ｍＬ多頸フラスコ中、マグネシウム削片５．５ｇ（０．２２８ｍｏｌ、１．３当量）（ジブロモエタンで活性化し、ジエチルエーテルで洗浄）をジエチルエーテル１２０ｍＬで覆った。０℃で、ジエチルエーテル１２０ｍＬ中の３−ブロモ−５−クロロベンゾトリフルオリド（０．１７５ｍｏｌ、１当量）４５．５ｇをゆっくり滴下した。反応が数分後に自発的に開始し、色が変化し（赤−褐色）、昇温し、添加中は温度を約０℃に維持した。臭化物の添加完了した時点で、混合物をさらに３０分間撹拌した。

In a 500 mL multi-necked flask equipped with a cryogenic thermometer, dropping funnel and argon balloon, 5.5 g (0.228 mol, 1.3 eq) of magnesium chips (activated with dibromoethane and washed with diethyl ether) in 120 mL of diethyl ether Covered with. At 0 ° C., 45.5 g of 3-bromo-5-chlorobenzotrifluoride (0.175 mol, 1 equivalent) in 120 mL of diethyl ether was slowly added dropwise. The reaction started spontaneously after a few minutes, the color changed (red-brown), warmed, and the temperature was maintained at about 0 ° C. during the addition. When the bromide addition was complete, the mixture was stirred for an additional 30 minutes.

  In a separate 2 liter three-necked flask equipped with a cryogenic thermometer, dropping funnel and argon balloon, first put 32.4 g of ethyl trifluoroacetate (0.228 mol, 1.3 eq) in 250 mL of diethyl ether and allow to cool. It was set to −80 ° C. At this temperature, Grignard reagent (cooled to −10 ° C.) was slowly added dropwise. When the addition was complete, the reaction mixture was stirred at −80 ° C. for an additional 30 minutes. The reaction mixture was then warmed to -10 ° C and acidified with 10% hydrochloric acid. The resulting mixture was mixed with saturated NaCl solution, the phases were separated, and the aqueous phase was washed with 200 to 300 mL of diethyl ether. The combined ether phases were dehydrated with magnesium sulfate and then the solvent was removed on a rotary evaporator.

  The resulting crude product was purified by vacuum drying (71 ° C./1.8 kPa (18 mbar)). There were obtained 37.7 g (78% of theory) of 1- [3-chloro-5- (trifluoromethyl) phenyl] -2,2,2-trifluoroethanone as a colorless oil. This was converted without further purification.

To a solution of 24.5 g (88 mmol, 1 eq) of 1- [3-chloro-5- (trifluoromethyl) phenyl] -2,2,2-trifluoroethanone in toluene (200 mL) was added m- (aminomethyl). 13.6 g (100 mmol, 1.13 eq) of benzylamine was added. After a catalytic amount of p-TsOH.H ₂ O (about 100 mg) was added, the mixture was refluxed in a water separator for 12 hours (about 5 mL of water was removed). Thereafter, additional 5.5 g (40 mmol) of m- (aminomethyl) benzylamine was added and the mixture was boiled for an additional 11 hours. Next, toluene was distilled off (760 Torr). The resulting crude product was distilled under high vacuum (30 to 105 ° C./0.5 Torr). By further distillation through a Vigreux column (boiling point 105 to 108 ° C./25 Torr) 1- [3-chloro-5- (trifluoromethyl) phenyl] -2,2,2-trifluoroethanamine 16.0 g (58 mmol, 65 %) Is obtained as a clear liquid.

  HPLC-MS: log P = 2.94, mass (m / z): 277.93 (M + H).

¹ H NMR (400 MHz, d ₃ -CD ₃ CN): δ = 7.75 (m, 3H), 4.60 (m, 1H), 2.10 (s, 2H, br).

  In the same manner as described in Step 1 for 1- [3-chloro-5- (trifluoromethyl) phenyl] -2,2,2-trifluoroethanamine, the following compound was also obtained:

2,2,2-trifluoro-1- (3,4,5-trichlorophenyl) ethanamine HPLC-MS: log P = 3.17; mass (m / z): 277.9; 279.9 (M + H) ⁺ .

¹ H NMR (400 MHz, d6-DMSO) δ = 7.84 (s, 2H), 4.63 (m, 1H), 2.72 ppm (brs, 2H).

Stage 2
4-Bromo-N-cyclopropyl-2- (trifluoromethyl) benzamide

４−ブロモ−２−（トリフルオロメチル）安息香酸１．５０ｇ（１当量、５．５７ｍｍｏｌ）（安息香酸の臭素化によるＥＰ１４４５２５３ Ｙａｍａｎｏｕｃｈｉ Ｐｈａｒｍａｃｅｕｔｉｃａｌ Ｃｏ．と同様の合成）をジクロロメタン５ｍＬに溶かした。次に、６−クロロヒドロキシベンゾトリアゾール９５４ｍｇ（１．０当量、５．５７ｍｍｏｌ）、Ｎ−（３−ジメチルアミノプロピル）−Ｎ′−エチルカルボジイミド塩酸塩１．２８ｇ（１．２当量、６．６９ｍｍｏｌ）およびＮ−エチルジイソプロピルアミン１．４５ｍＬ（１．５当量、８．６３ｍｍｏｌ）をそれに加え、混合物をＲＴで２０分撹拌した。次に、シクロプロピルアミン４７７ｍｇ（１．５当量、８．３６ｍｍｏｌ）をそれに加え、反応混合物を室温で１２時間撹拌した。その後、混合物を減圧下に濃縮し、粗生成物を酢酸エチル（ＥＡ）に溶かした。溶液を緩衝溶液（０．５Ｍリン酸緩衝液ｐＨ＝７）で２回洗浄し、ＭｇＳＯ_４で脱水した。その精製を、溶離液であるシクロヘキサン／酢酸エチル（ＥＡ）（０％ＥＡから１００％ＥＡ）を用いるシリカゲルクロマトグラフィーによって行った。これによって、白色固体として４−ブロモ−Ｎ−シクロプロピル−２−（トリフルオロメチル）ベンズアミド８３１ｍｇ（４８％）を得る。

4-Bromo-2- (trifluoromethyl) benzoic acid 1.50 g (1 eq, 5.57 mmol) (similar to EP 14445253 Yamano Pharmaceutical Co. by bromination of benzoic acid) was dissolved in 5 mL of dichloromethane. Next, 954 mg (1.0 equivalent, 5.57 mmol) of 6-chlorohydroxybenzotriazole, 1.28 g (1.2 equivalent, 6.69 mmol) of N- (3-dimethylaminopropyl) -N′-ethylcarbodiimide hydrochloride ) And 1.45 mL (1.5 eq, 8.63 mmol) of N-ethyldiisopropylamine were added thereto and the mixture was stirred at RT for 20 min. Next, 477 mg (1.5 eq, 8.36 mmol) of cyclopropylamine was added thereto and the reaction mixture was stirred at room temperature for 12 hours. The mixture was then concentrated under reduced pressure and the crude product was dissolved in ethyl acetate (EA). The solution was washed twice with buffer solution (0.5 M phosphate buffer pH = 7) and dried over MgSO ₄ . The purification was performed by silica gel chromatography using the eluent cyclohexane / ethyl acetate (EA) (0% EA to 100% EA). This gives 831 mg (48%) of 4-bromo-N-cyclopropyl-2- (trifluoromethyl) benzamide as a white solid.

HPLC-MS: log P = 2.13; mass (m / z): 309.91 (M + H) ^<+> .

¹ H NMR (400 MHz, d3-CD3CN): δ = 8.26 (s, 1H, br), 7.90 (s, 1H), 7.88 (d, 1H), 7.43 (d, 1H) 2.80 (m, 1H), 0.70 (m, 2H), 0.50 (m, 2H).

  The following compounds were also obtained in the same manner as described in Synthesis Example 4, Step 1.

4-Bromo-N- (pyridin-2-yl) -2- (trifluoromethyl) benzamide From 4-bromo-2- (trifluoromethyl) benzoic acid.

HPLC-MS: log P = 2.57; mass (m / z): 344.92 (M + H) ^<+> .

¹ H NMR (400 MHz, d ₃ -CD ₃ CN): δ = 8.90 (s, 1H, br), 8.30 (d, 1H), 8.15 (d, 1H), 7.95 (s) 1H), 7.85 (d, 1H), 7.80 (dd, 1H), 7.60 (d, 1H), 7.13 (m, 1H).

Procedure from N-benzyl-4-bromo-2- (trifluoromethyl) benzamide 4-bromo-2- (trifluoromethyl) benzoic acid.

HPLC-MS: log P = 2.89; mass (m / z): 359.85 (M + H) ^<+> .

¹ H NMR (400 MHz, d ₃ -CD ₃ CN): δ = 7.90 (s, 1H), 7.80 (dd, 1H), 7.45 (d, 1H), 7.35 (m, 5H) ), 7.30 (m, 1H), 4.50 (d, 2H).

4-Bromo-N- (pyridin-2-ylmethyl) -2- (trifluoromethyl) benzamide Procedure from 4-bromo-2- (trifluoromethyl) benzoic acid.

HPLC-MS: log P = 1.56; mass (m / z): 360.91 (M + H) ^<+> .

¹ H NMR (400 MHz, d ₃ -CD ₃ CN): δ = 8.50 (d, 1H), 7.90 (s, 1H), 7.85 (d, 1H), 7.73 (dd, 1H) ), 7.50 (d, 1H), 7.35 (d, 1H), 7.30 (s, 1H, br), 7.23 (m, 1H), 4.60 (d, 2H).

Procedure from 4-bromo-2-methyl-N- (pyridin-2-ylmethyl) benzamide 4-bromo-2-methylbenzoic acid.

HPLC-MS: log P = 1.40; mass (m / z): 306.95 (M + H) ^<+> .

¹ H NMR (400 MHz, d ₃ -CD ₃ CN): δ = 8.50 (t, 1H), 7.73 (t, 1H), 7.45 (s, 1H), 7.40 (d, 1H) ), 7.35 (m, 3H), 7.20 (dd, 1H), 4.60 (d, 2H), 2.40 (s, 3H).

Procedure from 4- bromo-N-cyclopropyl -2-methylbenzamide 4-bromo-2-methylbenzoic acid.

¹ H NMR (400 MHz, d ₃ -CD ₃ CN): δ = 7.45 (s, 1H), 7.35 (d, 1H), 7.20 (d, 1H), 6.80 (s, 1H) Br), 2.80 (m, 1H), 2.40 (s, 3H), 0.70 (m, 2H), 0.55 (m, 2H).

Stage 3
(2E) -3- [4- (Cyclopropylcarbamoyl) -3-trifluoromethylphenyl] acrylic acid

３０ｍＬマイクロ波容器中、４−ブロモ−Ｎ−シクロプロピル−２−（トリフルオロメチル）ベンズアミド１．１８ｇ（１当量、３．８４ｍｍｏｌ）および（２Ｅ）−３−（４，４，５，５−テトラメチル−１，３，２−ジオキサボロラン−２−イル）アクリル酸エチル８６８ｍｇ（１当量、３．８４ｍｍｏｌ）を１，４−ジオキサン８ｍＬに溶かした。これに、Ｎａ_２ＣＯ_３９ｍＬ（２Ｍ水溶液）およびビス（トリシクロヘキシルホスフィン）−二塩化パラジウム（ＩＩ）２８３ｍｇ（０．１当量、０．３８ｍｍｏｌ）を加え、反応混合物をアルゴンで５分間飽和させた。次に、反応混合物をマイクロ波装置（ＣＥＭ Ｄｉｓｃｏｖｅｒ）において１５０℃（８０ワット）で１０分間加熱した。次に、ジオキサン溶液を傾斜法で除去し、残留物を１，４−ジオキサンで洗浄し、合わせた有機相を減圧下に濃縮した。残留物を水に溶かし、少量のジエチルエーテルで洗浄した。次に、混合物を１Ｍ ＨＣｌでｐＨ＝３の酸性とし、得られた水溶液を酢酸エチル（ＥＡ）で抽出した。有機相の脱水および濃縮後に、（２Ｅ，Ｚ）−３−［４−（シクロプロピルカルバモイル）−３−（トリフルオロメチル）フェニル］アクリル酸４１２ｍｇ（３５％）を白色固体として得た。

In a 30 mL microwave vessel 1.18 g (1 eq, 3.84 mmol) 4-bromo-N-cyclopropyl-2- (trifluoromethyl) benzamide and (2E) -3- (4,4,5,5- 868 mg (1 equivalent, 3.84 mmol) of ethyl tetramethyl-1,3,2-dioxaborolan-2-yl) acrylate was dissolved in 8 mL of 1,4-dioxane. To this was added 9 mL Na ₂ CO ₃ (2M aqueous solution) and 283 mg (0.1 eq, 0.38 mmol) bis (tricyclohexylphosphine) -palladium (II) dichloride and the reaction mixture was saturated with argon for 5 min. . The reaction mixture was then heated at 150 ° C. (80 watts) for 10 minutes in a microwave apparatus (CEM Discover). The dioxane solution was then removed by decantation, the residue was washed with 1,4-dioxane, and the combined organic phases were concentrated under reduced pressure. The residue was dissolved in water and washed with a small amount of diethyl ether. The mixture was then acidified with 1M HCl to pH = 3 and the resulting aqueous solution was extracted with ethyl acetate (EA). After dehydration and concentration of the organic phase, 412 mg (35%) of (2E, Z) -3- [4- (cyclopropylcarbamoyl) -3- (trifluoromethyl) phenyl] acrylic acid was obtained as a white solid.

HPLC-MS: log P = 1.34, mass (m / z): 300.03 (M + H) ^<+> .

¹ H NMR (400 MHz, d ₃ -CD ₃ CN): δ = 7.90 (s, 1H), 7.80 (d, 1H), 7.70 (d, 1H, J = 16 Hz), 7.50 (D, 1H), 6.60 (s, 1H, br), 6.55 (d, 1H, J = 16 Hz), 2.80 (m, 1H), 0.75 (m, 2H),. 55 (m, 2H).

  In the same manner as in the method described in Synthesis Example 4 Step 2, the following compound of the general formula II-1 was also obtained.

(2E) -3- [4- (Pyridin-2-yl) carbamoyl) -3-trifluoromethylphenyl] acrylic acid 4-bromo-N- (pyridin-2-yl) -2- (trifluoromethyl) benzamide Procedure from.

HPLC-MS: log P = 1.69; mass (m / z): 337.04 (M + H) ^<+> .

¹ H NMR (400 MHz, d ₃ -CD ₃ CN): δ = 8.30 (d, 1H, br), 8.15 (m, 2H), 8.00 (s, 1H), 7.90 (d 1H), 7.80 (m, 1H), 7.60 (m, 2H), 7.10 (m, 1H), 6.60 (d, 1H, J = 16 Hz).

Procedure from (2E) -3- [4- (phenylmethyl) carbamoyl) -3-trifluoromethylphenyl] acrylic acid N-benzyl-4-bromo-2- (trifluoromethyl) benzamide.

HPLC-MS: log P = 2.12, mass (m / z): 350.1 (M + H) ^<+> .

¹ H NMR (400 MHz, d ₃ -CD ₃ CN): δ = 7.98 (s, 1H), 7.88 (d, 1H), 7.70 (d, 1H, J = 16 Hz), 7.55 (D, 1H), 7.35 (m, 5H), 7.29 (m, 1H, br), 6.60 (d, 1H, J = 16 Hz), 4.51 (d, 2H).

(2E) -3- [4- (Pyridin-2-ylmethyl) carbamoyl) -3-trifluoromethylphenyl] acrylic acid 4-bromo-N- (pyridin-2-ylmethyl) -2- (trifluoromethyl) benzamide Procedure from.

HPLC-MS: log P = 0.91; mass (m / z): 350.9 (M + H) ^<+> .

(2E) -3- [4- (Cyclopropylcarbamoyl) -3-methylphenyl] acrylic acid Procedure from 4-bromo-N-cyclopropyl-2- (methyl) benzamide.

HPLC-MS: log P = 1.14; mass (m / z): 246.09 (M + H) ^<+> .

¹ H NMR (400 MHz, d ³ -CD ₃ CN): δ = 7.60 (d, 1H, J = 16 Hz), 7.45 (m, 2H), 7.30 (d, 1H), 7.20 (D, 1H), 6.45 (d, 1H, J = 16 Hz), 2.90 (m, 1H), 2.35 (s, 3H), 0.75 (m, 2H), 0.55 ( m, 2H).

Stage 4
4-[(1E, Z) -3-({1- [3-Chloro-5- (trifluoromethyl) phenyl] -2,2,2-trifluoroethyl} amino) -3-oxoprop-1-ene -1-yl] -N-cyclopropyl-2- (trifluoromethyl) benzamide (Compound No. Ia-40 in Table 1)

（２Ｅ，Ｚ）−３−［４−（シクロプロピルカルバモイル）−３−（トリフルオロメチル）フェニル］−アクリル酸１００ｍｇ（１当量、０．２９ｍｍｏｌ）をジクロロメタン１ｍＬに溶かした。次に、６−クロロヒドロキシベンゾトリアゾール５０ｍｇ（１．０当量、０．２９ｍｍｏｌ）、Ｎ−（３−ジメチルアミノプロピル）−Ｎ′−エチル−カルボジイミド塩酸塩７３ｍｇ（１．３当量、０．３８ｍｍｏｌ）およびＮ−エチルジイソプロピルアミン１０２μＬ（２当量、０．５８ｍｍｏｌ）をそれに加え、混合物をＲＴで２０分撹拌した。次に、１−［３−クロロ−５−（トリフルオロメチル）フェニル］−２，２，２−トリフルオロエタンアミン９８ｍｇ（１．３当量、０．３５ｍｍｏｌ）をそれに加え、反応混合物を室温で１２時間撹拌した。その後、混合物を減圧下に濃縮し、粗生成物を酢酸エチル（ＥＡ）に溶かした。溶液を緩衝溶液（０．５Ｍリン酸緩衝液ｐＨ＝７）で２回洗浄し、ＭｇＳＯ_４で脱水した。精製を溶離液シクロヘキサン／酢酸エチル（ＥＡ）（０％ＥＡから１００％ＥＡ）を用いるシリカゲルクロマトグラフィーによって行った。これによって、４−［（１Ｅ，Ｚ）−３−（｛１−［３−クロロ−５−（トリフルオロメチル）フェニル］−２，２，２−トリフルオロエチル｝アミノ）−３−オキソプロプ−１−エン−１−イル］−Ｎ−シクロプロピル−２−（トリフルオロメチル）ベンズアミド６１ｍｇ（３７％）が固体として得られる。

100 mg (1 equivalent, 0.29 mmol) of (2E, Z) -3- [4- (cyclopropylcarbamoyl) -3- (trifluoromethyl) phenyl] -acrylic acid was dissolved in 1 mL of dichloromethane. Next, 6-chlorohydroxybenzotriazole 50 mg (1.0 equivalent, 0.29 mmol), N- (3-dimethylaminopropyl) -N'-ethyl-carbodiimide hydrochloride 73 mg (1.3 equivalent, 0.38 mmol) And 102 μL (2 eq, 0.58 mmol) of N-ethyldiisopropylamine were added thereto and the mixture was stirred at RT for 20 min. Next, 98 mg (1.3 eq, 0.35 mmol) of 1- [3-chloro-5- (trifluoromethyl) phenyl] -2,2,2-trifluoroethanamine was added thereto and the reaction mixture was allowed to come to room temperature. Stir for 12 hours. The mixture was then concentrated under reduced pressure and the crude product was dissolved in ethyl acetate (EA). The solution was washed twice with buffer solution (0.5 M phosphate buffer pH = 7) and dried over MgSO ₄ . Purification was performed by silica gel chromatography using the eluent cyclohexane / ethyl acetate (EA) (0% EA to 100% EA). Thereby, 4-[(1E, Z) -3-({1- [3-chloro-5- (trifluoromethyl) phenyl] -2,2,2-trifluoroethyl} amino) -3-oxoprop- 61 mg (37%) of 1-en-1-yl] -N-cyclopropyl-2- (trifluoromethyl) benzamide are obtained as a solid.

HPLC-MS: log P = 3.68, mass (m / z): 558.97 (M + H) ^<+> .

¹ H NMR (400 MHz, d ₆ -DMSO): δ = 9.51 (d, 1H), 8.55 (d, 1H), 8.12 (s, 1H), 8.08 (s, 1H), 8.03-7.95 (m, 2H), 7.93 (d, 1H), 7.66 (d, 1H, J = 16 Hz), 7.54 (d, 1H), 6.93 (d, 1H, J = 16 Hz), 6.26 (m, 1H), 2.79 (m, 1H), 0.70 (m, 2H), 0.50 (m, 2H).

Synthesis Example 5 (Production of compounds of general formulas I-1 and II-2 according to schemes 1 and 8)
Stage 1
(2E) -3- [3-Cyano-4- (1H-1,2,4-triazol-1-yl) phenyl] acrylic acid

５−ホルミル−２−（１Ｈ−１，２，４−トリアゾール−１−イル）ベンゾニトリル（文献：ＷＯ−Ａ−２００８／０１９７６０）２．０５ｇ（１０．３ｍｍｏｌ）、マロン酸１．６０ｇ（１６．６ｍｍｏｌ）およびピペリジン１７６ｍｇ（２．０７ｍｍｏｌ）をピリジン２０ｍＬ中にて８０℃で４８時間撹拌した。ピリジンを減圧下に留去した。残留物を氷水に加え、濃塩酸でｐＨ１に調節した。水相を酢酸エチルで繰り返し抽出し、硫酸ナトリウムで脱水し、溶媒を減圧下に留去した。

5-formyl-2- (1H-1,2,4-triazol-1-yl) benzonitrile (literature: WO-A-2008 / 019760) 2.05 g (10.3 mmol), malonic acid 1.60 g (16 .6 mmol) and 176 mg (2.07 mmol) of piperidine were stirred in 20 mL of pyridine at 80 ° C. for 48 hours. Pyridine was distilled off under reduced pressure. The residue was added to ice water and adjusted to pH 1 with concentrated hydrochloric acid. The aqueous phase was extracted repeatedly with ethyl acetate, dehydrated with sodium sulfate, and the solvent was distilled off under reduced pressure.

  Yield: 2.00 g (77% of theory).

HPLC-MS: log P = 0.97; mass (m / z): 241.1 (M + H) ^<+> .

Stage 2
(2E) -3- [3-Cyano-4- (1H-1,2,4-triazol-1-yl) phenyl] acrylic acid (Compound No. Ia-17 in Table 1)

実施例５段階１からの２（２Ｅ）−３−［３−シアノ−４−（１Ｈ−１，２，４−トリアゾール−１−イル）フェニル］アクリル酸１００ｍｇ（０．４１ｍｍｏｌ）およびＥＤＣ９６．０ｍｇ（０．５０ｍｍｏｌ）を最初に、ジオキサン２ｍＬに入れ、３０分間撹拌した。次に、２，２，２−トリフルオロ−１−［３，４−ジクロロフェニル］エタンアミン（ＣＡＳ登録番号８８６３６９−７４−０）１０１ｍｇ（０．４１ｍｍｏｌ）を加え、混合物を室温でさらに１８時間撹拌した。ジオキサンをロータリーエバポレータで留去し、残留物を水に取り、酢酸エチルで繰り返し抽出した。有機相を硫酸ナトリウムで脱水し、溶媒をロータリーエバポレータで留去した。残留物について、溶離液としてシクロヘキサン／酢酸エチルを用いるシリカゲルでのクロマトグラフィー（勾配＝２時間かけて０％酢酸エチルから１００％酢酸エチル）を行った。

Example 5 100 mg (0.41 mmol) of 2 (2E) -3- [3-cyano-4- (1H-1,2,4-triazol-1-yl) phenyl] acrylic acid from Step 1 and 96.0 mg of EDC (0.50 mmol) was first placed in 2 mL of dioxane and stirred for 30 minutes. Next, 101 mg (0.41 mmol) of 2,2,2-trifluoro-1- [3,4-dichlorophenyl] ethanamine (CAS Registry Number 886369-74-0) was added and the mixture was stirred at room temperature for a further 18 hours. . Dioxane was distilled off on a rotary evaporator, the residue was taken up in water and extracted repeatedly with ethyl acetate. The organic phase was dehydrated with sodium sulfate and the solvent was distilled off on a rotary evaporator. The residue was chromatographed on silica gel using cyclohexane / ethyl acetate as eluent (gradient = 0% ethyl acetate to 100% ethyl acetate over 2 hours).

  Yield: 69.0 mg (62% of theory).

¹ H NMR (d ₆ -DMSO) δ = 6.05 (m, 1H), 6.95 (d, 1H), 7.62 (m, 2H), 7.71 (m, 1H), 7.94 (M, 1H), 8.08 (m, 1H), 8.29 (m, 1H), 8.35 (m, 1H), 9.18 (s, 1H), 9.35 (d, 1H) .

HPLC-MS: log P = 3.22; mass (m / z): 466.0 (M + H) ^<+> .

Synthesis Example 6 (Production of compounds of general formulas I-1 and I-9 according to Schemes 1 and 5)
Stage 1
5-Cyano-N- {2,2,2-trifluoro-1- [3- (trifluoromethyl) phenyl] ethyl} -1-benzofuran-2-carboxamide (Compound No. Ic-1 in Table 3)

２，２，２−トリフルオロ−１−［３−トリフルオロメチルフェニル］エタンアミン（４００ｍｇ、１．６４ｍｍｏｌ）のＮ，Ｎ−ジメチルホルムアミド（５ｍＬ）中溶液を、５−シアノベンゾフラン−２−カルボン酸（４００ｍｇ、２．１３ｍｍｏｌ）、ＨＢＴＵ（８１１ｍｇ、２．１３ｍｍｏｌ）およびＮ−メチルモルホリン（５４９ｍｇ、２．１３ｍｍｏｌ）と混合し、室温で終夜撹拌した。次に、反応混合物を減圧下に濃縮し、酢酸エチルに取り、炭酸水素ナトリウム溶液（１０％）および飽和塩化ナトリウム溶液の順で洗浄した。有機相を硫酸ナトリウムで脱水し、濾過し、減圧下に濃縮した。残留物について、溶離液としてシクロヘキサン／酢酸エチルを用いるシリカゲルでのクロマトグラフィーを行った（勾配＝２時間かけて０％酢酸エチルから２０％酢酸エチル）。

A solution of 2,2,2-trifluoro-1- [3-trifluoromethylphenyl] ethanamine (400 mg, 1.64 mmol) in N, N-dimethylformamide (5 mL) was added to 5-cyanobenzofuran-2-carboxylic acid. (400 mg, 2.13 mmol), HBTU (811 mg, 2.13 mmol) and N-methylmorpholine (549 mg, 2.13 mmol) were mixed and stirred at room temperature overnight. The reaction mixture was then concentrated under reduced pressure, taken up in ethyl acetate and washed successively with sodium bicarbonate solution (10%) and saturated sodium chloride solution. The organic phase was dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was chromatographed on silica gel using cyclohexane / ethyl acetate as eluent (gradient = 0% ethyl acetate to 20% ethyl acetate over 2 hours).

  Yield: 467.6 mg (68% of theory).

HPLC-MS: log P = 3.63; mass (m / z): 413.0 (M + H) ⁺ ; ¹ H NMR (CD ₃ CN) 6.06-6.12 (m, 1H), 7.60 ( s, 1H), 7.64-7.68 (m, 1H), 7.73-7.80 (m, 4H), 7.85-7.87 (m, 1H), 7.95 (m, 1H), 8.16 (m, 1H).

Stage 2
5- (Aminomethyl) -N- {2,2,2-trifluoro-1- [3- (trifluoromethyl) phenyl] ethyl} -1-benzofuran-2-carboxamide

５−シアノ−Ｎ−｛２，２，２−トリフルオロ−１−［３−（トリフルオロメチル）フェニル］エチル｝−１−ベンゾフラン−２−カルボキサミド（２７３ｍｇ、０．６６ｍｍｏｌ）のメタノール（１０ｍＬ）中溶液を濃塩酸（０．４２ｍＬ）およびパラジウム／炭素（１０％；５０ｍｇ）と混合し、水素雰囲気下に２時間撹拌した。反応混合物をセライト（登録商標）およびシリカゲル層で濾過した。

5-cyano-N- {2,2,2-trifluoro-1- [3- (trifluoromethyl) phenyl] ethyl} -1-benzofuran-2-carboxamide (273 mg, 0.66 mmol) in methanol (10 mL) The medium solution was mixed with concentrated hydrochloric acid (0.42 mL) and palladium / carbon (10%; 50 mg) and stirred for 2 hours under a hydrogen atmosphere. The reaction mixture was filtered through Celite® and silica gel layers.

  Yield: 297.4 mg (107% of theory).

HPLC-MS: log P = 2.02; mass (m / z): 415.1 (M−H) ⁻ ; ¹ H NMR (CD ₃ CN) 3.90 (s, 1H), 6.09 (m, 1H), 7.42-7.68 (m, 6H), 7.74-8.07 (m, 5H).

Stage 3
5- (acetamidomethyl) -N- {2,2,2-trifluoro-1- [3- (trifluoromethyl) phenyl] ethyl} -1-benzofuran-2-carboxamide (Compound Ic-10 in Table 3) )

５−（アミノメチル）−Ｎ−｛２，２，２−トリフルオロ−１−［３−（トリフルオロメチル）フェニル］エチル｝−１−ベンゾフラン−２−カルボキサミド（５０ｍｇ、０．１２ｍｍｏｌ）のジクロロメタン（１ｍＬ）中溶液を、ピリジン（０．０１ｍＬ）と混合し、冷却して０℃とした。次に、アセチルクロライド（９μＬ、０．１２ｍｍｏｌ）を滴下し、混合物を終夜にて昇温させて室温とした。混合物を酢酸エチルで希釈し、塩酸（１Ｍ）で洗浄した。有機相を硫酸ナトリウムで脱水し、濾過し、減圧下に濃縮した。残留物について、溶離液として水／アセトニトリルを用いる分取ＨＰＬＣでのクロマトグラフィーを行った（勾配＝４３分かけて１０％アセトニトリル／水から１００％アセトニトリル）。

5- (Aminomethyl) -N- {2,2,2-trifluoro-1- [3- (trifluoromethyl) phenyl] ethyl} -1-benzofuran-2-carboxamide (50 mg, 0.12 mmol) in dichloromethane The solution in (1 mL) was mixed with pyridine (0.01 mL) and cooled to 0 ° C. Next, acetyl chloride (9 μL, 0.12 mmol) was added dropwise and the mixture was allowed to warm to room temperature overnight. The mixture was diluted with ethyl acetate and washed with hydrochloric acid (1M). The organic phase was dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was chromatographed on preparative HPLC using water / acetonitrile as eluent (gradient = 10% acetonitrile / water to 100% acetonitrile over 43 minutes).

  Yield: 10.8 mg (19% of theory).

HPLC-MS: log P = 2.80; mass (m / z): 459.1 (M + H) ⁺ ; ¹ H NMR (CD ₃ CN) 2.15 (s, 3H), 4.41 (d, 2H) 6.13 (5-fold line, 1H), 6.88 (brs, 1H), 7.40-7.42 (m, 1H), 7.51-7.56 (m, 2H), 7.62. -7.69 (m, 2H), 7.76-7.78 (m, 1H), 7.88-7.90 (m, 1H), 7.97-7.99 (m, 1H), 8 .21-8.23 (m, 1H).

Synthesis Example 7 (Production of compounds of general formulas I-6 and II-3 according to schemes 1, 4 and 9)
Stage 1
Tert-Butyl 4-formyl-3-hydroxybenzoate

４−ホルミル−３−ヒドロキシ安息香酸の溶液（１ｇ、６．０ｍｍｏｌ）をテトラヒドロフラン（１０ｍＬ）に溶かし、加熱還流した。次に、Ｎ，Ｎ−ジメチルホルムアミドジ−ｔｅｒｔ−ブチルアセタールを滴下し（５．７７ｍＬ、２４．０ｍｍｏｌ）、混合物をその温度で１．５時間撹拌した。冷却した溶液を減圧下に濃縮し、残留物を溶離液としてシクロヘキサン／酢酸エチルを用いるシリカゲルでクロマトグラフィー精製した（勾配＝１時間かけて０％酢酸エチルから５％酢酸エチル）。

A solution of 4-formyl-3-hydroxybenzoic acid (1 g, 6.0 mmol) was dissolved in tetrahydrofuran (10 mL) and heated to reflux. N, N-dimethylformamide di-tert-butyl acetal was then added dropwise (5.77 mL, 24.0 mmol) and the mixture was stirred at that temperature for 1.5 hours. The cooled solution was concentrated under reduced pressure and the residue was chromatographed on silica gel using cyclohexane / ethyl acetate as eluent (gradient = 0% ethyl acetate to 5% ethyl acetate over 1 hour).

  Yield: 1.13 g (84% of theory).

HPLC-MS: log P = 3.11; mass (m / z): 223.1 (M + H) ⁺ ; ¹ H NMR (CD ₃ CN) 1.58 (s, 9H), 7.48 (s, 1H) 7.57 (d, 1H), 7.76 (d, 1H).

Stage 2
1-benzofuran-2,6-dicarboxylic acid 6-tert-butyl 2-ethyl

４−ホルミル−３−ヒドロキシ安息香酸ｔｅｒｔ−ブチル（１．２ｇ、５，４０ｍｍｏｌ）および炭酸カリウム（１７２６ｍｇ、１２．４ｍｍｏｌ）のＤＭＦ（１７ｍＬ）中溶液にブロモ酢酸エチル（０．５６ｍＬ、５．０ｍｍｏｌ）を滴下混合し、８０℃で６時間撹拌した。次に、ブロモ酢酸エチル（０．２８ｍＬ、２．５ｍｍｏｌ）を再度加え、混合物を８０℃で終夜撹拌した。冷却して室温とした後、反応混合物を氷水に加え、酢酸エチルで抽出した。有機相を硫酸ナトリウムで脱水し、濾過し、減圧下に濃縮して乾固させた。

Ethyl bromoacetate (0.56 mL, 5.0 mmol) in a solution of tert-butyl 4-formyl-3-hydroxybenzoate (1.2 g, 5,40 mmol) and potassium carbonate (1726 mg, 12.4 mmol) in DMF (17 mL). ) Was added dropwise and stirred at 80 ° C. for 6 hours. Then ethyl bromoacetate (0.28 mL, 2.5 mmol) was added again and the mixture was stirred at 80 ° C. overnight. After cooling to room temperature, the reaction mixture was added to ice water and extracted with ethyl acetate. The organic phase was dried over sodium sulfate, filtered and concentrated to dryness under reduced pressure.

  Yield 497.3 mg (32% of theory).

HPLC-MS: log P = 4.32; mass (m / z): 235.1 (M-C ₄ H ₉ + 2H) ⁺ ; ¹ H NMR (CD ₃ CN) 1.38 (t, 3H), 60 (s, 9H), 4.40 (q, 2H), 7.59 (s, 1H), 7.79 (d, 1H), 7.93 (d, 1H), 8.19 (s, 1H) ).

Stage 3
6- (tert-Butoxycarbonyl) -1-benzofuran-2-carboxylic acid

１−ベンゾフラン−２，６−ジカルボン酸６−ｔｅｒｔ−ブチル２−エチル（４９０ｍｇ、１．６８ｍｍｏｌ）のエタノール（１５ｍＬ）中溶液を水酸化ナトリウム溶液（３．３６ｍＬ、１Ｍ）と混合し、２時間加熱還流した。冷却した溶液を氷冷した塩酸（１Ｍ）に加え、沈殿を吸引によって濾過し、少量の水で洗浄し、真空乾燥した。

A solution of 6-tert-butyl 2-ethyl 1-benzofuran-2,6-dicarboxylate (490 mg, 1.68 mmol) in ethanol (15 mL) was mixed with sodium hydroxide solution (3.36 mL, 1 M) for 2 hours. Heated to reflux. The cooled solution was added to ice-cold hydrochloric acid (1M) and the precipitate was filtered off with suction, washed with a small amount of water and dried in vacuo.

  Yield: 353 mg (80% of theory).

HPLC-MS: log P = 2.58; mass (m / z): 261.1 (M + H) ⁺ ; ¹ H NMR (CD ₃ CN) 1.60 (s, 9H), 7.60 (s, 1H) 7.79 (d, 1H), 7.92-7.94 (m, 1H), 8.19 (s, 1H).

Stage 4
2-({2,2,2-trifluoro-1- [3- (trifluoromethyl) phenyl] ethyl} carbamoyl) -1-benzofuran-6-carboxylic acid tert-butyl

６−（ｔｅｒｔ−ブトキシカルボニル）−１−ベンゾフラン−２−カルボン酸（３５０ｍｇ、１．３３ｍｍｏｌ）および２，２，２−トリフルオロ−１−［３−トリフルオロメチルフェニル］エタンアミン（３５７ｍｇ、１．４６ｍｍｏｌ）のＮ，Ｎ−ジメチルホルムアミド（５ｍＬ）中溶液を４−（４，６−ジメトキシ［１．３．５］トリアジン−２−イル）−４−メチルモルホリニウムクロライド水和物（３０４ｍｇ、１．４６ｍｍｏｌ）と混合し、密閉容器中にて５０℃で終夜撹拌した。冷却した反応溶液を塩酸（１Ｍ）と混合し、酢酸エチルで抽出した。有機相を飽和炭酸水素ナトリウム溶液および飽和塩化ナトリウム溶液で洗浄し、硫酸ナトリウムで脱水し、濾過し、減圧下に濃縮して乾固させた。これによって、ｔｅｒｔ−ブチルエステルおよび遊離酸の混合物として４５３ｍｇが残り、それをそれ以上精製せずに次の段階で用いた。

6- (tert-Butoxycarbonyl) -1-benzofuran-2-carboxylic acid (350 mg, 1.33 mmol) and 2,2,2-trifluoro-1- [3-trifluoromethylphenyl] ethanamine (357 mg, 1. 46 mmol) in N, N-dimethylformamide (5 mL) was added 4- (4,6-dimethoxy [1.3.5] triazin-2-yl) -4-methylmorpholinium chloride hydrate (304 mg, 1.46 mmol) and stirred in a sealed container at 50 ° C. overnight. The cooled reaction solution was mixed with hydrochloric acid (1M) and extracted with ethyl acetate. The organic phase was washed with saturated sodium bicarbonate solution and saturated sodium chloride solution, dried over sodium sulfate, filtered and concentrated to dryness under reduced pressure. This left 453 mg as a mixture of tert-butyl ester and free acid, which was used in the next step without further purification.

Stage 5
2-({2,2,2-trifluoro-1- [3- (trifluoromethyl) phenyl] ethyl} carbamoyl) -1-benzofuran-6-carboxylic acid

２−（｛２，２，２−トリフルオロ−１−［３−（トリフルオロメチル）フェニル］エチル｝カルバモイル）−１−ベンゾフラン−６−カルボン酸ｔｅｒｔ−ブチル（４５０ｍｇ、１．０４ｍｍｏｌ）のジクロロメタン（４．５ｍＬ）中溶液を０℃でトリフルオロ酢酸（０．４６ｍＬ、６．０ｍｍｏｌ）と混合し、室温で終夜撹拌した。次に、反応混合物を水で洗浄し、有機相を硫酸マグネシウムで脱水し、濾過し、減圧下に濃縮した。残留物をシリカゲルで濾過し、フィルターケーキを酢酸エチルおよびメタノールで洗い、濾液を濃縮した。

2-({2,2,2-trifluoro-1- [3- (trifluoromethyl) phenyl] ethyl} carbamoyl) -1-benzofuran-6-carboxylate tert-butyl (450 mg, 1.04 mmol) in dichloromethane The solution in (4.5 mL) was mixed with trifluoroacetic acid (0.46 mL, 6.0 mmol) at 0 ° C. and stirred at room temperature overnight. The reaction mixture was then washed with water and the organic phase was dried over magnesium sulfate, filtered and concentrated under reduced pressure. The residue was filtered through silica gel, the filter cake was washed with ethyl acetate and methanol, and the filtrate was concentrated.

  Yield: 266 mg (59% of theory).

HPLC-MS: log P = 3.10; mass (m / z): 430.1 (M−H) ⁻ ; ¹ H NMR (CD ₃ CN) 6.05-6.10 (m, 1H), 7. 52-8.19 (m, 9H).

Stage 6
N ⁶ -Cyclopropyl-N ² -{2,2,2-trifluoro-1- [3- (trifluoromethyl) phenyl] ethyl} -1-benzofuran-2,6-dicarboxamide (Compound Ic-19 in Table 3)

２−（｛２，２，２−トリフルオロ−１−［３−（トリフルオロメチル）フェニル］エチル｝カルバモイル）−１−ベンゾフラン−６−カルボン酸（１００ｍｇ、０．２１ｍｍｏｌ）のＮ，Ｎ−ジメチルホルムアミド（１ｍＬ）中溶液を４−（４，６−ジメトキシ［１．３．５］トリアジン−２−イル）−４−メチルモルホリニウムクロライド水和物（１００ｍｇ、０．４６ｍｍｏｌ）およびシクロプロピルアミン（３６ｍｇ、０．６３ｍｍｏｌ）と混合し、密閉容器中にて５０℃で終夜撹拌した。冷却した反応溶液を塩酸（１Ｍ）と混合し、酢酸エチルで抽出した。有機相を飽和炭酸水素ナトリウム溶液および飽和塩化ナトリウム溶液で洗浄し、硫酸ナトリウムで脱水し、濾過し、減圧下に濃縮して乾固させた。残留物について、溶離液として水／アセトニトリルを用いる分取ＨＰＬＣでのクロマトグラフィーを行った（勾配＝４３分かけて１０％アセトニトリル／水から１００％アセトニトリル）。

2-({2,2,2-trifluoro-1- [3- (trifluoromethyl) phenyl] ethyl} carbamoyl) -1-benzofuran-6-carboxylic acid (100 mg, 0.21 mmol) N, N- A solution in dimethylformamide (1 mL) was added 4- (4,6-dimethoxy [1.3.5] triazin-2-yl) -4-methylmorpholinium chloride hydrate (100 mg, 0.46 mmol) and cyclopropyl. Mix with amine (36 mg, 0.63 mmol) and stir in a sealed container at 50 ° C. overnight. The cooled reaction solution was mixed with hydrochloric acid (1M) and extracted with ethyl acetate. The organic phase was washed with saturated sodium bicarbonate solution and saturated sodium chloride solution, dried over sodium sulfate, filtered and concentrated to dryness under reduced pressure. The residue was chromatographed on preparative HPLC using water / acetonitrile as eluent (gradient = 10% acetonitrile / water to 100% acetonitrile over 43 minutes).

  Yield: 18.2 mg (18% of theory).

HPLC-MS: log P = 3.25; mass (m / z): 471.1 (M + H) ⁺ ; ¹ H NMR (CD ₃ CN) 0.61-0.65 (m, 2H), 0.75- 0.79 (m, 2H), 2.85-2.91 (m, 1H), 6.14 (5-wire, 1H), 7.18 (brs, 1H), 7.58 (s, 1H) 7.69-7.79 (m, 4H), 7.89-7.91 (m, 1H), 7.97-7.99 (m, 2H), 8.28 (d, 1H).

Synthesis Example 8 (Production of compounds of general formulas I-6 and II-4 according to schemes 1, 4 and 10)
Stage 1
4-Amino-2-chloro-5-iodobenzoic acid ethyl ester

ヨウ素のエタノール中溶液を硫酸銀（Ｉ）および４−アミノ−２−クロロ安息香酸エチルと混合し、室温で４５分間撹拌した。反応混合物をフリットで濾過し、濾液を減圧下に濃縮した。残留物をＥｔＯＡｃ中でスラリーとし、希炭酸水素ナトリウム溶液と混合した。全てが溶液状態となった時点で、水相を除去し、チオ硫酸ナトリウムをそれに溶かした。有機相を水相で再度洗浄し、その水相を酢酸エチルで抽出した。合わせた有機相を硫酸ナトリウムで脱水し、濾過し、減圧下に濃縮した。溶離液としてシクロヘキサン／酢酸エチルを用いるシリカゲルでのカラムクロマトグラフィー精製を行った（勾配：１０％酢酸エチルから３３％酢酸エチル）。

A solution of iodine in ethanol was mixed with silver (I) sulfate and ethyl 4-amino-2-chlorobenzoate and stirred at room temperature for 45 minutes. The reaction mixture was filtered through a frit and the filtrate was concentrated under reduced pressure. The residue was slurried in EtOAc and mixed with dilute sodium bicarbonate solution. When everything was in solution, the aqueous phase was removed and sodium thiosulfate was dissolved in it. The organic phase was washed again with the aqueous phase and the aqueous phase was extracted with ethyl acetate. The combined organic phases were dried over sodium sulfate, filtered and concentrated under reduced pressure. Column chromatographic purification on silica gel using cyclohexane / ethyl acetate as eluent was performed (gradient: 10% ethyl acetate to 33% ethyl acetate).

  Yield: 1.85 g (74% of theory).

HPLC-MS: log P = 2.95; mass (m / z): 326.0 (M + H) ⁺ ; ¹ H NMR (CD ₃ CN) 1.32 (t, 3H), 4.27 (q, 2H) , 5.01 (brs, 2H), 6.80 (s, 1H), 8.16 (s, 1H).

Stage 2
6-Chloro-5- (ethoxycarbonyl) -1H-indole-2-carboxylic acid

４−アミノ−２−クロロ−５−ヨード安息香酸エチル（１．８２ｇ、５．５９ｍｍｏｌ）のＮ，Ｎ−ジメチルホルムアミド（１８ｍＬ）中溶液をアルゴン下に、ピルビン酸（１．２７ｍＬ、１８．２ｍｍｏｌ）および１，４−ジアザビシクロ［２．２．２］オクタンと混合し、排気し、アルゴンを吹き込んだ。次に、アルゴンを溶液に５分間通し、酢酸パラジウム（ＩＩ）（６８ｍｇ、０．３０ｍｍｏｌ）を加え、混合物を加熱して１００℃として２時間経過させた。冷却した溶液をセライトで濾過し、フィルターケーキを酢酸エチル（１００ｍＬ）で洗った。濾液（懸濁液）を塩酸（２Ｍ；２５ｍＬで２回）および水（２５ｍＬで２回）で洗浄し、硫酸ナトリウムで脱水し、濾過した。濾液を減圧下に濃縮して乾固させ、赤褐色固体（１．９３ｇ、約５１％の生成物）を得て、それをそれ以上精製せずに次の段階に用いた。

A solution of ethyl 4-amino-2-chloro-5-iodobenzoate (1.82 g, 5.59 mmol) in N, N-dimethylformamide (18 mL) under argon, pyruvic acid (1.27 mL, 18.2 mmol). ) And 1,4-diazabicyclo [2.2.2] octane, evacuated and blown with argon. Argon was then passed through the solution for 5 minutes, palladium (II) acetate (68 mg, 0.30 mmol) was added and the mixture was heated to 100 ° C. for 2 hours. The cooled solution was filtered through celite and the filter cake was washed with ethyl acetate (100 mL). The filtrate (suspension) was washed with hydrochloric acid (2M; 2 × 25 mL) and water (2 × 25 mL), dried over sodium sulfate and filtered. The filtrate was concentrated to dryness under reduced pressure to give a reddish brown solid (1.93 g, ˜51% product) that was used in the next step without further purification.

Stage 3
6-chloro-2-({2,2,2-trifluoro-1- [3- (trifluoromethyl) phenyl] ethyl} carbamoyl) -1H-indole-5-carboxylate

粗６−クロロ−５−（エトキシカルボニル）−１Ｈ−インドール−２−カルボン酸生成物（１．９ｇ）および２，２，２−トリフルオロ−１−［３−トリフルオロメチルフェニル］エタンアミン（１．１２ｇ、４．６０ｍｍｏｌ）のＮ，Ｎ−ジメチルホルムアミド（１５ｍＬ）中溶液を４−（４，６−ジメトキシ［１．３．５］トリアジン−２−イル）−４−メチルモルホリニウムクロライド水和物（９５３ｍｇ、４．６０ｍｍｏｌ）と混合し、室温で４日間撹拌した。反応溶液を塩酸（１Ｍ）と混合し、酢酸エチルで抽出した。有機相を飽和炭酸水素ナトリウム溶液および飽和塩化ナトリウム溶液で洗浄し、硫酸ナトリウムで脱水し、濾過し、減圧下に濃縮して乾固させた。溶離液としてシクロヘキサン／酢酸エチルを用いるシリカゲルでのカラムクロマトグラフィー精製を行った（勾配：１０％酢酸エチルから２５％酢酸エチル）。

Crude 6-chloro-5- (ethoxycarbonyl) -1H-indole-2-carboxylic acid product (1.9 g) and 2,2,2-trifluoro-1- [3-trifluoromethylphenyl] ethanamine (1 .12 g, 4.60 mmol) in N, N-dimethylformamide (15 mL) was added 4- (4,6-dimethoxy [1.3.5] triazin-2-yl) -4-methylmorpholinium chloride water. It was mixed with the Japanese product (953 mg, 4.60 mmol) and stirred at room temperature for 4 days. The reaction solution was mixed with hydrochloric acid (1M) and extracted with ethyl acetate. The organic phase was washed with saturated sodium bicarbonate solution and saturated sodium chloride solution, dried over sodium sulfate, filtered and concentrated to dryness under reduced pressure. Column chromatography purification on silica gel using cyclohexane / ethyl acetate as eluent was performed (gradient: 10% ethyl acetate to 25% ethyl acetate).

  Yield: 603 mg (26% of theory over 2 steps).

HPLC-MS: log P = 4.12; mass (m / z): 493.1 (M + H) ⁺ ; ¹ H NMR (CD ₃ CN) 1.38 (t, 3H), 4.35 (q, 2H) 6.16 (5 folds, 1H), 7.36 (s, 1H), 7.58 (s, 1H), 7.65-7.69 (m, 1H), 7.76-7.79. (M, 1H), 7.87-7.89 (m, 1H), 7.98 (s, 1H), 8.07-8.09 (m, 1H), 8.25 (s, 1H), 10.22 (s, 1H).

Stage 4
6-chloro-N ⁵ -Cyclopropyl-N ² -{2,2,2-trifluoro-1- [3- (trifluoromethyl) phenyl] ethyl} -1H-indole-2,5-dicarboxamide (Compound Ic-24 in Table 3)

６−クロロ−２−（｛２，２，２−トリフルオロ−１−［３−（トリフルオロメチル）フェニル］エチル｝カルバモイル）−１Ｈ−インドール−５−カルボン酸エチル（５９０ｍｇ、１．１８ｍｍｏｌ）のメタノール（８ｍＬ）中溶液を水酸化ナトリウム溶液（１Ｍ、４．２ｍＬ）と混合し、還流下に終夜撹拌した。冷却した溶液を氷冷塩酸（１Ｍ）に加え、沈殿を吸引によって濾過し、少量の水で洗浄し、真空乾燥した。残った固体（３６６ｍｇ）をそれ以上精製せずに次の段階に用いた。

6-Chloro-2-({2,2,2-trifluoro-1- [3- (trifluoromethyl) phenyl] ethyl} carbamoyl) -1H-indole-5-carboxylate (590 mg, 1.18 mmol) Of methanol in methanol (8 mL) was mixed with sodium hydroxide solution (1M, 4.2 mL) and stirred at reflux overnight. The cooled solution was added to ice cold hydrochloric acid (1M) and the precipitate was filtered off with suction, washed with a small amount of water and dried in vacuo. The remaining solid (366 mg) was used in the next step without further purification.

  A portion of the acid thus obtained (121 mg) was dissolved in N, N-dimethylformamide (1.5 mL) and cyclopropylamine (12 mg, 0.20 mmol), HBTU (99 mg, 0.26 mmol) and N- Mix with methylmorpholine (67 mg, 0.66 mmol) and stir at room temperature overnight. The reaction mixture was then concentrated under reduced pressure, taken up in ethyl acetate and washed successively with sodium bicarbonate solution (10%) and saturated sodium chloride solution. The organic phase was dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was chromatographed on preparative HPLC using water / acetonitrile as eluent (gradient = 10% acetonitrile / water to 100% acetonitrile over 43 minutes).

  Yield: 6.4 mg (3% of theory).

HPLC-MS: log P = 3.08; mass (m / z): 504.1 (M + H) ⁺ ; ¹ H NMR (CD ₃ CN) 0.56-0.60 (m, 2H), 0.74- 0.78 (m, 2H), 2.83-2.87 (m, 1H), 6.14 (5-wire, 1H), 6.86 (s, 1H), 7.29 (s, 1H) 7.52 (s, 1H), 7.64-7.68 (m, 1H), 7.76-7.77 (m, 2H), 7.88-7.90 (m, 1H), 7 .97 (s, 1H), 8.08-8.01 (m, 1H), 10.19 (s, 1H).

Synthesis Example 9 (Production of compounds of general formula I-14 according to schemes 6a and 19)
Stage 1
(2E) -3- [4- (N'-hydroxycarbamimidoyl) -3- (trifluoromethyl) phenyl] -N- {2,2,2-trifluoro-1- [3- (trifluoromethyl ) Phenyl] ethyl} acrylamide

実施例Ｉａ−４６からの（２Ｅ）−３−［４−シアノ−３−（トリフルオロメチル）フェニル］−Ｎ−｛２，２，２−トリフルオロ−１−［３−（トリフルオロメチル）フェニル］エチル｝アクリルアミド１．１７ｇ（２．５１ｍｍｏｌ）を最初に、エタノール１１．７ｍＬおよび水２．９ｍＬの混合物に入れ、ヒドロキシルアンモニウムクロライド２０９．６ｍｇ（３．０１ｍｍｏｌ）および炭酸ナトリウム３９９．５ｍｇ（３．７７ｍｍｏｌ）と混合した。反応混合物を１８時間加熱還流し、水と混合した。酢酸エチルで繰り返し抽出した後、合わせた有機相を硫酸マグネシウムで脱水し、溶媒を減圧下に留去し、残留物について、溶離液としてシクロヘキサン／酢酸エチルを用いるシリカゲルを使用するクロマトグラフィーを行った（勾配：０％酢酸エチルから１００％酢酸エチル）。

(2E) -3- [4-Cyano-3- (trifluoromethyl) phenyl] -N- {2,2,2-trifluoro-1- [3- (trifluoromethyl) from Example Ia-46 Phenyl] ethyl} acrylamide 1.17 g (2.51 mmol) is first placed in a mixture of 11.7 mL ethanol and 2.9 mL water, 209.6 mg (3.01 mmol) hydroxylammonium chloride and 399.5 mg (3 .77 mmol). The reaction mixture was heated to reflux for 18 hours and mixed with water. After repeated extraction with ethyl acetate, the combined organic phases were dried over magnesium sulfate, the solvent was distilled off under reduced pressure, and the residue was chromatographed using silica gel with cyclohexane / ethyl acetate as eluent. (Gradient: 0% ethyl acetate to 100% ethyl acetate).

  Yield: 95.0 mg (6.3% of theory).

¹ H NMR (d ₆ -DMSO) δ = 5.87 (s, 2H), 6.15 (m, 1H), 6.93 (d, 1H), 7.55-7.95 (m, 7H) ), 8.05 (d, 1H), 8.18 (s, 1H), 9.60 (d, 1H).

HPLC-MS: log P = 2.55; mass (m / z): 498.1 (M + H) ^<+> .

Stage 2
(2E) -3- [4- (5-Cyclopropyl-1,2,4-oxadiazol-3-yl) -3- (trifluoromethyl) phenyl] -N- {2,2,2-tri Fluoro-1- [3- (trifluoromethyl) phenyl] ethyl} acrylamide (Compound No. Ia-123 in Table 1)

段階１からの（２Ｅ）−３−［４−（Ｎ′−ヒドロキシカルバミミドイル）−３−（トリフルオロメチル）フェニル］−Ｎ−｛２，２，２−トリフルオロ−１−［３−（トリフルオロメチル）フェニル］エチル｝アクリルアミド８０ｍｇ（０．１６ｍｍｏｌ）を最初に、ピリジン２ｍＬに入れ、シクロプロパンカルボニルクロライド１６．７ｍｇ（０．１６ｍｍｏｌ）と室温で混合し、１８時間加熱還流した。ピリジンの大半を減圧下に留去し、残留物を水と混合し、酢酸エチルで抽出した。硫酸マグネシウムで脱水後、溶媒を減圧下に留去し、残留物について、溶離液としてシクロヘキサン／酢酸エチルを用いるシリカゲルでのクロマトグラフィーを行った（勾配：０％酢酸エチルから１００％酢酸エチル）。

(2E) -3- [4- (N'-Hydroxycarbamimidoyl) -3- (trifluoromethyl) phenyl] -N- {2,2,2-trifluoro-1- [3- from step 1 First, 80 mg (0.16 mmol) of (trifluoromethyl) phenyl] ethyl} acrylamide was placed in 2 mL of pyridine, mixed with 16.7 mg (0.16 mmol) of cyclopropanecarbonyl chloride at room temperature, and heated to reflux for 18 hours. Most of the pyridine was distilled off under reduced pressure, and the residue was mixed with water and extracted with ethyl acetate. After dehydration with magnesium sulfate, the solvent was distilled off under reduced pressure and the residue was chromatographed on silica gel using cyclohexane / ethyl acetate as eluent (gradient: 0% ethyl acetate to 100% ethyl acetate).

  Yield: 53.0 mg (58.5% of theory).

¹ H NMR (d ₆ -DMSO) δ = 0.78 (m, 4H), 1.49 (m, 1H), 6,18 (m, 1H), 7.03 (d, 1H), 7.70 -7.80 (m, 3H), 7.87 (m, 2H), 7.91 (m, 1H), 8.04 (d, 1H), 8.18 (s, 1H), 9.60 ( d, 1H).

HPLC-MS: log P = 4.53; mass (m / z): 548.1 (M + H) ^<+> .

Synthesis Example 10 (Production of sulfoxides and sulfones according to Scheme 18)
2-Chloro-N- (1,1-dioxidethietan-3-yl) -4-[(1E) -3-oxo-3-({2,2,2-trifluoro-1- [3- (Trifluoromethyl) phenyl] ethyl} amino) prop-1-en-1-yl] benzamide (Compound No. Ia-166 in Table 1) and 2-chloro-N- (1-oxidethietan-3-yl ) -4-[(1E) -3-oxo-3-({2,2,2-trifluoro-1- [3- (trifluoromethyl) phenyl] ethyl} amino) prop-1-en-1- Yl] benzamide (Compound No. Ia-167 in Table 1)

４−［（１Ｅ）−３−オキソ−３−（｛２，２，２−トリフルオロ−１−［３−（トリフルオロメチル）フェニル］エチル｝−アミノ）プロプ−１−エン−１−イル］−Ｎ−（チエタン−３−イル）−２−（トリフルオロメチル）ベンズアミド（化合物番号Ｉａ−１３０、合成例２と同様にして合成）１００ｍｇ（０．１９ｍｍｏｌ）を最初に、ジクロロメタン５ｍＬに入れ、メタクロロ過安息香酸溶液（含有率：７０％）１１７．８ｍｇ（０．４７ｍｍｏｌ）と混合し、混合物を２０℃で５時間撹拌した。溶液を飽和炭酸水素ナトリウム溶液と混合し、酢酸エチルで繰り返し抽出した。合わせた有機相をチオ硫酸ナトリウム溶液および水の順で洗浄し、硫酸マグネシウムで脱水し、溶媒を減圧下に留去した。残留物について、シリカゲルでのクロマトグラフィーを行った。

4-[(1E) -3-oxo-3-({2,2,2-trifluoro-1- [3- (trifluoromethyl) phenyl] ethyl} -amino) prop-1-en-1-yl ] -N- (thietan-3-yl) -2- (trifluoromethyl) benzamide (Compound No. Ia-130, synthesized in the same manner as in Synthesis Example 2), 100 mg (0.19 mmol) was first put in 5 mL of dichloromethane. , 117.8 mg (0.47 mmol) of a metachloroperbenzoic acid solution (content: 70%), and the mixture was stirred at 20 ° C. for 5 hours. The solution was mixed with saturated sodium bicarbonate solution and extracted repeatedly with ethyl acetate. The combined organic phases were washed with sodium thiosulfate solution and water in this order, dehydrated with magnesium sulfate, and the solvent was distilled off under reduced pressure. The residue was chromatographed on silica gel.

yield:
2-Chloro-N- (1,1-dioxidethietan-3-yl) -4-[(1E) -3-oxo-3-({2,2,2-trifluoro-1- [3- (Trifluoromethyl) phenyl] ethyl} amino) prop-1-en-1-yl] benzamide 28.0 mg (26.1%)
¹ H NMR (d ₆ -DMSO) δ = 4.20 (m, 2H), 4.53 (m, 2H), 4.63 (m, 1H), 6.15 (m, 1H), 6.90 (D, 1H), 7.45-7.85 (m, 5H), 7.95 (m, 1H), 8.05 (s, 1H), 9.28 (d, 1H), 9.50 ( d, 1H).

HPLC-MS: log P = 2.93; mass (m / z): 555.2 (M + H) ^<+> .

2-Chloro-N- (1-oxidethietan-3-yl) -4-[(1E) -3-oxo-3-({2,2,2-trifluoro-1- [3- (trifluoro Methyl) phenyl] ethyl} amino) prop-1-en-1-yl] benzamide 19.0 mg (18.3%)
¹ H NMR (d ₆ -DMSO) δ = 3.20 (m, 2H), 4.20 (m, 2H), 4.38 (m, 1H), 4.63 (m, 2H), 6.15 (M, 1H), 6.90 (d, 1H), 7.45-7.85 (m, 5H), 7.95 (m, 1H), 8.05 (s, 1H), 9.08 ( d, 1H), 9.50 (d, 1H).

HPLC-MS: log P = 2.63; mass (m / z): 539.2 (M + H) ^<+> .

Synthesis Example 11 (Production of compounds of general formulas I and II-1 according to schemes 1 and 7)
Stage 1
N-cyclopropyl-6-iodo-4- (trifluoromethyl) nicotinamide

シクロプロピルアミン（８６２ｍｇ、１５．１ｍｍｏｌ）をジクロロメタン４ｍＬに溶かし、アルゴン下にトリメチルアルミニウムのトルエン中溶液（２Ｍ、７．５５ｍＬ、１５．１ｍｍｏｌ）を滴下混合した。混合物を３０分間撹拌し、ジクロロメタン３ｍＬに溶かした６−ヨード−４−（トリフルオロメチル）ニコチン酸メチル（５００ｍｇ、１．５１ｍｍｏｌ）（ニコチン酸のエステル化によるＪ． Ｍｅｄ． Ｃｈｅｍ．， ２００８， ５１， ３１３３−３１４４と同様の合成）を滴下した。混合物を終夜加熱還流し、冷却して室温とした後、水を注意深く加えた。混合物を酢酸エチルで抽出し、有機相を酒石酸カリウムナトリウム溶液で洗浄し、硫酸マグネシウムで脱水し、濾過し、濾液を減圧下に濃縮した。精製を溶離液のシクロヘキサン／酢酸エチル（ＥＡ）を用いるシリカゲルクロマトグラフィーによって行った（０％ＥＡから３０％ＥＡ）。

Cyclopropylamine (862 mg, 15.1 mmol) was dissolved in 4 mL of dichloromethane, and a solution of trimethylaluminum in toluene (2M, 7.55 mL, 15.1 mmol) was added dropwise under argon. The mixture was stirred for 30 minutes and methyl 6-iodo-4- (trifluoromethyl) nicotinate (500 mg, 1.51 mmol) dissolved in 3 mL of dichloromethane (J. Med. Chem., 2008, 51 by esterification of nicotinic acid). , 3133-3144). The mixture was heated to reflux overnight, cooled to room temperature, and water was carefully added. The mixture was extracted with ethyl acetate and the organic phase was washed with potassium sodium tartrate solution, dried over magnesium sulfate, filtered and the filtrate concentrated under reduced pressure. Purification was performed by silica gel chromatography using eluent cyclohexane / ethyl acetate (EA) (0% EA to 30% EA).

  Yield: 288 mg (53% of theory).

HPLC-MS: log P = 1.92; mass (m / z): 357.0 (M + H) ⁺ ; ¹ H NMR (CD ₃ CN) 0.54-0.59 (m, 2H), 0.72- 0.79 (m, 2H), 2.79-2.82 (m, 1H), 7.07 (brs, 1H), 8.11 (s, 1H), 8.48 (s, 1H).

Stage 2
(2E) -3- [5- (Cyclopropylcarbamoyl) -4- (trifluoromethyl) pyridin-2-yl] acrylic acid

Ｎ−シクロプロピル−６−ヨード−４−（トリフルオロメチル）ニコチンアミド（１２５ｍｇ、０．３４ｍｍｏｌ）および（２Ｅ）−３−（４，４，５，５−テトラメチル−１，３，２−ジオキサボロラン−２−イル）アクリル酸エチル（９３ｍｇ、０．４１ｍｍｏｌ）を１，４−ジオキサン２ｍＬに溶かし、アルゴン下に炭酸ナトリウム（１８０ｍｇ、１．７２ｍｍｏｌ）およびビス（トリシクロヘキシルホスフィン）・二塩化パラジウム（ＩＩ）と混合した。反応混合物をマイクロ波装置（ＣＥＭ Ｄｉｓｃｏｖｅｒ）において１２０℃（８０Ｗ）で１０分間加熱した。次に、反応混合物を珪藻土で濾過し、濾液を酢酸エチルに取り、塩酸（１Ｍ）で洗浄し、硫酸マグネシウムで脱水し、濾過し、減圧下に濃縮した。残留物をエタノール１．５ｍＬに取り、水酸化ナトリウム溶液（１Ｍ）と混合し、室温で終夜撹拌した。次に、反応混合物を氷冷した希塩酸に加え、酢酸エチルで抽出した。有機相を硫酸ナトリウムで脱水し、濾過し、減圧下に濃縮して乾固させた。

N-cyclopropyl-6-iodo-4- (trifluoromethyl) nicotinamide (125 mg, 0.34 mmol) and (2E) -3- (4,4,5,5-tetramethyl-1,3,2- Dioxaborolan-2-yl) ethyl acrylate (93 mg, 0.41 mmol) was dissolved in 2 mL of 1,4-dioxane, and sodium carbonate (180 mg, 1.72 mmol) and bis (tricyclohexylphosphine) .palladium dichloride ( Mixed with II). The reaction mixture was heated in a microwave apparatus (CEM Discover) at 120 ° C. (80 W) for 10 minutes. The reaction mixture was then filtered through diatomaceous earth and the filtrate was taken up in ethyl acetate, washed with hydrochloric acid (1M), dried over magnesium sulfate, filtered and concentrated under reduced pressure. The residue was taken up in 1.5 mL of ethanol, mixed with sodium hydroxide solution (1M) and stirred at room temperature overnight. Next, the reaction mixture was added to ice-cooled dilute hydrochloric acid and extracted with ethyl acetate. The organic phase was dried over sodium sulfate, filtered and concentrated to dryness under reduced pressure.

  Yield: 72 mg (70% of theory).

HPLC-MS: log P = 1.26; mass (m / z): 301.1 (M + H) ⁺ ; ¹ H NMR (CD ₃ CN) 0.56-0.58 (m, 2H), 0.76- 0.79 (m, 2H), 2.80-2.85 (m, 1H), 6.96 (d, 1H), 7.08 (brs, 1H), 7.69 (d, 1H), 7 .87 (s, 1H), 8.74 (s, 1H), 9.5 (brs, 1H).

Stage 3
N-cyclopropyl-6-[(1E) -3-oxo-3-({2,2,2-trifluoro-1- [3- (trifluoromethyl) phenyl] ethyl} amino) -prop-1- En-1-yl] -4- (trifluoromethyl) nicotinamide (Compound No. If-2 in Table 6)

（２Ｅ）−３−［５−（シクロプロピルカルバモイル）−４−（トリフルオロメチル）ピリジン−２−イル］アクリル酸（６１ｍｇ、０．２０ｍｍｏｌ）および２，２，２−トリフルオロ−１−［３−トリフルオロメチルフェニル］エタンアミン（４６ｍｇ、０．１９ｍｍｏｌ）を最初に、Ｎ，Ｎ−ジメチルホルムアミドに入れ、ＨＢＴＵ（７２ｍｇ、０．１９ｍｍｏｌ）およびＮ−メチルモルホリン（５７ｍｇ、０．５７ｍｍｏｌ）と混合し、室温で終夜撹拌した。次に、反応混合物を減圧下に濃縮し、酢酸エチルに取り、炭酸水素ナトリウム溶液（１０％）および飽和塩化ナトリウム溶液の順で洗浄した。有機相を硫酸ナトリウムで脱水し、濾過し、減圧下に濃縮した。残留物について、溶離液として水／アセトニトリルを用いる分取ＨＰＬＣでのクロマトグラフィーを行った（勾配＝４３分かけて１０％アセトニトリル／水から１００％アセトニトリル）。

(2E) -3- [5- (Cyclopropylcarbamoyl) -4- (trifluoromethyl) pyridin-2-yl] acrylic acid (61 mg, 0.20 mmol) and 2,2,2-trifluoro-1- [ 3-Trifluoromethylphenyl] ethanamine (46 mg, 0.19 mmol) is first placed in N, N-dimethylformamide and mixed with HBTU (72 mg, 0.19 mmol) and N-methylmorpholine (57 mg, 0.57 mmol). And stirred at room temperature overnight. The reaction mixture was then concentrated under reduced pressure, taken up in ethyl acetate and washed successively with sodium bicarbonate solution (10%) and saturated sodium chloride solution. The organic phase was dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was chromatographed on preparative HPLC using water / acetonitrile as eluent (gradient = 10% acetonitrile / water to 100% acetonitrile over 43 minutes).

  Yield: 17 mg (16% of theory).

HPLC-MS: log P = 3.27; mass (m / z): 526.1 (M + H) ⁺ ; ¹ H NMR (CD ₃ CN) 0.56-0.58 (m, 2H), 0.76- 0.78 (m, 2H), 2.81-2.85 (m, 1H), 6.01 (5-wire, 1H), 7.08 (s, 1H), 7.28 (d, 1H) 7.65-7.68 (m, 2H), 7.76-7.81 (m, 3H).

Synthesis Example 12 (Production of compounds of general formulas I-16 and I-17 according to schemes 4, 6c and 17)
Stage 1
Ethyl 6-chloro-1-methyl-2-({2,2,2-trifluoro-1- [3- (trifluoromethyl) phenyl] ethyl} carbamoyl) -1H-indole-5-carboxylate

６−クロロ−２−（｛２，２，２−トリフルオロ−１−［３−（トリフルオロメチル）フェニル］エチル｝カルバモイル）−１Ｈ−インドール−５−カルボン酸エチル（１．３０ｇ、２．６３ｍｍｏｌ）（合成例８、段階３）および炭酸カリウムを最初に、アセトニトリル（３９ｍＬ）に入れ、ヨードメタン（５６１ｍｇ、３．９５ｍｍｏｌ）と混合した。反応混合物を終夜加熱還流した。冷却して室温とした後、混合物を減圧下に濃縮して乾固させ、残留物を酢酸エチルに取り、水で洗浄した。有機相を硫酸ナトリウムで脱水し、濾過し、減圧下に濃縮して乾固させた。

Ethyl 6-chloro-2-({2,2,2-trifluoro-1- [3- (trifluoromethyl) phenyl] ethyl} carbamoyl) -1H-indole-5-carboxylate (1.30 g, 2. 63 mmol) (Synthesis Example 8, Step 3) and potassium carbonate were first taken in acetonitrile (39 mL) and mixed with iodomethane (561 mg, 3.95 mmol). The reaction mixture was heated to reflux overnight. After cooling to room temperature, the mixture was concentrated to dryness under reduced pressure and the residue was taken up in ethyl acetate and washed with water. The organic phase was dried over sodium sulfate, filtered and concentrated to dryness under reduced pressure.

  Yield: 1.14 g (85% of theory).

HPLC-MS: log P = 4.74; mass (m / z): 507.2 (M + H) ⁺ ; ¹ H NMR (CD ₃ CN) 1.38 (t, 3H), 3.93 (s, 3H) 4.35 (q, 2H), 6.13 (5-wire, 1H), 7.25 (s, 1H), 7.59 (s, 1H), 7.65-7.69 (m, 1H) ), 7.77-7.79 (m, 1H), 7.88-7.90 (m, 1H), 7.98 (s, 1H), 8.08-8.11 (m, 1H), 8.21 (s, 1H).

Stage 2
N ⁵ -Allyl-6-chloro-1-methyl-N ² -{2,2,2-trifluoro-1- [3- (trifluoromethyl) phenyl] ethyl} -1H-indole-2,5-dicarboxamide (Compound No. Ic-32 in Table 3)

アリルアミン（１５６ｍｇ、２．７３ｍｍｏｌ）をジクロロメタン３ｍＬに溶かし、アルゴン下にトリメチルアルミニウムのトルエン中溶液（２Ｍ、１．３７ｍＬ、２．７３ｍｍｏｌ）を滴下混合した。混合物を３０分間撹拌し、６−クロロ−１−メチル−２−（｛２，２，２−トリフルオロ−１−［３−（トジクロロメタン３ｍＬに溶かしたリフルオロメチル）フェニル］エチル｝カルバモイル）−１Ｈ−インドール−５−カルボン酸エチル（１６５ｍｇ、０．２７ｍｍｏｌ）を滴下した。混合物を終夜加熱還流し、冷却して室温とした後、水を注意深く加えた。混合物を酢酸エチルで抽出し、有機相を酒石酸カリウムナトリウム溶液で洗浄し、硫酸マグネシウムで脱水し、濾過し、濾液を減圧下に濃縮した。精製を溶離液のシクロヘキサン／酢酸エチル（ＥＡ）を用いるシリカゲルクロマトグラフィーによって行った（０％ＥＡから３０％ＥＡ）。

Allylamine (156 mg, 2.73 mmol) was dissolved in 3 mL of dichloromethane, and a solution of trimethylaluminum in toluene (2 M, 1.37 mL, 2.73 mmol) was added dropwise and mixed under argon. The mixture was stirred for 30 minutes and 6-chloro-1-methyl-2-({2,2,2-trifluoro-1- [3- (trifluoromethyl) phenyl] ethyl} carbamoyl dissolved in 3 mL of dichloromethane) Ethyl 1H-indole-5-carboxylate (165 mg, 0.27 mmol) was added dropwise. The mixture was heated to reflux overnight, cooled to room temperature, and water was carefully added. The mixture was extracted with ethyl acetate and the organic phase was washed with potassium sodium tartrate solution, dried over magnesium sulfate, filtered and the filtrate concentrated under reduced pressure. Purification was performed by silica gel chromatography using eluent cyclohexane / ethyl acetate (EA) (0% EA to 30% EA).

  Yield: 74 mg (52% of theory).

HPLC-MS: log P = 3.68; mass (m / z): 518.2 (M + H) ⁺ ; ¹ H NMR (d ₆ -DMSO) 3.88-3.90 (m, 2H), 3.95 (S, 3H), 5.11-5.14 (m, 1H), 5.26-5.29 (m, 1H), 5.87-5.94 (m, 1H), 6.30 (5 Double line, 1H), 7.42 (s, 1H), 7.71-7.73 (m, 1H), 7.78 (s, 1H), 7.82-7.83 (m, 2H), 8.07-8.08 (m, 1H), 8.22 (s, 1H), 8.56-8.58 (m, 1H) 9.79 (d, 1H).

Synthesis Example 13 (Production of compounds of general formula I-15 according to schemes 6b and 20)
Stage 1
2-Chloro-N-cyclopropyl-4-iodobenzamide

２−クロロ−４−ヨード安息香酸（３．３１ｇ、１１．７ｍｍｏｌ）を酢酸エチル（２３ｍＬ）に溶かし、Ｎ，Ｎ−ジメチルホルムアミド１滴および塩化チオニル（６．９６ｇ、５９．０ｍｍｏｌ）と混合し、終夜加熱還流した。冷却した懸濁液を減圧下に濃縮し、ジクロロメタン（６０ｍＬ）に取った。溶液を冷却して０℃とし、ピリジン（９２５ｍｇ、１１．７ｍｍｏｌ）およびシクロプロピルアミン（６６８ｍｇ、１１．７ｍｍｏｌ）を滴下した。反応混合物を昇温させて室温とし、終夜撹拌した。それを塩酸（１Ｍ）で洗浄し、硫酸ナトリウムで脱水し、濾過し、減圧下に濃縮して乾固させた。

2-Chloro-4-iodobenzoic acid (3.31 g, 11.7 mmol) is dissolved in ethyl acetate (23 mL) and mixed with 1 drop of N, N-dimethylformamide and thionyl chloride (6.96 g, 59.0 mmol). , Heated to reflux overnight. The cooled suspension was concentrated under reduced pressure and taken up in dichloromethane (60 mL). The solution was cooled to 0 ° C. and pyridine (925 mg, 11.7 mmol) and cyclopropylamine (668 mg, 11.7 mmol) were added dropwise. The reaction mixture was warmed to room temperature and stirred overnight. It was washed with hydrochloric acid (1M), dried over sodium sulfate, filtered and concentrated to dryness under reduced pressure.

  Yield: 3.06 g (81% of theory).

HPLC-MS: log P = 2.13; mass (m / z): 321.9 (M + H) ⁺ ; ¹ H NMR (CD ₃ CN) 0.53-0.57 (m, 2H), 0.72- 0.77 (m, 2H), 2.77-2.83 (m, 1H), 6.87 (brs, 1H), 7.16 (d, 1H), 7.71 (d, 1H), 7 .84 (s, 1H).

Stage 2
2-Chloro-N-cyclopropyl-4- [3-oxo-3-({2,2,2-trifluoro-1- [3- (trifluoromethyl) phenyl] ethyl} amino) prop-1-yne -1-yl] benzamide

２−クロロ−Ｎ−シクロプロピル−４−ヨードベンズアミド（１．０ｇ、３．１１ｍｍｏｌ）およびプロピオール酸（２２２ｍｇ、３．１１ｍｍｏｌ）をＮ，Ｎ−ジメチルホルムアミド（１．２ｍＬ）に溶かし、冷却して０℃とした。次に、ビス（トリフェニルホスフィン）パラジウム（ＩＩ）ジクロライド（４３ｍｇ、０．０６ｍｍｏｌ）およびヨウ化銅（Ｉ）（２３ｍｇ、０．１２ｍｍｏｌ）を加え、混合物を冷却して−１０℃とした。ジイソプロピルアミン（７８６ｍｇ、７．７７ｍｍｏｌ）を加えた後、混合物をゆっくり昇温させて室温とし、終夜撹拌した。反応混合物を酢酸エチルで希釈し、塩酸（２Ｍ）および飽和塩化ナトリウム溶液の順で洗浄し、硫酸マグネシウムで脱水し、濾過し、減圧下に濃縮して乾固させた。残留物をＮ，Ｎ−ジメチルホルムアミド（１ｍＬ）に溶かし、４−（４，６−ジメトキシ［１．３．５］トリアジン−２−イル）−４−メチルモルホリニウムクロライド水和物（９７３ｍｇ、３．５２ｍｍｏｌ）および２，２，２−トリフルオロ−１−［３−トリフルオロメチルフェニル］エタンアミン（７８０ｍｇ、３．２０ｍｍｏｌ）と混合し、室温で終夜撹拌した。反応溶液を塩酸（１Ｍ）と混合し、酢酸エチルで抽出した。有機相を飽和炭酸水素ナトリウム溶液および飽和塩化ナトリウム溶液で洗浄し、硫酸ナトリウムで脱水し、濾過し、減圧下に濃縮して乾固させた。残留物を、溶離液のシクロヘキサン／酢酸エチル（ＥＡ）を用いるシリカゲルクロマトグラフィーによって精製した（０％ＥＡから４０％ＥＡ）。

2-Chloro-N-cyclopropyl-4-iodobenzamide (1.0 g, 3.11 mmol) and propiolic acid (222 mg, 3.11 mmol) were dissolved in N, N-dimethylformamide (1.2 mL) and cooled. The temperature was 0 ° C. Next, bis (triphenylphosphine) palladium (II) dichloride (43 mg, 0.06 mmol) and copper (I) iodide (23 mg, 0.12 mmol) were added and the mixture was cooled to −10 ° C. After adding diisopropylamine (786 mg, 7.77 mmol), the mixture was slowly warmed to room temperature and stirred overnight. The reaction mixture was diluted with ethyl acetate, washed sequentially with hydrochloric acid (2M) and saturated sodium chloride solution, dried over magnesium sulfate, filtered and concentrated to dryness under reduced pressure. The residue was dissolved in N, N-dimethylformamide (1 mL) and 4- (4,6-dimethoxy [1.3.5] triazin-2-yl) -4-methylmorpholinium chloride hydrate (973 mg, 3.52 mmol) and 2,2,2-trifluoro-1- [3-trifluoromethylphenyl] ethanamine (780 mg, 3.20 mmol) and stirred at room temperature overnight. The reaction solution was mixed with hydrochloric acid (1M) and extracted with ethyl acetate. The organic phase was washed with saturated sodium bicarbonate solution and saturated sodium chloride solution, dried over sodium sulfate, filtered and concentrated to dryness under reduced pressure. The residue was purified by silica gel chromatography using eluent cyclohexane / ethyl acetate (EA) (0% EA to 40% EA).

  Yield: 462 mg (30% of theory).

HPLC-MS: log P = 3.34; mass (m / z): 489.0 (M + H) ⁺ ; ¹ H NMR (CD ₃ CN) 0.57-0.59 (m, 2H), 0.74- 0.78 (m, 2H), 2.79-2.86 (m, 1H), 5.94 (5-wire, 1H), 6.93 (s, 1H), 7.45-7.47 ( m, 1H), 7.55-7.57 (m, 1H), 7.65-7.69 (m, 2H), 7.74-7.78 (m, 1H), 7.90 (s, 1H), 8.30 (d, 1H).

Stage 3
2-Chloro-N-cyclopropyl-4-[(1Z) -3-oxo-3-({2,2,2-trifluoro-1- [3- (trifluoromethyl) phenyl] ethyl} -amino) Prop-1-en-1-yl] benzamide (Compound No. Ig-1 in Table 7)

２−クロロ−Ｎ−シクロプロピル−４−［３−オキソ−３−（｛２，２，２−トリフルオロ−１−［３−（トリフルオロメチル）フェニル］エチル｝アミノ）−プロプ−１−イン−１−イル］ベンズアミド（１１０ｍｇ、０．２０ｍｍｏｌ）、キノリン（１０ｍｇ、０．０７ｍｍｏｌ）およびパラジウム／炭酸カルシウム（５％Ｐｄ；１０ｍｇ）をメタノールに懸濁させ、４日間撹拌し、その途中でパラジウム／炭酸カルシウムを２４時間ごとに再度添加した（１０ｍｇを３回）。次に、反応混合物を珪藻土で濾過し、濾液を減圧下に濃縮して乾固させた。残留物を、溶離液のシクロヘキサン／酢酸エチル（ＥＡ）を用いるシリカゲルクロマトグラフィーによって精製した（０％ＥＡから５０％ＥＡ）。

2-Chloro-N-cyclopropyl-4- [3-oxo-3-({2,2,2-trifluoro-1- [3- (trifluoromethyl) phenyl] ethyl} amino) -prop-1- In-1-yl] benzamide (110 mg, 0.20 mmol), quinoline (10 mg, 0.07 mmol) and palladium / calcium carbonate (5% Pd; 10 mg) were suspended in methanol and stirred for 4 days. Palladium / calcium carbonate was added again every 24 hours (3 times 10 mg). The reaction mixture was then filtered through diatomaceous earth and the filtrate was concentrated to dryness under reduced pressure. The residue was purified by silica gel chromatography using eluent cyclohexane / ethyl acetate (EA) (0% EA to 50% EA).

  Yield: 72 mg (70% of theory).

HPLC-MS: log P = 3.06; mass (m / z): 489.1 (M−H) ⁻ ; ¹ H NMR (CD ₃ CN) 0.54-0.57 (m, 2H), 0. 73-0.76 (m, 2H), 2.79-2.83 (m, 1H), 5.93 (5-fold, 1H), 6.17 (d, 1H), 6.81 (d, 1H), 6.87 (s, 1H), 7.27-7.29 (m, 1H), 7.36-7.37 (m, 1H), 7.57 (s, 1H), 7.61 -7.64 (m, 1H), 7.70-7.71 (m, 1H), 7.74-7.76 (m, 1H), 7.82-7.86 (m, 2H).

Synthesis Example 14 (Production of compounds of general formulas I and III-1 according to schemes 10a and 21)
Stage 1
2,2-Difluoro-1- [3- (trifluoromethyl) phenyl] propan-1-one

２−プロピルマグネシウムクロライドのＴＨＦ（１．３Ｍ、７．５ｍＬ）中溶液を冷却して−１５℃とし、１−ヨード−３−（トリフルオロメチル）ベンゼン（２．８０ｇ、１０．２ｍｍｏｌ）と混合した。反応混合物を−１５℃で１時間撹拌し、昇温させて室温とし、２，２−ジフルオロ−Ｎ−メトキシ−Ｎ−メチルプロパンアミドの溶液（１．４３ｇ、９．３５ｍｍｏｌ；Ｓｙｎｔｈ． Ｃｏｍｍ． ２００８（３８）， １９４０−１９４５に従って製造）を滴下混合し、室温で終夜撹拌した。次に、混合物を氷冷した希塩酸に加え、酢酸エチルで抽出した。合わせた有機相を硫酸ナトリウムで脱水し、減圧下に濃縮した。残留物を、溶離液のシクロヘキサン／酢酸エチル（ＥＡ）を用いるシリカゲルクロマトグラフィーによって精製した（０％ＥＡから３０％ＥＡ）。

A solution of 2-propylmagnesium chloride in THF (1.3 M, 7.5 mL) was cooled to −15 ° C. and mixed with 1-iodo-3- (trifluoromethyl) benzene (2.80 g, 10.2 mmol). did. The reaction mixture was stirred at −15 ° C. for 1 hour, warmed to room temperature, and a solution of 2,2-difluoro-N-methoxy-N-methylpropanamide (1.43 g, 9.35 mmol; Synth. Comm. 2008). (38), produced according to 1940-1945) was added dropwise and stirred at room temperature overnight. Next, the mixture was added to ice-cooled dilute hydrochloric acid and extracted with ethyl acetate. The combined organic phases were dried over sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel chromatography using eluent cyclohexane / ethyl acetate (EA) (0% EA to 30% EA).

  Yield: 1.19 g (53% of theory).

HPLC-MS: log P = 3.61; ¹ H NMR (CD ₃ CN) 1.93 (t, 3H), 7.78 (t, 1H), 8.02 (d, 1H), 8.31-8 .34 (m, 2H).

Stage 2
2-Chloro-N-cyclopropyl-4-[(1E) -3-({2,2-difluoro-1- [3- (trifluoromethyl) phenyl] propyl} amino) -3-oxoprop-1-ene -1-yl] benzamide (Compound No. 1d-1 in Table 4)

２，２−ジフルオロ−１−［３−（トリフルオロメチル）フェニル］プロパン−１−オン（１．１９ｇ、４．９９ｍｍｏｌ）のエタノール（１５ｍＬ）中溶液を水（１．５ｍＬ）、ヒドロキシルアミン塩酸塩（６９５ｍｇ、１０．０ｍｍｏｌ）および酢酸ナトリウム（９２２ｍｇ、１１．２ｍｍｏｌ）と混合し、７５℃で２１時間撹拌した。冷却して室温としておいた混合物を減圧下に濃縮し、塩酸（１Ｍ）に取り、酢酸エチルで抽出した。合わせた有機相を硫酸ナトリウムで脱水し、減圧下に濃縮した。残った固体をテトラヒドロフラン（１５ｍＬ）に溶かし、アルゴン下に冷却して０℃とした。次に、水素化リチウムアルミニウム（３６２ｍｇ、９．０８ｍｍｏｌ）を加え、混合物を最初に昇温させて室温とし、次に２時間加熱還流した。次に、反応混合物を冷却して０℃とし、最初に飽和塩化アンモニウム溶液と混合し、水酸化ナトリウム溶液（１Ｍ）で希釈し、酢酸エチルで抽出した。有機相を硫酸ナトリウムで脱水し、濾過し、減圧下に濃縮して乾固させた。残留物をＮ，Ｎ−ジメチルホルムアミド（７．５ｍＬ）に溶かし、（２Ｅ）−３−［３−クロロ−４−（シクロプロピルカルバモイル）フェニル］アクリル酸（２５０ｍｇ、０．９４ｍｍｏｌ）および４−（４，６−ジメトキシ［１．３．５］トリアジン−２−イル）−４−メチルモルホリニウムクロライド水和物（２７０ｍｇ、０．９７ｍｍｏｌ）の順で混合し、室温で終夜撹拌した。反応溶液を塩酸（１Ｍ）と混合し、酢酸エチルで抽出した。有機相を飽和炭酸水素ナトリウム溶液および飽和塩化ナトリウム溶液で洗浄し、硫酸ナトリウムで脱水し、濾過し、減圧下に濃縮して乾固させた。残留物について、溶離液として水／アセトニトリルを用いる分取ＨＰＬＣでのクロマトグラフィーを行った（勾配＝４３分かけて１０％アセトニトリル／水から１００％アセトニトリル）。

A solution of 2,2-difluoro-1- [3- (trifluoromethyl) phenyl] propan-1-one (1.19 g, 4.99 mmol) in ethanol (15 mL) was added to water (1.5 mL), hydroxylamine hydrochloride. Salt (695 mg, 10.0 mmol) and sodium acetate (922 mg, 11.2 mmol) were mixed and stirred at 75 ° C. for 21 hours. The mixture, cooled to room temperature, was concentrated under reduced pressure, taken up in hydrochloric acid (1M) and extracted with ethyl acetate. The combined organic phases were dried over sodium sulfate and concentrated under reduced pressure. The remaining solid was dissolved in tetrahydrofuran (15 mL) and cooled to 0 ° C. under argon. Next, lithium aluminum hydride (362 mg, 9.08 mmol) was added and the mixture was first warmed to room temperature and then heated to reflux for 2 hours. The reaction mixture was then cooled to 0 ° C., first mixed with saturated ammonium chloride solution, diluted with sodium hydroxide solution (1M) and extracted with ethyl acetate. The organic phase was dried over sodium sulfate, filtered and concentrated to dryness under reduced pressure. The residue was dissolved in N, N-dimethylformamide (7.5 mL) and (2E) -3- [3-chloro-4- (cyclopropylcarbamoyl) phenyl] acrylic acid (250 mg, 0.94 mmol) and 4- ( 4,6-Dimethoxy [1.3.5] triazin-2-yl) -4-methylmorpholinium chloride hydrate (270 mg, 0.97 mmol) was mixed in this order and stirred at room temperature overnight. The reaction solution was mixed with hydrochloric acid (1M) and extracted with ethyl acetate. The organic phase was washed with saturated sodium bicarbonate solution and saturated sodium chloride solution, dried over sodium sulfate, filtered and concentrated to dryness under reduced pressure. The residue was chromatographed on preparative HPLC using water / acetonitrile as eluent (gradient = 10% acetonitrile / water to 100% acetonitrile over 43 minutes).

  Yield: 108 mg (4% of theory).

HPLC-MS: log P = 3.04; mass (m / z): 487.1 (M + H) ⁺ ; ¹ H NMR (CD ₃ CN) 0.56-0.59 (m, 2H), 0.73- 0.77 (m, 2H), 0.92 (t, 3H), 2.81-2.84 (m, 1H), 4.91-4.92 (m, 1H), 6.65 (d, 1H), 6.93 (s, 1H), 7.16-7.17 (m, 1H), 7.39-7.42 (m, 2H), 7.47-7.65 (m, 6H) .

５−ブロモインダン−１−アミン１６ｇ（７５．４ｍｍｏｌ）、水酸化ナトリウム１２．８ｇ（３２０ｍｍｏｌ）の水溶液およびＴＨＦ ２００ｍＬの混合物を、０℃でジ−ｔｅｒｔ−ブチルジカーボネート３２．９ｇ（１５１ｍｍｏｌ）のＴＨＦ中溶液と混合し、０℃で変換が完了するまで撹拌した。抽出後処理およびクロマトグラフィー精製によって、ｔｅｒｔ−ブチル（５−ブロモ−２，３−ジヒドロ−１Ｈ−インデン−１−イル）カーバメート１８ｇ（５７．７ｍｍｏｌ）（７７％）を得た。 Synthesis Example 15 (Production of compounds of general formulas I and II according to scheme 12c)
Stage 1
tert-Butyl (5-bromo-2,3-dihydro-1H-inden-1-yl) carbamate

A mixture of 16 g (75.4 mmol) of 5-bromoindan-1-amine, 12.8 g (320 mmol) of sodium hydroxide and 200 mL of THF was mixed with 32.9 g (151 mmol) of di-tert-butyl dicarbonate at 0 ° C. Mix with the solution in THF and stir at 0 ° C. until conversion is complete. Extraction workup and chromatographic purification gave 18 g (57.7 mmol) (77%) of tert-butyl (5-bromo-2,3-dihydro-1H-inden-1-yl) carbamate.

Stage 2
(2E) -3- {1-[(tert-butoxycarbonyl) amino] -2,3-dihydro-1H-inden-5-yl} methyl acrylate

ｔｅｒｔ−ブチル（５−ブロモ−２，３−ジヒドロ−１Ｈ−インデン−１−イル）カーバメート２５ｇ（８０．１ｍｍｏｌ）、トリス（２−メチルフェニル）ホスフィン９７５ｍｇ（３．２０ｍｍｏｌ）、酢酸パラジウム（ＩＩ）１７９ｍｇ（７９７μｍｏｌ）およびアクリル酸メチル８．９ｇ（１０３ｍｍｏｌ）のトリエチルアミン（１５０ｍＬ）中混合物を１５０℃で５時間撹拌した。沈殿を濾過し、クロマトグラフィー精製を行って、（２Ｅ）−３−｛１−［（ｔｅｒｔ−ブトキシカルボニル）アミノ］−２，３−ジヒドロ−１Ｈ−インデン−５−イル｝アクリル酸メチル１９ｇ（５９．９ｍｍｏｌ）（７５％）を得た。

tert-butyl (5-bromo-2,3-dihydro-1H-inden-1-yl) carbamate 25 g (80.1 mmol), tris (2-methylphenyl) phosphine 975 mg (3.20 mmol), palladium (II) acetate A mixture of 179 mg (797 μmol) and 8.9 g (103 mmol) of methyl acrylate in triethylamine (150 mL) was stirred at 150 ° C. for 5 hours. The precipitate was filtered and chromatographically purified to give 19 g of methyl (2E) -3- {1-[(tert-butoxycarbonyl) amino] -2,3-dihydro-1H-inden-5-yl} acrylate ( 59.9 mmol) (75%).

Stage 3
(2E) -3- {1-[(tert-Butoxycarbonyl) amino] -2,3-dihydro-1H-inden-5-yl} acrylic acid

（２Ｅ）−３−｛１−［（ｔｅｒｔ−ブトキシカルボニル）アミノ］−２，３−ジヒドロ−１Ｈ−インデン−５−イル｝アクリル酸メチル１７ｇ（５３．６ｍｍｏｌ）を、希水酸化ナトリウム溶液３００ｍＬ中で１時間加熱還流し、得られた沈殿を濾過し、ジエチルエーテルで洗浄し、真空乾燥した。これによって、（２Ｅ）−３−｛１−［（ｔｅｒｔ−ブトキシカルボニル）アミノ］−２，３−ジヒドロ−１Ｈ−インデン−５−イル｝アクリル酸（８４％）１３．６ｇ（４４．８ｍｍｏｌ）が得られる。

(2E) -3- {1-[(tert-butoxycarbonyl) amino] -2,3-dihydro-1H-inden-5-yl} methyl acrylate (17 g, 53.6 mmol) was added to a diluted sodium hydroxide solution (300 mL) The mixture was heated to reflux for 1 hour and the resulting precipitate was filtered, washed with diethyl ether and dried in vacuo. This gave (2E) -3- {1-[(tert-butoxycarbonyl) amino] -2,3-dihydro-1H-inden-5-yl} acrylic acid (84%) 13.6 g (44.8 mmol) Is obtained.

¹ H NMR (400 MHz, d ₆ -DMSO) δ = 1.43 (s, 9H), 1.82 (m, 1H), 2.35 (m, 1H), 2.77 (m, 1H), 2 .89 (m, 1H), 4.98 (m, 1H), 6.46 (d, 1H), 7.21 (t, 1H), 7.48 (d, 1H), 7.52 (s, 1H), 7.56 (d, 1H), 12.22 (brs, 1H).

HPLC-MS: log P = 2.47; mass (m / z): 248.1 (M-tBu) ^<+> .

Stage 4
tert-butyl {5-[(1E) -3-oxo-3-({2,2,2-trifluoro-1- [3- (trifluoromethyl) phenyl] ethyl} amino) prop-1-ene- 1-yl] -2,3-dihydro-1H-inden-1-yl} carbamate

（２Ｅ）−３−｛１−［（ｔｅｒｔ−ブトキシカルボニル）アミノ］−２，３−ジヒドロ−１Ｈ−インデン−５−イル｝アクリル酸１．５ｇ（４．９５ｍｍｏｌ）および２，２，２−トリフルオロ−１−［３−（トリフルオロメチル）フェニル］エタンアミン１．２ｇ（４．９５ｍｍｏｌ）をＤＭＦ １００ｍＬに溶かし、４−（４，６−ジメトキシ−１，３，５−トリアジン−２−イル）−４−メチルモルホリン−４−イウムクロライド１．５ｇ（５．４４ｍｍｏｌ）を加え、反応混合物を加熱して５０℃として終夜経過させた。反応溶液を酢酸エチルで希釈し、飽和ＮａＨＣＯ_３溶液、１Ｎ塩酸および飽和塩化ナトリウム溶液で洗浄し、硫酸ナトリウムで脱水し、濾過し、濃縮した。クロマトグラフィー精製によって、ｔｅｒｔ−ブチル｛５−［（１Ｅ）−３−オキソ−３−（｛２，２，２−トリフルオロ−１−［３−（トリフルオロメチル）フェニル］エチル｝アミノ）プロプ−１−エン−１−イル］−２，３−ジヒドロ−１Ｈ−インデン−１−イル｝カーバメート２．３ｇ（４．４５ｍｍｏｌ）（８７％）を得た。

(2E) -3- {1-[(tert-Butoxycarbonyl) amino] -2,3-dihydro-1H-inden-5-yl} acrylic acid 1.5 g (4.95 mmol) and 2,2,2- Trifluoro-1- [3- (trifluoromethyl) phenyl] ethanamine 1.2 g (4.95 mmol) was dissolved in 100 mL of DMF, and 4- (4,6-dimethoxy-1,3,5-triazin-2-yl was dissolved. ) -4-methylmorpholine-4-ium chloride 1.5 g (5.44 mmol) was added and the reaction mixture was heated to 50 ° C. overnight. The reaction solution was diluted with ethyl acetate, washed with saturated NaHCO ₃ solution, 1N hydrochloric acid and saturated sodium chloride solution, dried over sodium sulfate, filtered and concentrated. Chromatographic purification gave tert-butyl {5-[(1E) -3-oxo-3-({2,2,2-trifluoro-1- [3- (trifluoromethyl) phenyl] ethyl} amino) prop -1-en-1-yl] -2,3-dihydro-1H-inden-1-yl} carbamate 2.3 g (4.45 mmol) (87%) was obtained.

¹ H NMR (400 MHz, d ₆ -DMSO) δ = 1.43 (s, 9H), 1.83 (m, 1H), 2.37 (m, 1H), 2.78 (m, 1H), 2 .91 (m, 1H), 4.99 (m, 1H), 6.14 (p, 1H), 6.78 (d, 1H), 7.23 (m, 2H), 7.43 (m, 2H), 7.53 (d, 1H), 7.71 (t, 1H), 7.80 (d, 1H), 7.94 (d, 1H), 8.04 (s, 1H), 9. 39 ppm (d, 1H).

HPLC-MS: log P = 4.44; mass (m / z): 529.2 (M + H) ^<+> .

Stage 5
(2E) -3- (1-Amino-2,3-dihydro-1H-inden-5-yl) -N- {2,2,2-trifluoro-1- [3- (trifluoromethyl) phenyl] Ethyl} acrylamide

ｔｅｒｔ−ブチル｛５−［（１Ｅ）−３−オキソ−３−（｛２，２，２−トリフルオロ−１−［３−（トリフルオロメチル）フェニル］エチル｝アミノ）プロプ−１−エン−１−イル］−２，３−ジヒドロ−１Ｈ−インデン−１−イル｝カーバメート２．２ｇをジオキサン４０ｍＬに溶かし、半飽和塩酸１０ｍＬと混合し、室温で終夜撹拌した。反応混合物を水と混合し、酢酸エチルで抽出した。合わせた有機相を硫酸ナトリウムで脱水し、濾過し、濃縮した。これによって、（２Ｅ）−３−（１−アミノ−２，３−ジヒドロ−１Ｈ−インデン−５−イル）−Ｎ−｛２，２，２−トリフルオロ−１−［３−（トリフルオロメチル）フェニル］エチル｝−アクリルアミド１．５ｇ（８２％）が得られた。

tert-butyl {5-[(1E) -3-oxo-3-({2,2,2-trifluoro-1- [3- (trifluoromethyl) phenyl] ethyl} amino) prop-1-ene- 1-yl] -2,3-dihydro-1H-inden-1-yl} carbamate (2.2 g) was dissolved in 40 mL of dioxane, mixed with 10 mL of half-saturated hydrochloric acid, and stirred at room temperature overnight. The reaction mixture was mixed with water and extracted with ethyl acetate. The combined organic phases were dried over sodium sulfate, filtered and concentrated. This gave (2E) -3- (1-amino-2,3-dihydro-1H-inden-5-yl) -N- {2,2,2-trifluoro-1- [3- (trifluoromethyl ) Phenyl] ethyl} -acrylamide 1.5 g (82%) was obtained.

¹ H NMR (400 MHz, d ₆ -DMSO) δ = 2.02 (m, 1H), 2.49 (m, 1H), 2.92 (m, 1H), 3.09 (m, 1H), 4 .74 (m, 1H), 6.15 (p, 1H), 6.78 (d, 1H), 7.52-7.67 (m, 4H), 7.71 (t, 1H), 7. 82 (d, 1H), 7.97 (d, 1H), 8.06 (s, 1H), 8.45 (brs, 2H), 9.53 (d, 1H).

HPLC-MS: logP = 1.70; Mass (m / z): 412.2 ( M-NH 2) +.

Stage 6
(2E) -3- (1-acetamido-2,3-dihydro-1H-inden-5-yl) -N- {2,2,2-trifluoro-1- [3- (trifluoromethyl) phenyl] Ethyl} acrylamide (Compound No. Ie-1 in Table 5)

（２Ｅ）−３−（１−アミノ−２，３−ジヒドロ−１Ｈ−インデン−５−イル）−Ｎ−｛２，２，２−トリフルオロ−１−［３−（トリフルオロメチル）フェニル］エチル｝アクリルアミド１５０ｍｇをジクロロメタン５ｍＬに溶かし、Ｎ−メチルモルホリン７１ｍｇおよび無水酢酸３６ｍｇと混合し、室温で終夜撹拌した。反応混合物をロータリーエバポレータで濃縮して、（２Ｅ）−３−（１−アセトアミド−２，３−ジヒドロ−１Ｈ−インデン−５−イル）−Ｎ−｛２，２，２−トリフルオロ−１−［３−（トリフルオロメチル）フェニル］エチル｝アクリルアミド１６５ｍｇ（１００％）を得た。

(2E) -3- (1-Amino-2,3-dihydro-1H-inden-5-yl) -N- {2,2,2-trifluoro-1- [3- (trifluoromethyl) phenyl] 150 mg of ethyl} acrylamide was dissolved in 5 mL of dichloromethane, mixed with 71 mg of N-methylmorpholine and 36 mg of acetic anhydride, and stirred at room temperature overnight. The reaction mixture was concentrated on a rotary evaporator to give (2E) -3- (1-acetamido-2,3-dihydro-1H-inden-5-yl) -N- {2,2,2-trifluoro-1- 165 mg (100%) of [3- (trifluoromethyl) phenyl] ethyl} acrylamide was obtained.

¹ H NMR (400 MHz, d ₆ -DMSO): 1.78 (m, 1H), 1.87 (s, 3H), 2.40 (m, 1H), 2.82 (m, 1H), 2. 93 (m, 1H), 5.27 (q, 1H), 6.14 (m, 1H), 6.80 (d, 1H), 7.24 (d, 1H), 7.44 (d, 1H) ), 7.48 (s, 1H), 7.54 (d, 1H), 7.71 (t, 1H), 7.81 (d, 1H), 7.95 (d, 1H), 8.05 (S, 1H), 8.21 (d, 1H), 9.41 (d, 1H).

HPLC-MS: log P = 3.00; mass (m / z): 471.1 (M + H) ^<+> .

Synthesis Example 16 (Production of compounds of general formulas I-9 and VII-3 according to schemes 10d and 12d)
Stage 1
1- [4-Bromo-2- (trifluoromethyl) phenyl] methanamine

４−ブロモ−２−（トリフルオロメチル）ベンゾニトリル（Ｃｈｅｍ． Ｐｈａｒｍ． Ｂｕｌｌ． ２００５， ５３， ４， ４０２−４０９）１０．０ｇ（４０．０ｍｍｏｌ）のＴＨＦ（１１０ｍＬ）中溶液に、ＢＨ_３・Ｍｅ_２Ｓ溶液１８ｍＬ（１８０ｍｍｏｌ、１０Ｍ）を０℃でゆっくり加えた。混合物を０℃で３０分間撹拌し、昇温させて２５℃とし、３０分間撹拌した。次に、混合物を３０分間加熱還流した。冷却して室温とした後、反応混合物を１Ｍ ＮａＯＨ水溶液と混合し、酢酸エチルで抽出した（１５０ｍＬで３回）。合わせた有機相を合わせ、Ｎａ_２ＳＯ_４で脱水し、減圧下に濃縮した。得られた粗生成物を０℃でＨＣｌのエタノール中溶液と混合し、混合物を１時間撹拌した。混合物を減圧下に濃縮し、固体をジエチルエーテルで洗浄した。１−［４−ブロモ−２−（トリフルオロメチル）フェニル］メタンアミン塩酸塩９．０ｇ（７７％）を得た。

To a solution of 10.0 g (40.0 mmol) of 4-bromo-2- (trifluoromethyl) benzonitrile (Chem. Pharm. Bull. 2005, 53, 4, 402-409) in THF (110 mL) was added BH _3. 18 mL (180 mmol, 10M) of Me ₂ S solution was slowly added at 0 ° C. The mixture was stirred at 0 ° C. for 30 minutes, warmed to 25 ° C. and stirred for 30 minutes. The mixture was then heated to reflux for 30 minutes. After cooling to room temperature, the reaction mixture was mixed with 1M aqueous NaOH and extracted with ethyl acetate (3 x 150 mL). The combined organic phases were combined, dried over Na ₂ SO ₄ and concentrated under reduced pressure. The resulting crude product was mixed with a solution of HCl in ethanol at 0 ° C. and the mixture was stirred for 1 hour. The mixture was concentrated under reduced pressure and the solid was washed with diethyl ether. There was obtained 9.0 g (77%) of 1- [4-bromo-2- (trifluoromethyl) phenyl] methanamine hydrochloride.

HPLC-MS: log P = 0.92, mass (m / z): = 254.09 (M + H) ^<+> .

Stage 2
tert-Butyl [4-bromo-2- (trifluoromethyl) benzyl] carbamate

合成例１５段階１からのｔｅｒｔ−ブチル（５−ブロモ−２，３−ジヒドロ−１Ｈ−インデン−１−イル）カーバメートと同様にして、１−［４−ブロモ−２−（トリフルオロメチル）フェニル］メタンアミン塩酸塩をジ−ｔｅｒｔ−ブチルジカーボネートと反応させることで、ｔｅｒｔ−ブチル［４−ブロモ−２−（トリフルオロメチル）ベンジル］カーバメートを得た。

Synthesis Example 15 Similar to tert-butyl (5-bromo-2,3-dihydro-1H-inden-1-yl) carbamate from Step 1, 1- [4-bromo-2- (trifluoromethyl) phenyl Methaneamine hydrochloride was reacted with di-tert-butyl dicarbonate to obtain tert-butyl [4-bromo-2- (trifluoromethyl) benzyl] carbamate.

HPLC-MS: logP = 4.13, Mass _{(m / z): 297.9 (} M + -C 4 H 9) +.

¹ H NMR (400 MHz, CD ₃ CN): δ = 7.83 (m, 1H), 7.78 (d, 1H), 7.45 (d, 1H), 5.85 (s, 1H, br) 4.35 (d, 2H), 1.42 (s, 9H).

Stage 3
(2E) -3- [4-{[(tert-Butoxycarbonyl) amino] methyl} -3- (trifluoromethyl) phenyl] acrylic acid

合成例４段階３からの（２Ｅ）−３−［４−（シクロプロピルカルバモイル）−３−トリフルオロメチルフェニル］アクリル酸と同様にして、ｔｅｒｔ−ブチル［４−ブロモ−２−（トリフルオロメチル）ベンジル］カーバメートを（２Ｅ）−３−（４，４，５，５−テトラメチル−１，３，２−ジオキサボロラン−２−イル）アクリル酸エチルと反応させることで、（２Ｅ）−３−［４−｛［（ｔｅｒｔ−ブトキシカルボニル）アミノ］メチル｝−３−（トリフルオロメチル）フェニル］アクリル酸を得た。

Synthesis Example 4 In the same manner as (2E) -3- [4- (cyclopropylcarbamoyl) -3-trifluoromethylphenyl] acrylic acid from Step 3, tert-butyl [4-bromo-2- (trifluoromethyl) ) Benzyl] carbamate by reacting with (2E) -3- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) ethyl acrylate to give (2E) -3- [4-{[(tert-Butoxycarbonyl) amino] methyl} -3- (trifluoromethyl) phenyl] acrylic acid was obtained.

HPLC-MS: logP = 2.67, Mass _{(m / z): 290.1 (} M + -C 4 H 9) +.

¹ H NMR (400 MHz, CD ₃ CN): δ = 7.90 (s, 1H), 7.84 (d, 1H), 7.68 (d, 1H, J = 16 Hz), 7.57 (d, 1H), 6.55 (d, 1H, J = 16 Hz), 5.83 (s, 1H, br), 4.42 (d, 2H), 1.42 (s, 9H).

Stage 4
tert-butyl {4-[(1E) -3-oxo-3-({2,2,2-trifluoro-1- [3- (trifluoromethyl) phenyl] ethyl} amino) prop-1-ene- 1-yl] -2- (trifluoromethyl) benzyl} carbamate

（２Ｅ）−３−［４−｛［（ｔｅｒｔ−ブトキシカルボニル）アミノ］メチル｝−３−（トリフルオロメチル）フェニル］アクリル酸９８０ｍｇ（１当量、２．８４ｍｍｏｌ）のジクロロメタン（１０ｍＬ）中溶液に、６−クロロヒドロキシベンゾトリアゾール４８１ｍｇ（１当量、２．８４ｍｍｏｌ）および１−エチル−３−（３−ジメチルアミノプロピル）カルボジイミド塩酸塩（ＥＤＣ）７０７ｍｇ（１．３当量、３．７０ｍｍｏｌ）およびヒューニッヒ塩基７３３ｍｇ（２当量、５．６８ｍｍｏｌ、９８９μＬ）を加えた。反応混合物を室温で２０分間撹拌した。次に、ＣＨ_２Ｃｌ_２ １ｍＬ中の溶液としての２，２，２−トリフルオロ−１−［３−（トリフルオロメチル）フェニル］エタンアミン１．０４ｇ（１．５当量、４．２６ｍｍｏｌ）を加え、混合物を室温で１６時間撹拌した。反応混合物を減圧下に濃縮し、飽和Ｎａ_２ＣＯ_３溶液と酢酸エチルとの間で分配した。脱水および溶媒濃縮後に、ｔｅｒｔ−ブチル｛４−［（１Ｅ）−３−オキソ−３−（｛２，２，２−トリフルオロ−１−［３−（トリフルオロメチル）フェニル］エチル｝アミノ）プロプ−１−エン−１−イル］−２−（トリフルオロメチル）ベンジル｝カーバメート２．１０８ｇを油状物として得て、それをそれ以上精製せずに次の段階で変換した。

To a solution of (2E) -3- [4-{[(tert-butoxycarbonyl) amino] methyl} -3- (trifluoromethyl) phenyl] acrylic acid in 980 mg (1 eq, 2.84 mmol) in dichloromethane (10 mL) , 6-chlorohydroxybenzotriazole 481 mg (1 eq, 2.84 mmol) and 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (EDC) 707 mg (1.3 eq, 3.70 mmol) and Hunig's base 733 mg (2 eq, 5.68 mmol, 989 μL) was added. The reaction mixture was stirred at room temperature for 20 minutes. Next, 1.04 g (1.5 equivalents, 4.26 mmol) of 2,2,2-trifluoro-1- [3- (trifluoromethyl) phenyl] ethanamine as a solution in 1 mL of CH ₂ Cl ₂ was added. The mixture was stirred at room temperature for 16 hours. The reaction mixture was concentrated under reduced pressure and partitioned between saturated Na ₂ CO ₃ solution and ethyl acetate. After dehydration and solvent concentration, tert-butyl {4-[(1E) -3-oxo-3-({2,2,2-trifluoro-1- [3- (trifluoromethyl) phenyl] ethyl} amino) Prop-1-en-1-yl] -2- (trifluoromethyl) benzyl} carbamate 2.108 g was obtained as an oil which was converted in the next step without further purification.

HPLC-MS: log P = 4.40; mass (m / z): 571.40 (M + H) ^<+> .

Stage 5
(2E) -3- [4- (Aminomethyl) -3- (trifluoromethyl) phenyl] -N- {2,2,2-trifluoro-1- [3- (trifluoro-methyl) phenyl] ethyl } Acrylamide

Ｎ−Ｂｏｃシンナミド２ｇ（１当量、３．６ｍｍｏｌ）を４Ｍ ＨＣｌ／ジオキサン１３．７ｍＬ（１５当量、５５ｍｍｏｌ）に溶かし、室温で４時間撹拌した。次に、粗混合物を浴温＜３０℃で減圧下に濃縮した。得られた粗生成物（１．７ｇ）を、それ以上精製せずに次の段階で塩酸塩として用いた。

2 g of N-Boc cinnamide (1 equivalent, 3.6 mmol) was dissolved in 13.7 mL of 4M HCl / dioxane (15 equivalent, 55 mmol) and stirred at room temperature for 4 hours. The crude mixture was then concentrated under reduced pressure at a bath temperature <30 ° C. The resulting crude product (1.7 g) was used as the hydrochloride salt in the next step without further purification.

HPLC-MS: log P = 1.61, mass (m / z): 471.35 (M + H) ^<+> .

Stage 6
(2E) -3- {4-[(Isobutyrylamino) methyl] -3- (trifluoromethyl) phenyl} -N- {2,2,2-trifluoro-1- [3- (trifluoromethyl ) Phenyl] ethyl} acrylamide (Compound Ia-266 in Table 1)

イソブチリルクロライド３０ｍｇ（１．２当量、０．２８ｍｍｏｌ）をジクロロメタン１ｍＬに溶かした。これに、段階５からの（２Ｅ）−３−［４−（アミノメチル）−３−（トリフルオロメチル）フェニル］−Ｎ−｛２，２，２−トリフルオロ−１−［３−（トリフルオロメチル）フェニル］エチル｝アクリルアミドの塩酸塩１１３ｍｇ（１．０当量、０．２４ｍｍｏｌ）およびヒューニッヒ塩基９３ｍｇ（３当量）を加えた。混合物を室温で１６時間撹拌し、濃縮した。粗生成物をによって精製し分取ＨＰＬＣ（Ｐｈｅｎｏｍｅｎｅｘ Ｇｅｍｉｎｉ Ｃ１８ ５μｍ；１２５Ａ；Ａｑｕａ ５０×２１．２ｍｍ；勾配：０から１．５分：７８％水、２０％アセトニトリル、１．５から１０．０分：１８％水、８０％アセトニトリルまでの直線勾配、１０．０から１４．００分：１８％水、２０％アセトニトリル；調整剤：１０％ＮＨ_４ＨＣＯ_３を２ｍＬ／分で加えた）。これによって、（２Ｅ）−３−｛４−［（イソブチリルアミノ）メチル］−３−（トリフルオロメチル）フェニル｝−Ｎ−｛２，２，２−トリフルオロ−１−［３−（トリフルオロ−メチル）フェニル］エチル｝アクリルアミド５７ｍｇ（４４％）が得られる。

30 mg (1.2 eq, 0.28 mmol) of isobutyryl chloride was dissolved in 1 mL of dichloromethane. This was followed by (2E) -3- [4- (aminomethyl) -3- (trifluoromethyl) phenyl] -N- {2,2,2-trifluoro-1- [3- (tri 113 mg (1.0 eq, 0.24 mmol) of hydrochloride of fluoromethyl) phenyl] ethyl} acrylamide and 93 mg (3 eq) of Hunig's base were added. The mixture was stirred at room temperature for 16 hours and concentrated. The crude product was purified by preparative HPLC (Phenomenex Gemini C18 5 μm; 125A; Aqua 50 × 21.2 mm; gradient: 0 to 1.5 minutes: 78% water, 20% acetonitrile, 1.5 to 10.0 minutes. : 18% water, linear gradient to 80% acetonitrile, 10.0 to 14.00 min: 18% water, 20% acetonitrile; modifier: 10% NH ₄ HCO ₃ was added at 2 mL / min). This resulted in (2E) -3- {4-[(isobutyrylamino) methyl] -3- (trifluoromethyl) phenyl} -N- {2,2,2-trifluoro-1- [3- ( 57 mg (44%) of trifluoro-methyl) phenyl] ethyl} acrylamide are obtained.

HPLC-MS: log P = 3.78, mass (m / z): 541.2 (M + H) ^<+> .

¹ H NMR (400 MHz, d ₆ -DMSO): δ = 9.48 (d, 1H), 8.55 (t, 1H), 8.05 (s, 1H), 7.90 (m, 2H), 7.88 (d, 1H), 7.80 (d, 1H), 7.70 (t, 1H), 7.61 (d, 1H, J = 16 Hz), 7.50 (d, 1H), 6 .90 (d, 1H, J = 16 Hz), 6.15 (m, 1H), 4.43 (d, 2H), 2.50 (m, 1H), 1.06 (d, 6H).

Synthesis Example 17 (Production of compounds of general formulas I-6, II-1 and III-1 according to scheme 11a)
2,2,2-trifluoro-1- [3-fluoro-5- (trifluoromethyl) phenyl] ethanone
Stage 1

３−ブロモ−５−フルオロベンゾトリフルオリド５．００ｇ（２０．５７ｍｍｏｌ）を脱水エーテル６０ｍＬ中で撹拌し、保護ガス雰囲気（アルゴン）下に−７８℃で、ｔｅｒｔ−ブチルリチウム溶液［トリフルオロアシル化：Ｈ． Ｋ． Ｎａｉｒ， Ｄ． Ｍ． Ｑｕｉｎｎ Ｂｉｏｏｒｇａｎｉｃ ＆ Ｍｅｄｉｃｉｎａｌ Ｃｈｅｍｉｓｔｒｙ Ｌｅｔｔｅｒｓ ３（１２）， ２６１９−２２（１９９３）；Ｇ． Ｊ． Ｐｏｒｋ ｅｔ ａｌ．， Ｊ． Ｏｒｇ． Ｃｈｅｍ． ２２， ９９３（１９５７）も参照］１．３３ｍＬ（２０．７５ｍｍｏｌ）を滴下混合した。次に、反応混合物を−７８℃で４５分間撹拌し、注射器を用いて−７８℃で少量ずつ、トリフルオロ酢酸エチル３．７１ｇ（２６．１７ｍｍｏｌ）の脱水エーテル４０ｍＬ中溶液に少量ずつ滴下した。その後、反応混合物全体を、最初に−７８℃で１０分間撹拌し、次に室温で１時間撹拌した。後処理のため、反応混合物全体を水に加え、エーテルで抽出した。有機相を除去し、４０℃で真空乾燥した（化合物の揮発性が高いために、１ｋＰａ（１０ミリバール）以上）。これによって、２，２，２−トリフルオロ−１−［３−フルオロ−５−（トリフルオロメチル）フェニル］−エタノン４．０６ｇ（理論量の７５．９％）を得て、それを水和物として単離した。

Stir 5.00 g (20.57 mmol) of 3-bromo-5-fluorobenzotrifluoride in 60 mL of dehydrated ether and tert-butyllithium solution [trifluoroacylation] at −78 ° C. under a protective gas atmosphere (argon). : H. K. Nair, D.D. M.M. Quinn Bioorganic & Medicinal Chemistry Letters 3 (12), 2619-22 (1993); J. et al. Pork et al. , J. et al. Org. Chem. 22, 993 (1957)] 1.33 mL (20.75 mmol) was added dropwise. The reaction mixture was then stirred at −78 ° C. for 45 minutes and added dropwise, in small portions, at −78 ° C. using a syringe to a solution of 3.71 g (26.17 mmol) of ethyl trifluoroacetate in 40 mL of dehydrated ether. The entire reaction mixture was then first stirred at −78 ° C. for 10 minutes and then at room temperature for 1 hour. For workup, the entire reaction mixture was added to water and extracted with ether. The organic phase was removed and vacuum dried at 40 ° C. (1 kPa (10 mbar) or higher due to the high volatility of the compound). This gave 4.06 g (75.9% of theory) of 2,2,2-trifluoro-1- [3-fluoro-5- (trifluoromethyl) phenyl] -ethanone, which was hydrated Isolated as a product.

HPLC-MS: log P = 2.54, mass (m / z): 261.1 (M + H) ^<+> .

Stage 2
2,2,2-trifluoro-1- [3-fluoro-5- (trifluoromethyl) phenyl] ethanone oxime

段階１からの２，２，２−トリフルオロ−１−［３−フルオロ−５−（トリフルオロメチル）フェニル］エタノン水和物４．００ｇ（１５．３７ｍｍｏｌ）をピリジン３７．３ｍＬおよびエタノール２６．９ｍＬの混合物中で撹拌し、還流温度で約１８時間撹拌した。冷却後、反応混合物全体を水と混合し、減圧下に濃縮した。残った残留物を、シリカゲルを用いるカラムクロマトグラフィー（シリカゲル６０−Ｍｅｒｃｋ、粒径：０．０４から０．０６３ｍｍ；シクロヘキサン／アセトン勾配）によって精製して、２，２，２−トリフルオロ−１−［３−フルオロ−５−（トリフルオロメチル）フェニル］エタノンオキシム２．１８ｇ（理論量の５１．５％）をシン／アンチ異性体混合物として得た。

4.03 g (15.37 mmol) of 2,2,2-trifluoro-1- [3-fluoro-5- (trifluoromethyl) phenyl] ethanone hydrate from Step 1 was added to 37.3 mL of pyridine and 26. of ethanol. Stir in 9 mL of the mixture and stir at reflux for about 18 hours. After cooling, the entire reaction mixture was mixed with water and concentrated under reduced pressure. The remaining residue was purified by column chromatography using silica gel (silica gel 60-Merck, particle size: 0.04 to 0.063 mm; cyclohexane / acetone gradient) to give 2,2,2-trifluoro-1- 2.18 g (51.5% of theory) of [3-fluoro-5- (trifluoromethyl) phenyl] ethanone oxime was obtained as a syn / anti isomer mixture.

HPLC-MS: log P = 3.17; 3.21; mass (m / z): 275 (M) ^<+> .

Stage 3
α, 3-bis (trifluoromethyl) -5-fluorobenzenemethanamine

２，２，２−トリフルオロ−１−［３−フルオロ−５−（トリフルオロメチル）フェニル］エタノンオキシム２．１８ｇ（７．９２ｍｍｏｌ）をイソプロピルエーテル３５．４ｍＬ中で撹拌し、水素化リチウムアルミニウム３．５４ｇ（９３．３５ｍｍｏｌ）と少量ずつ混合した［アリールトリフルオロエチルアミン類の合成：ＤＥ２７２３４６４、１９７７）も参照］。その後、反応混合物を還流温度で約３時間撹拌した。後処理のため、反応混合物を冷却して０℃とし、飽和酒石酸溶液と注意深く混合して、過剰の水素化リチウムアルミニウムを破壊した。激しいガス発生が停止した後、混合物を２Ｎ水酸化ナトリウム溶液（アルカリ性）と混合し、有機相を除去した。水相をイソプロピルエーテルでさらに２回抽出した。その後、合わせた相を硫酸マグネシウムで脱水し、４０℃で減圧下に濃縮した（５ｋＰａ（５０ミリバール）以上）。これによって、α，３−ビス（トリフルオロメチル）−５−フルオロベンゼンメタンアミン１．５５ｇ（理論量の７１．７％）を得て、それをそれ以上精製せずにその後の反応に用いた。

2,2,2-trifluoro-1- [3-fluoro-5- (trifluoromethyl) phenyl] ethanone oxime 2.18 g (7.92 mmol) was stirred in 35.4 mL of isopropyl ether and lithium hydride It was mixed in small portions with 3.54 g (93.35 mmol) of aluminum [synthesis of aryltrifluoroethylamines: see also DE 2723464, 1977]. The reaction mixture was then stirred at reflux temperature for about 3 hours. For workup, the reaction mixture was cooled to 0 ° C. and carefully mixed with saturated tartaric acid solution to destroy excess lithium aluminum hydride. After vigorous gas evolution ceased, the mixture was mixed with 2N sodium hydroxide solution (alkaline) to remove the organic phase. The aqueous phase was extracted twice more with isopropyl ether. The combined phases were then dehydrated with magnesium sulfate and concentrated under reduced pressure at 40 ° C. (more than 5 kPa (50 mbar)). This gave 1.55 g (71.7% of theory) of α, 3-bis (trifluoromethyl) -5-fluorobenzenemethanamine, which was used in the subsequent reaction without further purification. .

HPLC-MS: log P = 2.51; mass (m / z): 262.1 (M + H) ^<+> .

¹ H NMR (CD ₃ CN, 400 MHz): δ = 4.61 (q, 1H), 7.46, 7.52 (2d, 1H aromatic), 7.64 (s, 1H aromatic).

Stage 4
N- [α, 3-bis (trifluoromethyl) -5-fluorobenzenemethane] -3-trifluoromethyl-4- (N-cyclopropylcarbamoyl) cinnamide (Compound No. Ia-229 in Table 1)

合成例４段階３からの（２Ｅ，Ｚ）−３−［４−（シクロプロピルカルバモイル）−３−（トリフルオロメチル）フェニル］アクリル酸９５．２５ｍｇ（０．３１ｍｍｏｌ）およびα，３−ビス（トリフルオロメチル）−５−フルオロベンゼンメタンアミンをジクロロメタン７ｍＬ中で撹拌し、１−［ビス（ジメチルアミノ）メチレン］−１Ｈ−１，２，３−トリアゾロ−［４，５−ｂ］ピリジニウム・ヘキサフルオロホスフェート３−オキサイド（ＨＡＴＵ）およびＮ，Ｎ−ジエチル−Ｎ−イソプロピルアミン（ヒューニッヒ塩基）と混合し、室温で３０時間撹拌した。その後、反応混合物全体を１Ｎ塩酸で洗浄し、有機相を除去し、硫酸ナトリウムで脱水した。減圧下に濃縮後、残った残留物を、シリカゲルを用いるカラムクロマトグラフィーによって２回精製した（シリカゲル６０−Ｍｅｒｃｋ、粒径：０．０４から０．０６３ｍｍ；シクロヘキサン／アセトン勾配）。これによって、Ｎ−［α，３−ビス（トリフルオロメチル）−５−フルオロベンゼンメタン］−３−トリフルオロメチル−４−（Ｎ−シクロプロピル−カルバモイル）シンナミド４２．３ｇ（理論量の２４．５％）を得た。

Synthesis Example 4 (2E, Z) -3- [4- (cyclopropylcarbamoyl) -3- (trifluoromethyl) phenyl] acrylic acid from step 3 95.25 mg (0.31 mmol) and α, 3-bis ( Trifluoromethyl) -5-fluorobenzenemethanamine is stirred in 7 mL of dichloromethane and 1- [bis (dimethylamino) methylene] -1H-1,2,3-triazolo- [4,5-b] pyridinium hexa It was mixed with fluorophosphate 3-oxide (HATU) and N, N-diethyl-N-isopropylamine (Hunig base) and stirred at room temperature for 30 hours. Thereafter, the entire reaction mixture was washed with 1N hydrochloric acid, the organic phase was removed, and dehydrated with sodium sulfate. After concentration under reduced pressure, the remaining residue was purified twice by column chromatography using silica gel (silica gel 60-Merck, particle size: 0.04 to 0.063 mm; cyclohexane / acetone gradient). This gives 42.3 g of N- [α, 3-bis (trifluoromethyl) -5-fluorobenzenemethane] -3-trifluoromethyl-4- (N-cyclopropyl-carbamoyl) cinnamide (24. 5%).

HPLC-MS: log P = 3.59; mass (m / z) 543.2 (M) ^<+> .

Synthesis Example 18 (Production of compound of general formula (VII-3) according to schemes 10d and 12b)
Stage 1
1- (4-Bromo-2-fluorophenyl) ethanamine

４−ブロモ−２−フルオロベンゾニトリル１２ｇ（６０ｍＭ）のＴＨＦ（１２０ｍＬ）中溶液に、２Ｍメチルマグネシウムブロマイド／ジエチルエーテル溶液７５ｍＬ（１５０ｍＭ）を０℃で加えた。反応混合物を０℃で６時間撹拌した。次に、メタノール２００ｍＬを反応混合物に徐々に加えた。次に、水素化ホウ素ナトリウム５．７ｇ（１５０ｍＭ）を少量ずつ加え、混合物を室温で１６時間撹拌した。その後、反応混合物を減圧下に濃縮し、水２００ｍＬを加えた。２Ｍ ＨＣｌでｐＨ＝約１にｐＨを調節し、その水溶液をクロロホルムで抽出した。次に、２Ｍ ＮａＯＨでｐＨをｐＨ＝約９に調節し、クロロホルムで抽出した（１００ｍＬで２回）。合わせたクロロホルム抽出液を脱水し、溶媒を減圧下に除去した。１−（４−ブロモ−２−フルオロフェニル）エタンアミン７．３ｇ（４４％）を黄色油状物として得た。

To a solution of 12 g (60 mM) 4-bromo-2-fluorobenzonitrile in THF (120 mL) was added 75 mL (150 mM) 2M methylmagnesium bromide / diethyl ether solution at 0 ° C. The reaction mixture was stirred at 0 ° C. for 6 hours. Next, 200 mL of methanol was slowly added to the reaction mixture. Next, 5.7 g (150 mM) of sodium borohydride was added in small portions and the mixture was stirred at room temperature for 16 hours. The reaction mixture was then concentrated under reduced pressure and 200 mL of water was added. The pH was adjusted to about 1 with 2M HCl and the aqueous solution was extracted with chloroform. The pH was then adjusted to pH = about 9 with 2M NaOH and extracted with chloroform (2 × 100 mL). The combined chloroform extracts were dehydrated and the solvent was removed under reduced pressure. 7.3 g (44%) of 1- (4-bromo-2-fluorophenyl) ethanamine was obtained as a yellow oil.

¹ H NMR (400 MHz, CDCl ₃ ): δ = 1.39 (d, 3H), 1.61 (s, 2H, br), 4.34 (m, 1H), 7.18 (m, 3H).

Stage 2
N- [1- (4-Bromo-2-fluorophenyl) ethyl] propanamide

段階１からの１−（４−ブロモ−２−フルオロフェニル）エタンアミン６１ｍｇ（１当量、０．２４ｍｍｏｌ）をジクロロメタン４ｍＬに溶かし、プロパノイルクロライド２４ｍｇ（１．１当量、２３μＬ、０．２６４ｍｍｏｌ）およびヒューニッヒ塩基７０ｍｇ（２．２当量、９０μＬ）を加えた。混合物を室温で５時間撹拌し、濃縮した。粗生成物を酢酸エチルに溶かし、１Ｍ ＨＣｌで１回、飽和炭酸ナトリウム溶液で１回、次に水で洗浄し、硫酸マグネシウムで脱水した。減圧下に濃縮後、得られた粗生成物をシリカゲルでのクロマトグラフィー（溶離液：シクロヘキサン／酢酸エチル）によって精製した。Ｎ−［１−（４−ブロモ−２−フルオロフェニル）エチル］プロパンアミド５０ｍｇ（６７％）を得た。

61 mg (1 eq, 0.24 mmol) of 1- (4-bromo-2-fluorophenyl) ethanamine from Step 1 is dissolved in 4 mL of dichloromethane, 24 mg of propanoyl chloride (1.1 eq, 23 μL, 0.264 mmol) and Hunig 70 mg (2.2 eq, 90 μL) of base was added. The mixture was stirred at room temperature for 5 hours and concentrated. The crude product was dissolved in ethyl acetate, washed once with 1M HCl, once with saturated sodium carbonate solution, then with water and dried over magnesium sulfate. After concentration under reduced pressure, the resulting crude product was purified by chromatography on silica gel (eluent: cyclohexane / ethyl acetate). N- [1- (4-Bromo-2-fluorophenyl) ethyl] propanamide 50 mg (67%) was obtained.

HPLC-MS: log P = 2.19, mass (m / z): 276.1 (M + H) ^<+> .

¹ H NMR (400 MHz, DMSO-d ₆ ): δ = 8.25 (d, 1H, br), 7.46 (dd, 1H), 7.39 (dd, 1H), 7.30 (t, 1H) ), 5.05 (m, 1H), 2.10 (q, 2H), 1.31 (d, 3H), 0.97 (t, 3H).

Synthesis Example 19 (Production of compound of general formula (VII-4) according to schemes 10e and 12a)
N- [4-Bromo-2- (trifluoromethyl) benzyl] pyridin-2-amine

ｔｅｒｔ−ブチルピリジン−２−イルカーバメート０．６１ｇ（３．２ｍｍｏｌ）の脱水ＤＭＦ（１０ｍＬ）中溶液に、ＮａＨ０．１８ｇ（６０％、４．４ｍｍｏｌ）を０℃で少量ずつ加え、混合物を０℃で３０分間撹拌した。次に、４−ブロモ−１−（ブロモメチル）−２−（トリフルオロメチル）ベンゼン（ＷＯ２００６／１８７２５）１．１ｇ（３．５ｍｍｏｌ）を、脱水ＤＭＦ（５．０ｍＬ）中の溶液として０℃で加えた。反応混合物をゆっくり昇温させて室温とし、２時間撹拌した。その後、それを水と混合し、酢酸エチルで抽出した。有機相を脱水し、減圧下に濃縮した。得られた粗生成物をシリカゲルクロマトグラフィー（ｎ−ヘキサン／酢酸エチル３０：１から１０：１）によって精製して、Ｎ−Ｂｏｃ−保護アミン１．１ｇ（７７％）を得た。

To a solution of 0.61 g (3.2 mmol) of tert-butylpyridin-2-ylcarbamate in dehydrated DMF (10 mL) was added 0.18 g (60%, 4.4 mmol) of NaH in portions at 0 ° C. For 30 minutes. Next, 1.1 g (3.5 mmol) of 4-bromo-1- (bromomethyl) -2- (trifluoromethyl) benzene (WO 2006/18725) as a solution in dehydrated DMF (5.0 mL) at 0 ° C. added. The reaction mixture was slowly warmed to room temperature and stirred for 2 hours. It was then mixed with water and extracted with ethyl acetate. The organic phase was dried and concentrated under reduced pressure. The resulting crude product was purified by silica gel chromatography (n-hexane / ethyl acetate 30: 1 to 10: 1) to give 1.1 g (77%) of N-Boc-protected amine.

This was dissolved in 20 mL of HCl-saturated ethyl acetate and stirred overnight at room temperature. The solution was then neutralized with aqueous K ₂ CO ₃ and extracted with ethyl acetate. After dehydration and solvent removal, 0.8 g (75%) of N- [4-bromo-2- (trifluoromethyl) benzyl] pyridin-2-amine was obtained as a solid.

HPLC-MS: log P = 1.57, mass (m / z): 333.0 (M + H) ^<+> .

¹ H NMR (400 MHz, CD ₃ CN): δ = 7.96 (dd, 1H), 7.78 (m, 1H), 7.68 (m, 1H), 7.50 (d, 1H), 7 .43-7.39 (m, 1H), 6.58-6.56 (m, 1H), 6.50 (d, 1H), 5.68 (s, 1H, br), 4.68 (d) 2H).

  The compounds of the invention of the general formulas (Ia), (Ib), (Ic), (Id), (Ie), (If) and (Ig) described in Tables 1 to 7 are also the synthetic examples described above. Preferred compounds of the invention obtained according to or in the same manner.

Table 1

式中、Ｒ^２、Ｒ^４およびＲ^５はそれぞれＨであり、ＸはＣＦ_３であり、（Ｒ^１）_ｎ、Ｒ^３、（Ｒ^６）_ｍ、ＡおよびＹはそれぞれ表１に定義の通りである。数字２から６は芳香環上の位置を表す。

In the formula, R ² , R ⁴ and R ⁵ are each H, X is CF ₃ , (R ¹ ) _n , R ³ , (R ⁶ ) _m , A and Y are as defined in Table 1. It is. Numbers 2 to 6 represent positions on the aromatic ring.

表２

Table 2

式中、Ｒ^２、Ｒ^３、Ｒ^４およびＲ^５はそれぞれＨであり、ＸはＣＦ_３であり、Ｑ^１、Ｑ^２、Ｑ^３、（Ｒ^１）_ｎ、（Ｒ^６）_ｍ、ＡおよびＹはそれぞれ表２で定義の通りである。数字２から６は芳香環上の位置を表す。

Wherein R ² , R ³ , R ⁴ and R ⁵ are each H, X is CF ₃ , Q ¹ , Q ² , Q ³ , (R ¹ ) _n , (R ⁶ ) _m , A and Y is as defined in Table 2. Numbers 2 to 6 represent positions on the aromatic ring.

Table 3

Ｒ^２およびＲ^５はそれぞれＨであり、ＸはＣＦ_３であり、（Ｒ^１）_ｎ、Ｒ^３、Ｖ、（Ｒ^６）_ｍ、ＡおよびＹはそれぞれ表３で定義の通りである。数字２から６または２から５は、芳香環上の位置を表す。

R ² and R ⁵ are each H, X is CF ₃ , (R ¹ ) _n , R ³ , V, (R ⁶ ) _m , A and Y are as defined in Table 3. The numbers 2 to 6 or 2 to 5 represent positions on the aromatic ring.

表４

Table 4

式中、Ｒ^２、Ｒ^３、Ｒ^４はそれぞれＨであり、Ｘ、（Ｒ^１）_ｎ、Ｒ^５、（Ｒ^６）_ｍ、ＡおよびＹはそれぞれ表４で定義の通りである。数字２から６は芳香環上の位置を表す。

In the formula, R ² , R ³ and R ⁴ are each H, and X, (R ¹ ) _n , R ⁵ , (R ⁶ ) _m , A and Y are as defined in Table 4. Numbers 2 to 6 represent positions on the aromatic ring.

Table 5

式中、Ｒ^２、Ｒ^３、Ｒ^４およびＲ^５はそれぞれＨであり、ＸはＣＦ_３であり、（Ｒ^１）_ｎ、Ｒ^１３およびＹはそれぞれ表５で定義の通りである。数字２から６は芳香環上の位置を表す。

In the formula, R ² , R ³ , R ⁴ and R ⁵ are each H, X is CF ₃ , and (R ¹ ) _n , R ¹³ and Y are as defined in Table 5, respectively. Numbers 2 to 6 represent positions on the aromatic ring.

Table 6

式中、Ｒ^２、Ｒ^３、Ｒ^４およびＲ^５はそれぞれＨであり、ＸはＣＦ_３であり、Ｑ^４、Ｑ^５、（Ｒ^１）_ｎ、（Ｒ^６）_ｍ、ＡおよびＹはそれぞれ表６で定義の通りである。数字２から６は芳香環上の位置を表す。

Wherein R ² , R ³ , R ⁴ and R ⁵ are each H, X is CF ₃ , Q ⁴ , Q ⁵ , (R ¹ ) _n , (R ⁶ ) _m , A and Y are each As defined in Table 6. Numbers 2 to 6 represent positions on the aromatic ring.

Table 7

式中、Ｒ^２、Ｒ^３、Ｒ^４およびＲ^５はそれぞれＨであり、ＸはＣＦ_３であり、（Ｒ^１）_ｎ、（Ｒ^６）_ｍ、ＡおよびＹはそれぞれ表７で定義の通りである。数字２から６は芳香環上の位置を表す。

Wherein R ² , R ³ , R ⁴ and R ⁵ are each H, X is CF ₃ , (R ¹ ) _n , (R ⁶ ) _m , A and Y are as defined in Table 7 It is. Numbers 2 to 6 represent positions on the aromatic ring.

ａ）Ｍ＋は、ｐＨ２．７の酸性範囲、溶離液としてのアセトニトリル（０．１％ギ酸を含む）および水；１０％アセトニトリルから９５％アセトニトリルの直線勾配；装置：Ａｇｉｌｅｎｔ １１００ＬＣ−システム、Ａｇｉｌｅｎｔ ＭＳＤシステム、ＨＴＳＰＡＬでのＬＣ−ＭＳによって測定される。

a) M + is an acidic range of pH 2.7, acetonitrile (with 0.1% formic acid) and water as eluent; linear gradient from 10% acetonitrile to 95% acetonitrile; apparatus: Agilent 1100LC-system, Agilent MSD system , Measured by LC-MS on HTSPAL.

  The logP values reported in the above table and in the production examples are EEC Directive 79/831 Annex V. According to A8, determined by HPLC (high performance liquid chromatography) on a reverse phase column (C18). Temperature 43 ° C. Calibration is performed using unbranched alkane-2-ones (3 to 16 carbon atoms) with known log P values.

b) ¹ H NMR data is measured by Bruker Avance 400 using tetramethylsilane as a reference (0.0) and solvents CD ₃ CN, CDCl ₃ , [D ₆ ] -DMSO. Signal splitting is s = single line, brs = wide single line, d = double line, t = triple line, q = quadruple line, quint = quintet line, m = multiple line, dd = double double line Characterized by lines.

Application Examples The following examples show the insecticidal and acaricidal activity of the compounds of the invention. The compounds of the invention referred to relate to the compounds listed in Tables 1 to 7, with the corresponding reference symbols (eg: Ia-1).

Example 1
Boophilus microplus test (BOOPMI injection)
Solvent: Dimethylsulfoxide In order to prepare the active ingredient preparation, 10 mg of the active ingredient is mixed with 0.5 mL of the solvent, and the resulting concentrated solution is diluted with water to obtain a desired concentration. The active ingredient solution was injected into the abdomen (Boophilus microplus) and the animal was transferred to a petri dish and stored in a temperature / humidity controlled room. Efficacy was evaluated by the number of eggs laid in the fertilized egg.

  After 7 days, determine the efficacy in%. 100% means that there were no ticks that laid fertilized eggs.

  In this test, the following compounds of the invention show the indicated effects.

100% potency at doses of 20 μg / animal Ia-5, Ia-8, Ia-22, Ia-23, Ia-24, Ia-29, Ia-30, Ia-31, Ia-32, Ia-40, Ia-41, Ia-42, Ia-43, Ia-44, Ia-45, Ia-46, Ia-58, Ia-60, Ia-73, Ia-76, Ia-77, Ia-80.

Example 2
Cat flea (Ctenocephalides felis); Oral (CTECFE)
Solvent: 1 part by weight of dimethyl sulfoxide To prepare an active ingredient formulation, 10 mg of active ingredient is mixed with 0.5 mL of dimethyl sulfoxide. Part of the resulting concentrated solution was diluted with bovine blood to which citrate had been added to obtain the desired concentration.

  Twenty fasting fleas (Ctenocephalides felis) are placed in a chamber whose top and bottom are closed with gauze. A metallic cylinder whose lower end is closed with parafilm is placed on the chamber. The cylinder contains a blood-active ingredient preparation, which can be taken up by fleas through a parafilm membrane.

  Two days later, the insecticidal rate (%) is obtained. Here, 100% means that all cat fleas have been killed, and 0% means that none of the cat fleas have been killed.

  In this test, the following compounds of the present invention show the indicated effects.

95% potency Ia-73 at an application rate of 20 ppm ; Ia-31.

  In this test, the following compounds of the present invention show the indicated effects.

98% potency Ia-45 at an application rate of 20 ppm ; Ia-58.

  In this test, the following compounds of the present invention show the indicated effects.

100% potency at 20 ppm application rate Ia-22, Ia-23, Ia-24, Ia-30, Ia-32, Ia-40, Ia-41, Ia-42, Ia-43, Ia-60, Ia-80 .

Example 3
Sheep flies (Lucilia cuprina) test (LUCICU)
Solvent: dimethyl sulfoxide In order to prepare the active ingredient preparation, 10 mg of the active ingredient is mixed with 0.5 mL of dimethyl sulfoxide, and the concentrated solution is diluted with water to obtain a desired concentration. Larvae of the sheep fly (Lucilia cuprina) are inhabited in a container containing horse meat treated with the active ingredient preparation of the desired concentration.

  Two days later, the insecticidal rate (%) is obtained. 100% means that all larvae have been killed; 0% means that no larvae have been killed.

  In this test, the following compounds of the present invention show the indicated effects.

80% potency Ia-24 at 20 ppm application rate .

  In this test, the following compounds of the present invention show the indicated effects.

90% potency Ia-22, Ia-40, Ia-41, Ia-60 at an application rate of 20 ppm .

  In this test, the following compounds of the present invention show the indicated effects.

100% potency Ia-23, Ia-30, Ia-42, Ia-43, Ia-45 at an application rate of 20 ppm .

Example 4
Musca domestica test (MUSCDO)
Solvent: dimethyl sulfoxide In order to prepare the active ingredient preparation, 10 mg of the active ingredient is mixed with 0.5 mL of dimethyl sulfoxide, and the concentrated solution is diluted with water to obtain a desired concentration. Houseflies (Musca domestica) are inhabited in a container containing a sponge treated with a desired concentration of active ingredient preparation.

  Two days later, the insecticidal rate (%) is obtained. 100% means that all the houseflies have died, 0% means that none of the houseflies have died.

  In this test, the following compounds of the present invention show the indicated effects.

85% potency Ia-30 at 20 ppm application rate .

Example 5
Aphid test (MYZUPE spray treatment)
Solvent: 78 parts by weight of acetone 1.5 parts by weight of dimethylformamide Emulsifier: 0.5 parts by weight of alkylaryl polyglycol ether.

  In order to prepare the active ingredient preparation, 1 part by weight of the active ingredient is mixed with a specified amount of a solvent and an emulsifier, and the concentrate is diluted with water containing the emulsifier to obtain a desired concentration. The active ingredient formulation of the desired concentration is sprayed onto discoid slices of Chinese cabbage (Brassica pekinensis) with all stages of the peach aphid (Myzus persicae).

  After 6 days, determine the efficacy in%. 100% means that all aphids have died, 0% means that no aphids have died.

  In this test, the following compounds of the present invention show the indicated effects.

80% potency Ia-75 at an application rate of 20 g / ha .

  In this test, the following compounds of the present invention show the indicated effects.

90% potency Ia-115 at an application rate of 20 g / ha .

  In this test, the following compounds of the present invention show the indicated effects.

100% potency Ia-41 at an application rate of 20 g / ha ; Ia-112.

Example 6
Spodoptera frugiperda test (SPODFR spray treatment)
Solvent: 78.0 parts by weight of acetone 1.5 parts by weight of dimethylformamide Emulsifier: 0.5 parts by weight of alkylaryl polyglycol ether In order to prepare the active ingredient formulation, Mix with emulsifier and dilute the resulting concentrate with water containing emulsifier to the desired concentration. The active ingredient preparation of a desired concentration is sprayed on a disk-like slice of corn (Zea mays) leaves, and after drying, larvae of armyworm (Spodoptera frugiperda) are infested.

  After 7 days, determine the efficacy (%). 100% means that all larvae are dead, and 0% means that none of the larvae are dead.

  In this test, the following compounds of the present invention show the indicated effects.

83% potency Ia-23; Ia-72; Ia-82 at an application rate of 20 g / ha .

  In this test, the following compounds of the present invention show the indicated effects.

100% potency Ia-54 at an application rate of 20 g / ha .

Example 7
Phaedon test (PHAECO spray treatment)
Solvent: 78.0 parts by weight of acetone 1.5 parts by weight of dimethylformamide Emulsifier: 0.5 parts by weight of alkylaryl polyglycol ether.

  In order to produce an active ingredient preparation, 1 part by weight of the active ingredient is mixed with a specified amount of a solvent and an emulsifier, and the concentrate is diluted with water containing the emulsifier to obtain a desired concentration. The active ingredient preparation of a desired concentration is sprayed on a disc-shaped slice of Chinese cabbage leaf (Brassica pekinensis), and after drying, larvae of mustard beetle (Phaedon cochleariae) are inhabited.

  After 7 days, determine the efficacy in%. 100% means that all beetle larvae have died, 0% means that no beetle larvae have died.

  In this test, the following compounds of the present invention show the indicated effects.

100% potency at application rate 20 g / ha Ia-21, Ia-22, Ia-23, Ia-37, Ia-41, Ia-43, Ia-47, Ia-48, Ia-51, Ia-54, Ia -56, Ia-57, Ia-58, Ia-59, Ia-60, Ia-61, Ia-62, Ia-63, Ia-64, Ia-65, Ia-66, Ia-67, Ia-68 Ia-69, Ia-70, Ia-71, Ia-72, Ia-73, Ia-74, Ia-75, Ia-76, Ia-78, Ia-79, Ia-80, Ia-82, Ia -83, Ia-84, Ia-86, Ia-87, Ia-88, Ia-89, Ia-90, Ia-91, Ia-92, Ia-93, Ia-94, Ia-95, Ia-96 Ia-97, Ia-98, Ia-99, Ia-100, Ia-1 1, Ia-102, Ia-103, Ia-104, Ia-105, Ia-106, Ia-107, Ia-108, Ia-109, Ia-110, Ia-111, Ia-112, Ia-113, Ia-114, Ia-115, Ic-18, Ic-18, Ic-20, Ic-21, Ic-22, Ic-23, Ic-24.

Example 8
Tetranychus test; OP resistance (TETRUR spray treatment)
Solvent: 78.0 parts by weight of acetone 1.5 parts by weight of dimethylformamide Emulsifier: 0.5 parts by weight of alkylaryl polyglycol ether In order to prepare the active ingredient formulation, Mix with emulsifier and dilute the resulting concentrate with water containing emulsifier to the desired concentration.

  The active ingredient formulation of the desired concentration is sprayed onto the disk-shaped slices of common bean (Phaseolus vulgaris) in which red spider mite (Tetranychus urticae) is developing at all stages of growth.

  After 6 days, determine the efficacy (%). 100% means that all red mites have died, 0% means that none of the mites have died.

  In this test, the following compounds of the present invention show the indicated effects.

80% efficacy Ia-63, Ia-77, Ia-90, Ia-92, Ia-94, Ia-95, Ia-96, Ia-99, Ia-100, Ic-18 at an application rate of 20 g / ha .
In the test, the following compounds of the present invention show the indicated effects.

90% potency at application rate 20 g / ha Ia-23, Ia-47, Ia-48, Ia-49, Ia-51, Ia-57, Ia-58, Ia-60, Ia-65, Ia-66, Ia -74, Ia-78, Ia-79, Ia-93, Ia-115.

  In this test, the following compounds of the present invention show the indicated effects.

100% potency at application rates of 20 g / ha Ia-23, Ia-36, Ia-41, Ia-50, Ia-52, Ia-54, Ia-55, Ia-56, Ia-59, Ia-61, Ia -62, Ia-68, Ia-69, Ia-70, Ia-73, Ia-75, Ia-112, Ia-113, Ia-114.

Example 9
Amblyomma hebaraeum test (AMBYHE)
Solvent: dimethyl sulfoxide To prepare a suitable active ingredient formulation, 10 mg of active ingredient is mixed with 0.5 mL of dimethyl sulfoxide, and the resulting concentrate is diluted with water to the desired concentration. Ticks (Amblyommahebaraeum) larvae are placed in a perforated plastic cup and soaked for 1 minute at the desired concentration. The ticks are transferred onto filter paper in a petri dish and stored in a temperature / humidity controlled cabinet.

  After 42 days, the insecticidal rate (%) is determined. Here, 100% means that all ticks have died and 0% means that no ticks have died.

  In this test, the following compounds from the preparation examples show 100% efficacy at an application rate of 100 ppm: Ia-161, Ia-162.

Example 10
Boophilus microplus test (immersion)
Test animals: SP-resistant adult percussion adult saturated ticks Solvent: dimethyl sulfoxide.

  10 mg of active ingredient is dissolved in 0.5 mL of dimethyl sulfoxide. In order to prepare suitable formulations, the active ingredient solution is diluted with water to the desired concentration in each case.

  This active ingredient formulation is put into a test tube using a pipette. Transfer 8 to 10 ticks into another test tube with holes. The test tube is immersed in the active ingredient formulation to completely wet all ticks. After draining the liquid, the mites are transferred onto a filter disc in a plastic dish and stored in a temperature / humidity controlled room. Seven days later, the efficacy is evaluated by the number of eggs laid by the fertilized egg. Eggs whose appearance of fertility is not apparent are stored in glass tubes in a temperature / humidity controlled cabinet until the larvae hatch. 100% potency means that there were no ticks that laid fertilized eggs.

  In this test, for example, the following compounds from the preparation examples show 100% efficacy at an application rate of 100 ppm: Ia-112, Ia-162.

  In this test, for example, the following compound from the preparation example shows 98% efficacy at an application rate of 100 ppm: Ia-161.

  In this test, for example, the following compound from the preparation example shows 90% efficacy at an application rate of 100 ppm: Ia-155.

  In this test, for example, the following compound from the preparation example shows 85% efficacy at an application rate of 100 ppm: Ia-114.

Example 11
Boophilus microplus test (BOOPMI injection)
Solvent: dimethyl sulfoxide In order to prepare a suitable active ingredient formulation, 10 mg of active ingredient is mixed with 0.5 mL of solvent, and the resulting concentrated solution is diluted with a solvent to a desired concentration. The active ingredient solution is injected into the abdomen (Boophilus microplus) and the animal is transferred to a petri dish and stored in a temperature / humidity controlled room. Efficacy was evaluated by the number of eggs laid in the fertilized egg.

  After 7 days, determine the efficacy in%. 100% means that there were no ticks that laid fertilized eggs.

  In this test, for example, the following compounds from the preparation examples show 100% efficacy at an application rate of 20 μg / animal: Ia-5, Ia-8, Ia-18, Ia-19, Ia-21, Ia- 22, Ia-23, Ia-24, Ia-29, Ia-30, Ia-31, Ia-32, Ia-36, Ia-40, Ia-41, Ia-42, Ia-43, Ia-44 Ia-45, Ia-46, Ia-54, Ia-57, Ia-58, Ia-60, Ia-73, Ia-75, Ia-76, Ia-77, Ia-80, Ia-82, Ia- 94, Ia-112, Ia-114, Ia-121, Ia-122, Ia-123, Ia-124, Ia-125, Ia-126, Ia-127, Ia-128, Ia-129, Ia-130, Ia-132, Ia-134, Ia-13 Ia-136, Ia-138, Ia-139, Ia-140, Ia-141, Ia-142, Ia-143, Ia-144, Ia-145, Ia-146, Ia-147, Ia-148, Ia -149, Ia-150, Ia-151, Ia-152, Ia-153, Ia-154, Ia-155, Ia-156, Ia-157, Ia-158, Ia-159, Ia-161, Ia-162 Ia-163, Ia-164, Ia-237, Ic-18, Ic-24, Ic-25.

Example 12
Cat flea (Ctenocephalides felis); Oral (CTECFE)
Solvent: 1 part by weight of dimethyl sulfoxide To prepare a suitable active ingredient formulation, 10 mg of the active ingredient is mixed with 0.5 mL of dimethyl sulfoxide. Part of the resulting concentrate is diluted with bovine blood to which citrate has been added to obtain the desired concentration.

  About 20 fasting flea (Ctenocephalis felis) adults are placed in a chamber whose top and bottom are closed with gauze. A metallic cylinder whose lower end is closed with parafilm is placed on the chamber. The cylinder contains a blood-active ingredient preparation, which can be taken up by fleas through a parafilm membrane. Two days later, the insecticidal rate (%) is obtained. Here, 100% means that all cat fleas have been killed, and 0% means that none of the cat fleas have been killed.

  In this test, for example, the following compounds from the preparation examples show 100% efficacy at an application rate of 100 ppm.

本試験では、例えば、製造例からの下記の化合物が、施用量１００ｐｐｍで９８％の効力を示す：Ｉａ−１８。

In this test, for example, the following compound from the preparation example shows 98% efficacy at an application rate of 100 ppm: Ia-18.

  In this test, for example, the following compound from the preparation example shows 95% efficacy at an application rate of 100 ppm: Ia-54.

  In this test, for example, the following compound from the preparation example shows 90% potency at an application rate of 100 ppm: Ia-146.

  In this test, for example, the following compounds from the preparation examples show an efficacy of 80% at an application rate of 100 ppm: Ia-5, Ia-76.

Example 13
Sheep flies (Lucilia cuprina) test (LUCICU)
Solvent: dimethyl sulfoxide To prepare a suitable active ingredient formulation, 10 mg of active ingredient is mixed with 0.5 mL of dimethyl sulfoxide and the concentrate is diluted with water to the desired concentration. Approximately 20 larvae of the sheep flies (Lucilia cuprina) are inhabited in a container containing horse meat treated with the active ingredient preparation of the desired concentration.

  Two days later, the insecticidal rate (%) is obtained. 100% means that all larvae have been killed; 0% means that no larvae have been killed.

  In this test, for example, the following compounds from the preparation examples show 100% efficacy at an application rate of 100 ppm.

本試験では、例えば、製造例からの下記の化合物が、施用量１００ｐｐｍで９５％の効力を示す：Ｉａ−９４。

In this test, for example, the following compound from the preparation example shows 95% efficacy at an application rate of 100 ppm: Ia-94.

In this test, for example, the following compounds from the preparation examples show 90% efficacy at an application rate of 100 ppm: Ia-31, Ia-128, Ia-134, Ia-142,
Ia-152.

  In this test, for example, the following compounds from the preparation examples show an efficacy of 80% at an application rate of 100 ppm: Ia-29, Ia-73, Ia-80, Ia-139, Ia-147.

Example 14
Musca domestica test (MUSCDO)
Solvent: dimethyl sulfoxide To prepare a suitable active ingredient formulation, 10 mg of active ingredient is mixed with 0.5 mL of dimethyl sulfoxide and the concentrate is diluted with water to the desired concentration. Houseflies (Musca domestica) are inhabited in a container containing a sponge treated with a desired concentration of active ingredient preparation.

  Two days later, the insecticidal rate (%) is obtained. 100% means that all the houseflies have died, 0% means that none of the houseflies have died.

  In this test, for example, the following compounds from the preparation examples show 100% efficacy at an application rate of 100 ppm: Ia-19, Ia-23, Ia-30, Ia-45, Ia-57, Ia-140, Ia-141, Ia-149, Ia-158, Ia-163, Ic-25.

  In this test, for example, the following compound from the preparation example shows 95% efficacy at an application rate of 100 ppm: Ia-60.

In this test, for example, the following compounds from the preparation examples show 90% potency at an application rate of 100 ppm: Ia-18, Ia-122, Ia-142, Ia-148,
Ia-156.

  In this test, for example, the following compound from the preparation example shows 85% efficacy at an application rate of 100 ppm: Ia-40.

  In this test, for example, the following compounds from the preparation examples show 80% potency at an application rate of 100 ppm: Ia-151, Ia-161.

Example 15
Spodoptera frugiperda test (SPODFR spray treatment)
Solvent: 78.0 parts by weight of acetone 1.5 parts by weight of dimethylformamide Emulsifier: 0.5 parts by weight of alkylaryl polyglycol ether In order to prepare a suitable active ingredient formulation, Mixing with solvent and emulsifier, the resulting concentrated solution was diluted with emulsifier-containing water to obtain the desired concentration. The active ingredient preparation of a desired concentration is sprayed on a disk-like slice of corn (Zea mays) leaves, and after drying, larvae of armyworm (Spodoptera frugiperda) are infested.

  After 7 days, determine the efficacy (%). 100% means that all larvae are dead, and 0% means that none of the larvae are dead.

  In this test, for example, the following compounds from the preparation examples show 100% efficacy at an application rate of 500 g / ha.

本試験では、例えば、製造例からの下記の化合物が、施用量５００ｇ／ｈａで８３％の効力を示す：Ｉａ−７、Ｉａ−１５、Ｉａ−２８、Ｉａ−３２、Ｉａ−４７、Ｉａ−５５、Ｉａ−５６、Ｉａ−５８、Ｉａ−５９、Ｉａ−６４、Ｉａ−７０、Ｉａ−２３５、Ｉｂ−２、Ｉｃ−４、Ｉｃ−４３。

In this test, for example, the following compounds from the preparation examples show 83% potency at an application rate of 500 g / ha: Ia-7, Ia-15, Ia-28, Ia-32, Ia-47, Ia- 55, Ia-56, Ia-58, Ia-59, Ia-64, Ia-70, Ia-235, Ib-2, Ic-4, Ic-43.

  In this test, for example, the following compounds from the preparation examples show 100% efficacy at an application rate of 100 g / ha: Ia-119, Ia-124, Ia-125, Ia-127, Ia-129, Ia- 131, Ia-137, Ia-138, Ia-140, Ia-141, Ia-143, Ia-146, Ia-147, Ia-148, Ia-149, Ia-156, Ia-158, Ia-161, Ia-165, Ia-168, Ia-172, Ia-176, Ia-178, Ia-190, Ia-195, Ia-200, Ia-203, Ia-204, Ia-205, Ia-206, Ia- 207, Ia-208, Ia-210, Ia-211, Ia-212, Ia-213, Ia-214, Ia-215, Ia-219, Ia-225, Ia-226, a-239, Ia-247, Ia-248, Ia-251, Ia-251, Ia-252, Ia-253, Ia-256, Ia-257, Ia-258, Ia-259, Ia-260, Ia- H.264, Ia-266, Ia-267, Ia-270, Ia-271, Ia-272, Ia-273, Ia-274, Ia-275, Ia-276, Ia-277, Ia-278, Ia-278, Ia-279, Ia-280, Ia-281, Ia-282, Ia-282, Ia-284, Ic-26, Ic-27, Ic-29, Ie-1, Ie-2, Ie-3, If- 3

  In this test, for example, the following compounds from the preparation examples show an efficacy of 83% at an application rate of 100 g / ha: Ia-155, Ia-170, Ia-175, Ia-179, Ia-183, Ia- 196, Ia-198, Ia-209, Ia-223, If-2.

Example 16
Phaedon test (PHAECO spray treatment)
Solvent: 78.0 parts by weight of acetone 1.5 parts by weight of dimethylformamide Emulsifier: 0.5 parts by weight of alkylaryl polyglycol ether.

  In order to produce a suitable active ingredient formulation, 1 part by weight of the active ingredient is mixed with a specified amount of solvent and emulsifier and the concentrate is diluted with water containing the emulsifier to the desired concentration. The active ingredient preparation of a desired concentration is sprayed on a disc-shaped slice of Chinese cabbage leaf (Brassica pekinensis), and after drying, larvae of mustard beetle (Phaedon cochleariae) are inhabited.

  After the desired time, the efficacy in% is determined. 100% means that all beetle larvae have died, 0% means that no beetle larvae have died.

  In this test, for example, the following compounds from the preparation examples show 100% efficacy at an application rate of 500 g / ha.

本試験では、例えば、製造例からの下記の化合物が、施用量５００ｇ／ｈａで８３％の効力を示す：Ｉａ−１、Ｉａ−２７、Ｉｂ−３、Ｉｃ−１１、Ｉｃ−２。

In this test, for example, the following compounds from the preparation examples show an efficacy of 83% at an application rate of 500 g / ha: Ia-1, Ia-27, Ib-3, Ic-11, Ic-2.

  In this test, for example, the following compounds from the preparation examples show 100% efficacy at an application rate of 100 g / ha.

実施例１７
アブラムシ（Ｍｙｚｕｓ）試験（ＭＹＺＵＰＥ噴霧処理）
溶媒：７８重量部のアセトン
１．５重量部のジメチルホルムアミド
乳化剤：０．５重量部のアルキルアリールポリグリコールエーテル。

Example 17
Aphid test (MYZUPE spray treatment)
Solvent: 78 parts by weight of acetone 1.5 parts by weight of dimethylformamide Emulsifier: 0.5 parts by weight of alkylaryl polyglycol ether.

  To prepare a suitable active ingredient formulation, 1 part by weight of the active ingredient is mixed with the specified amount of solvent and emulsifier, and the concentrate is diluted with water containing the emulsifier to the desired concentration. The active ingredient formulation of the desired concentration is sprayed onto discoid slices of Chinese cabbage (Brassica pekinensis) with all stages of the peach aphid (Myzus persicae).

  After 6 days, determine the efficacy in%. 100% means that all aphids have died, 0% means that no aphids have died.

  In this test, for example, the following compounds from the preparation examples show 100% efficacy at an application rate of 500 g / ha: Ia-21, Ia-22, Ia-23, Ia-57, Ia-58, Ia- 59, Ia-60, Ia-64, Ia-65, Ia-75, Ia-112.

  In this test, for example, the following compounds from the preparation examples show 90% efficacy at an application rate of 500 g / ha: Ia-36, Ia-41, Ia-55, Ia-63, Ia-67, Ia- 69, Ia-78, Ia-79, Ic-37, Ic-44.

  In this test, for example, the following compounds from the preparation examples show an efficacy of 80% at an application rate of 500 g / ha: Ia-36, Ia-43, Ia-61, Ia-62, Ic-12.

  In this test, for example, the following compounds from the preparation examples show 100% efficacy at an application rate of 100 g / ha: Ia-115, Ia-130, Ia-131, Ia-136, Ia-141, Ia- 142, Ia-143, Ia-150, Ia-153, Ia-155, Ia-156, Ia-160, Ia-162, Ia-163, Ia-164, Ia-169, Ia-170, Ia-174, Ia-175, Ia-184, Ia-190, Ia-195, Ia-252, Ia-256, Ia-276, Ia-277, Ia-278, Ia-279, Ia-280, Ic-26, If- 2.

  In this test, for example, the following compounds from the preparation examples show 90% potency at an application rate of 100 g / ha: Ia-127, Ia-140, Ia-154, Ia-161, Ia-179, Ia- 180, Ia-194, Ia-197, Ia-239, Ia-242, Ia-282, Ic-44, Id-4.

  In this test, for example, the following compounds from the preparation examples show an efficacy of 80% at an application rate of 100 g / ha: Ia-132, Ia-138, Ia-152, Ia-158, Ia-167, Ia- 168, Ia-187, Ia-251, Ia-254.

Example 18
Tetranychus test; OP resistance (TETRUR spray treatment)
Solvent: 78.0 parts by weight of acetone 1.5 parts by weight of dimethylformamide Emulsifier: 0.5 parts by weight of alkylaryl polyglycol ether In order to prepare a suitable active ingredient formulation, 1 part by weight of active ingredient Mix with solvent and emulsifier and dilute the resulting concentrate with water containing emulsifier to the desired concentration. The active ingredient formulation of the desired concentration is sprayed onto the disk-shaped slices of common bean (Phaseolus vulgaris) in which red spider mites (Tetranychus urticae) are developing at all growth stages.

  After 6 days, determine the efficacy (%). 100% means that all red mites have died, 0% means that none of the mites have died.

  In this test, for example, the following compounds from the preparation examples show 100% efficacy at an application rate of 500 g / ha.

本試験では、例えば、製造例からの下記の化合物が、施用量５００ｇ／ｈａで９０％の効力を示す。

In this test, for example, the following compounds from the preparation examples show 90% efficacy at an application rate of 500 g / ha.

本試験では、例えば、製造例からの下記の化合物が、施用量５００ｇ／ｈａで８０％の効力を示す。

In this test, for example, the following compounds from the preparation examples show an efficacy of 80% at an application rate of 500 g / ha.

本試験では、例えば、製造例からの下記の化合物が、施用量１００ｇ／ｈａで１００％の効力を示す。

In this test, for example, the following compounds from the preparation examples show 100% efficacy at an application rate of 100 g / ha.

本試験では、例えば、製造例からの下記の化合物が、施用量１００ｇ／ｈａで９０％の効力を示す。

In this test, for example, the following compounds from the preparation examples show 90% efficacy at an application rate of 100 g / ha.

本試験では、例えば、製造例からの下記の化合物が、施用量１００ｇ／ｈａで８０％の効力を示す。

In this test, for example, the following compounds from the preparation examples show an efficacy of 80% at an application rate of 100 g / ha.

Claims (17)

A compound of the following general formula (I) or a diastereomer, enantiomer, E / Z isomer or salt of the compound.

[Where:
R ¹ is hydrogen, halogen, nitro, cyano, C ₁ -C ₆ -alkyl, C ₂ -C ₆ -alkenyl, which may be mono-substituted or poly-substituted with the same or different ones, C ₂ -C ₆ - _alkynyl, C 1 -C ₆ - _alkoxy, C 1 -C ₆ - _alkylthio, C 1 -C ₆ - _{alkylsulfinyl,} C 1 -C ₆ - _{alkylsulfonyl,} C 3 -C ₆ - cycloalkyl C ₁ -C ₆ -alkylcarbonyl, C ₁ -C ₆ -alkoxyimino-C ₁ -C ₆ -alkyl, C ₁ -C ₆ -alkoxycarbonyl, C ₁ -C ₆ -alkylaminocarbonyl, C ₁ -C ₆ - _{dialkylaminocarbonyl,} C 1 -C ₆ - alkyl _{aminosulfonyl,} C 1 -C ₆ - alkylsulfonylamino, tri _(C 1 -C - alkyl) silyl, aryl, hetaryl, aryl _-C 1 -C ₄ - alkyl or hetaryl _-C 1 -C ₄ - alkyl,
Here, the substituents are independently halogen, cyano, nitro, hydroxyl, C ₁ -C ₆ -alkyl, C ₁ -C ₆ -alkoxy, C ₃ -C ₆ -cycloalkyl, C ₁ -C ₆ -halo. Selected from alkoxy, C ₁ -C ₆ -alkylthio, C ₁ -C ₆ -alkylsulfenyl, C ₁ -C ₆ -alkylsulfonyl, aryl, hetaryl, arylalkyl or hetarylalkyl;
Wherein the aryl, hetaryl, arylalkyl, hetarylalkyl substituents are halogen, cyano, nitro, hydroxyl, C ₁ -C ₆ -alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, C ₃ -C ₆ - or may be monosubstituted by alkylthio - _cycloalkyl, C 1 -C ₆ - _alkoxy, C 1 -C ₆ - _haloalkyl, C 1 -C ₆ - haloalkoxy or _C 1 -C ₆ It may be multi-substituted with the same or different,
Or R ¹ is a C ₁ -C ₄ carbon chain that may contain 1 to 2 heteroatoms from the group consisting of N, S, O, wherein the carbon chain is two adjacent To form an aliphatic, aromatic, heteroaromatic or heterocyclic ring, which may be mono- or polysubstituted by C ₁ -C ₆ -alkyl or halogen, and in this case n Is 2,
n is 1, 2 or 3;
R ² is hydrogen;
R ³ is hydrogen, mono-substituted, or C ₁ -C ₆ -alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C _6- , which may be mono-substituted or the same or different. _alkynyl, C 3 -C ₆ - cycloalkyl, aryl _-C 1 -C ₆ - _alkyl, C 1 -C ₆ - _{alkylcarbonyl,} C 1 -C ₆ - alkylsulfonyl, arylcarbonyl, _{hetarylcarbonyl,} C 1 -C ₆ -alkoxycarbonyl or aryloxycarbonyl,
Wherein said substituents are halogen independently, cyano, nitro, _hydroxyl, C 1 -C ₆ - _alkyl, C 1 -C ₆ - _alkoxy, C 3 -C ₆ - _cycloalkyl, C 1 -C ₆ - _haloalkoxy, C 1 -C ₆ - alkylthio, aryl, hetaryl, arylalkyl, _{hetarylalkyl,} C 1 -C ₄ - alkoxycarbonyl, _{aminocarbonyl,} C 1 -C ₄ - alkylaminocarbonyl or _C 1 -C ₄ - Selected from dialkylaminocarbonyl,
Wherein the aryl, hetaryl, arylalkyl, hetarylalkyl substituents are halogen, cyano, nitro, hydroxyl, C ₁ -C ₆ -alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, C ₃ -C ₆ - or may be monosubstituted by alkylthio - _cycloalkyl, C 1 -C ₆ - _alkoxy, C 1 -C ₆ - _haloalkyl, C 1 -C ₆ - haloalkoxy or _C 1 -C ₆ It may be multi-substituted with the same or different,
V is R ⁴ or is a divalent chemical moiety selected from —O— and —N (R ⁸ ) —, wherein the divalent chemical moiety is Q ⁴ via a single bond. bind to, wherein R ⁴ is hydrogen,
R ⁸ is hydrogen, cyano, hydroxyl, C ₁ -C ₆ -alkyl, C ₂ -C ₆ -alkenyl, C ₂ which may be mono-substituted or poly-substituted with the same or different ones. -C ₆ - _alkynyl, C 3 -C ₆ - _cycloalkyl, C 1 -C ₆ - _alkoxy, C 1 -C ₆ - alkylcarbonyl, arylcarbonyl, _{hetarylcarbonyl,} C 1 -C ₆ - alkoxycarbonyl, arylalkyl Or C ₁ -C ₄ -alkylsulfonyl,
Here, the substituent is independently halogen, cyano, nitro, hydroxyl, C ₁ -C ₆ -alkyl or C ₁ -C ₆ -alkoxy, C ₁ -C ₄ -alkoxycarbonyl, amino, C ₁ -C. ₆ - _alkylamino, C 1 -C ₆ - is selected from alkoxy, - dialkylamino, _{aminocarbonyl,} C 1 -C ₆ - _{alkylaminocarbonyl,} C 1 -C ₆ - dialkylaminocarbonyl and aryl _-C 1 -C ₆
R ⁵ is hydrogen, halogen or C ₁ -C ₆ -alkyl or C ₁ -C ₆ -alkoxy, which may be mono-substituted, poly-substituted with the same or different,
Wherein the substituents are each independently selected from halogen and C ₁ -C ₆ -alkyl;
R ⁶ is hydrogen, halogen, nitro, cyano, amino, hydroxyl, mono-substituted, or C ₁ -C ₆ -alkyl, C ₂ -C, which may be poly-substituted with the same or different ones ₆ - _alkenyl, C 2 -C ₆ - _alkynyl, C 3 -C ₆ - _cycloalkyl, C 1 -C ₆ - _{alkoxy, (C} 1 -C ₆ - alkoxy) _carbonyl, C 1 -C ₆ - alkylamino, formyl , (C ₁ -C ₆ -alkyl) carbonyl, C ₁ -C ₆ -alkoxyimino-C ₁ -C ₆ -alkyl, C ₁ -C ₆ -dialkylamino, (C ₁ -C ₆ -alkylamino) carbonyl, _(C 1 -C ₆ - dialkylamino) _carbonyl, C 1 -C ₆ - _alkylthio, C 1 -C ₆ - _{alkylsulfinyl,} C 1 -C ₆ - alkyl _Sulfonyl, C 1 -C ₆ - alkyl _{aminosulfonyl,} C 1 -C ₆ - alkylsulfonylamino, aryl, hetaryl, aryl _-C 1 -C ₄ - alkyl or hetaryl _-C 1 -C ₄ - alkyl,
Here, the substituents are independently halogen, cyano, nitro, hydroxyl, amino, C ₁ -C ₆ -alkyl, C ₁ -C ₆ -alkoxy, C ₃ -C ₆ -cycloalkyl, C ₁ -C _6. -Haloalkoxy, C ₁ -C ₆ -alkylthio, aryl, hetaryl, arylalkyl or hetarylalkyl;
Wherein the aryl, hetaryl, arylalkyl, hetarylalkyl substituents are halogen, cyano, nitro, hydroxyl, C ₁ -C ₆ -alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, C ₃ -C ₆ - or may be monosubstituted by alkylthio - _cycloalkyl, C 1 -C ₆ - _alkoxy, C 1 -C ₆ - _haloalkyl, C 1 -C ₆ - haloalkoxy or _C 1 -C ₆ Or may be poly-substituted with the same or different,
Or R ⁶ is a C ₁ -C ₄ carbon chain that may contain 1 to 2 heteroatoms from the group consisting of N, S, O, wherein the carbon chain is of Q ⁴ to Q ⁸ Bonded to a position on two adjacent rings to form an aliphatic, aromatic or heteroaromatic ring which may be mono- or polysubstituted by C ₁ -C ₆ -alkyl or halogen, where m Is 2,
m is 0, 1, 2, 3,
X is C ₁ -C ₆ -haloalkyl or C ₃ -C ₆ -halocycloalkyl which may be further mono- or tri-substituted, wherein the substituents are each independently hydroxyl, cyano, C ₁ -C ₄ - _alkoxy, C 1 -C ₄ - _haloalkoxy, C 1 -C ₄ - _{alkoxycarbonyl,} C 1 -C ₄ - alkylaminocarbonyl and _C 1 -C ₄ - is selected from dialkylaminocarbonyl,
W is O or S;
AY is hetaryl, heterocycle or oxoheterocycle which may be cyano together or mono- or poly-substituted,
Here, the substituent is a halogen, nitro, cyano, amino, hydroxyl, which may be mono-substituted or the same or different, and may be poly-substituted amino, C ₁ -C ₆ -alkyl, C ₁ -C ₆ - _alkoxy, C 1 -C ₆ - alkoxy _-C 1 -C ₆ - _alkyl, C 1 -C ₆ - _{alkylcarbonyl,} C 2 -C ₆ - _alkenyl, C 2 -C ₆ - alkynyl, _{C 3} -C ₆ - cycloalkyl, aryl, _hetaryl, C 1 -C ₆ - _arylalkyl, C 1 -C ₆ - hetarylalkyl, aryloxy, hetaryloxy, _sulfonyl, C 1 -C ₆ - alkylthio, _{C 1} - C ₆ - _{alkylsulfinyl,} C 1 -C ₆ - _{alkylsulfonyl, C} 1 -C 6 _- alkoxycarbonyl or _C 1 -C ₆ - A Selected from rualkylaminocarbonyl,
Here, each of the substituents is independently halogen, nitro, cyano, C ₁ -C ₆ -alkyl, C ₁ -C ₆ -haloalkyl, C ₁ -C ₆ -alkoxy, C ₁ -C ₆ -haloalkoxy, C ₃ -C ₆ - _cycloalkyl, C 3 -C ₆ - _{cycloalkylcarbonyl,} C 1 -C ₆ - _alkylthio, C 1 -C ₆ - _{alkylsulfinyl,} C 1 -C ₆ - _{alkylsulfonyl, (C} 1 -C ₆ - alkoxy) _carbonyl, C 2 -C ₆ - _alkenyl, C 2 -C ₆ - _alkynyl, C 1 -C ₆ - _alkylamino, C 3 -C ₆ - _{cycloalkylamino, (C} 1 -C ₆ - alkyl) C ₃ -C ₆ - is selected from cycloalkylamino or di _(C 1 -C ₄₎ alkylamino,
Or A is a moiety —NR ¹³ C (═O) —, —NR ¹³ C (═S) —, —C (R ¹¹ ) (R ¹² ) NR ¹³ C (═O) —, —C (R ¹¹ ) (U) NR ¹³ C (═O) —, —C (R ¹¹ ) (R ¹² ) N (U) C (═O) —, —C (R ¹¹ ) (R ¹² ) NR ¹³ C (= S) ^{-, - C (= O)} NR 13 -, - C (= O) NR 13 CH 2 -, - C (= S) NR 13 -, - C (= S) NR 13 CH 2 -, - C (= O) NR ¹³ C (R ¹¹ ) = N—O—, —C (R ¹¹ ) = N—O—, —C (NH ₂ ) = N—O—, —C (R ¹¹ ) = N—OCH ₂ ^{C (= O) NR 13 -} , - C (R 11) (R 12) NR 13 C (= O) NR 14 -, - C (R 11) (R 12) NR 13 C (= O) CH 2 S ^-, - ^NR 13 (C ^{O) NR 14 -, - C} (= O) -, - C (= N-O-R 13) -, - C (= O) O -, - C (= O) OCH 2 C (= O) - ^{_{, -C (= O) OCH 2}} C (= O) NR 13 -, - C (= O) NR 13 CH 2 C (= O) NR 14 -, - C (= O) NR 13 CH 2 C (= O) —, —C (═O) NR ¹³ CH ₂ C (═O) O—, —C (═O) NR ¹³ NR ¹⁴ C (═O) —, —C (═O) NR ¹³ NR ¹⁴ — ^{, -N (R 13) -,} - C (R 11) (R 12) NR 13 -, - S (= O) p -, - S (= O) 2 NR 13 -, - NR 13 S (= O ) _2- , -C (R ¹¹ ) (R ¹² ) NR ¹³ S (= O) _2- , -SO (= N-CN)-, -S (= N-CN)-, -C (= O) _{NHS (= O) 2 -,} - C (= O) N ( ^{13) -O -, - C (} = O) CH (CN) - or -CH (CN) ^{NR 13} - a divalent chemical moiety selected from wherein, the in the chemical portion of the divalent 1 's (left) linking site, ring at one portion in Q ⁸ from the position Q ⁴ in each case, the second (right) connecting portion is connected to Y in each case, wherein U is together with the carbon atom adjacent to the linking site a of the ring Q ⁸ from the position Q ^4, optionally substituted to form a 5 to 7-membered ring C ₂ -C 4 _- alkyl,
Wherein said substituents are each independently _C 1 -C ₃ - is selected from alkoxy and halogen, - _alkyl, C 1 -C ₃
p may take values of 0, 1 or 2;
R ¹¹ and R ¹² are each independently hydrogen, cyano or mono-substituted, or C ₁ -C ₄ -alkyl or C ₃ -C _6- which may be poly-substituted with the same or different ones. Cycloalkyl,
Wherein the substituents are each independently selected from halogen, cyano, nitro, hydroxyl, C ₁ -C ₆ -alkyl and C ₁ -C ₆ -alkoxy,
Or R ¹¹ and R ¹² together may have 1 to 2 double bonds and may form a 3 to 6 membered ring, C ₂ -C ₅ -alkyl or C ₃ -C ₅ -Alkenyl,
Alternatively R ¹¹ and ^{R 13} are, _C 2 -C ₅ forming two double bonds contain an 3 to 7-membered ring may be from 1 together - alkyl or _C 3 -C ₅ - Alkenyl,
R ¹³ and R ¹⁴ are each independently hydrogen, C ₁ -C ₆ -alkyl or C ₃ -C which may be mono-substituted, or may be poly-substituted with the same or different ones. ₆ -cycloalkyl, C ₁ -C ₆ -alkylcarbonyl, C ₁ -C ₆ -alkoxycarbonyl or aryloxycarbonyl,
Wherein the substituents are each independently selected from halogen, cyano, nitro, hydroxyl, C ₁ -C ₆ -alkyl or C ₁ -C ₆ -alkoxy,
Or R ¹³ and R ¹⁴ together may have 1 to 2 double bonds and form a 3 to 7-membered ring C ₂ -C ₅ -alkyl or C ₃ -C ₅ -Alkenyl,
Y is hydrogen, mono-substituted, or C ₁ -C ₆ -alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl which may be the same or different and multi-substituted. C ₃ -C ₆ -cycloalkyl, C ₃ -C ₆ -cycloalkenyl, aryl, hetaryl, heterocycle or oxoheterocycle,
Here, the substituent is halogen, nitro, cyano, hydroxyl, which may be mono-substituted or the same or different and may be poly-substituted amino, C ₁ -C ₆ -alkyl, C _2- C ₆ - _alkenyl, C 2 -C ₆ - _alkynyl, C 3 -C ₆ - _cycloalkyl, C 1 -C ₆ - _{alkylcarbonyl,} C 1 -C ₆ - _alkoxy, C 1 -C ₆ - alkoxycarbonyl, _{C 1} -C ₆ - _alkylthio, C 1 -C ₆ - _{alkylsulfinyl,} C 1 -C ₆ - _{alkylsulfonyl,} C 1 -C ₆ - _{alkoxycarbonyl,} C 1 -C ₆ - _{alkylaminocarbonyl,} C 1 -C ₆ - dialkyl _{aminocarbonyl,} C 1 -C ₆ - alkyl _{aminosulfonyl,} C 1 -C ₆ - alkylsulfonylamino, aryl, f _Reel, C 1 -C ₆ - _arylalkyl, C 1 -C ₆ - hetarylalkyl, aryloxy, hetaryloxy or _{heterocyclic,} C 1 -C ₆ - _alkoxy, C 1 -C ₆ - alkyl, _{C 1} - C
₆ - is selected from alkoxycarbonyl, - alkylcarbonyl, sulfonyl, _sulfinyl, C 1 -C ₆ - alkylthio or _C 1 -C ₆
Here, each of the substituents is independently halogen, C ₁ -C ₆ -alkyl, hydroxyl, amino, C ₁ -C ₆ -alkylcarbonyl, C ₁ -C ₆ -haloalkyl, C ₁ -C ₆ -alkoxy, C ₁ -C ₆ - _haloalkoxy, C 3 -C ₆ - _cycloalkyl, C 3 -C ₆ - cycloalkylcarbonyl, cyano, _nitro, C 1 -C ₆ - _alkylthio, C 1 -C ₆ - alkylsulfinyl, _{C 1} -C ₆ - _{alkylsulfonyl, (C} 1 -C ₆ - alkoxy) _carbonyl, C 2 -C ₆ - _alkenyl, C 2 -C ₆ - _alkynyl, C 1 -C ₆ - _alkylamino, C 3 -C ₆ - cycloalkyl Alkylamino, (C ₁ -C ₆ -alkyl) C ₃ -C ₆ -cycloalkylamino, di (C ₁ -C ₄ ) alkylamino or C ₁ -C ₆ - is selected from alkyl aminocarbonyl,
Q ¹ to Q ³ are each independently a carbon atom substituted with hydrogen or R ¹ ,
Q ⁴ is hydrogen or a carbon atom substituted by R ⁶ or bonded to V (in which case V is other than R ⁴ );
Q ⁵ to Q ⁸ are each independently a carbon atom substituted by hydrogen, R ⁶ or A-Y, and exactly one of Q ⁵ , Q ⁶ , Q ⁷ , Q ⁸ is A-Y Has been replaced by ] R ¹ is hydrogen, halogen, nitro, cyano, C ₁ -C ₄ -alkyl, C ₂ -C ₆ -alkenyl, which may be monosubstituted or polysubstituted with the same or different ones, C ₂ -C ₄ - _alkynyl, C 1 -C ₄ - _alkoxy, C 1 -C ₄ - _alkylthio, C 1 -C ₄ - _{alkylsulfinyl,} C 1 -C ₄ - _{alkylsulfonyl,} C 3 -C ₄ - cycloalkyl C ₁ -C ₄ -alkylcarbonyl, C ₁ -C ₄ -alkoxycarbonyl, C ₁ -C ₄ -alkylaminocarbonyl, C ₁ -C ₄ -dialkylaminocarbonyl or C ₁ -C ₄ -alkylaminosulfonyl ,
Wherein said substituents are independently halogen, cyano, nitro, _hydroxyl, C 1 -C ₄ - _alkyl, C 1 -C ₄ - _alkoxy, C 3 -C ₄ - _cycloalkyl, C 1 -C ₄ - haloalkoxy and _C 1 -C ₄ - is selected from alkylthio,
n is 1, 2 or 3,
R ² is hydrogen;
R ³ is hydrogen, or may be monosubstituted, or the same or different at polysubstituted _C 1 may also be -C ₄ - _alkyl, C 2 -C ₄ - _alkenyl, C 2 -C ₄ - _alkynyl, C 3 -C ₄ - cycloalkyl, aryl _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - _{alkylcarbonyl,} C 1 -C ₄ - alkylsulfonyl, arylcarbonyl, _{hetarylcarbonyl,} C 1 -C ₄ -alkoxycarbonyl or aryloxycarbonyl,
Wherein said substituents are halogen independently, cyano, nitro, _hydroxyl, C 1 -C ₆ - _alkyl, C 1 -C ₆ - _alkoxy, C 3 -C ₆ - _cycloalkyl, C 1 -C ₆ - _haloalkoxy, C 1 -C ₆ - _alkylthio, C 1 -C ₄ - alkoxycarbonyl, _{aminocarbonyl,} C 1 -C ₄ - alkylaminocarbonyl and _C 1 -C ₄ - is selected from dialkylaminocarbonyl,
V is R ⁴ or a divalent chemical moiety selected from —O— and —N (R ⁸ ) —, wherein
The divalent chemical moiety is attached to Q ⁴ via a single bond , where
R ⁴ is hydrogen;
R ⁸ may be hydrogen, cyano, hydroxyl, mono-substituted or C ₁ -C ₄ -alkyl, C ₂ -C ₆ -alkenyl, C ₂ which may be mono-substituted or the same or different. -C ₆ - _alkynyl, C 3 -C ₆ - alkylcarbonyl, - _cycloalkyl, C 1 -C ₄ - _alkoxy, C 1 -C ₆ - alkoxycarbonyl, arylalkyl or _C 1 -C ₄
Here, the substituents are each independently halogen, cyano, nitro, hydroxyl, C ₁ -C ₆ -alkyl, C ₁ -C ₆ -alkoxy, C ₁ -C ₄ -alkoxycarbonyl, aminocarbonyl, C _1. -C ₄ - alkylaminocarbonyl or _C 1 -C ₄ - dialkylaminocarbonyl and aryl _-C 1 -C ₄ - alkoxy,
R ⁵ is hydrogen, halogen, or C ₁ -C ₄ -alkyl which may be mono-substituted or poly-substituted with the same or different, wherein the substituents are each independently Selected from halogen, C ₁ -C ₄ -alkyl or C ₁ -C ₄ -alkoxy,
R ⁶ may be hydrogen, halogen, nitro, cyano, amino, hydroxyl, monosubstituted or polysubstituted with the same or different, C ₁ -C ₄ -alkyl, C ₂ -C ₄ - _alkenyl, C 2 -C ₄ - _alkynyl, C 3 -C ₅ - _cycloalkyl, C 1 -C ₄ - _{alkoxy, (C} 1 -C ₄ - alkoxy) _carbonyl, C 1 -C ₄ - alkylamino, formyl , _(C 1 -C ₄ - alkyl) _carbonyl, C 1 -C ₄ - alkoxyimino _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - _{dialkylamino, (C} 1 -C ₄ - alkylamino) carbonyl, _(C 1 -C ₄ - dialkylamino) _carbonyl, C 1 -C ₄ - _alkylthio, C 1 -C ₄ - _{alkylsulfinyl,} C 1 -C ₄ - alkyl _Sulfonyl, C 1 -C ₄ - alkyl sulfonylamino, - alkylaminosulfonyl or _C 1 -C ₄
Here, the substituents are independently halogen, cyano, nitro, hydroxyl, amino, C ₁ -C ₆ -alkyl, C ₁ -C ₆ -alkoxy, C ₃ -C ₆ -cycloalkyl, C ₁ -C. ₆ - haloalkoxy and _C 1 -C ₆ - is selected from alkylthio,
Or R ⁶ is a C ₁ -C ₄ carbon chain that may contain 1 to 2 heteroatoms from the group consisting of N, S, O, wherein the carbon chain is two adjacent bound to Q ⁸ from the position Q ⁴ on the ring, C 1 _-C 6 _- alkyl or aliphatic which is optionally monosubstituted or polysubstituted by halogen, to form an aromatic or heteroaromatic ring,,, In this case, m is 2,
m is 0, 1, 2, 3;
X is C ₁ -C ₄ -haloalkyl or C ₃ -C ₅ -halocycloalkyl, which may be further mono- to tri-substituted by hydroxyl, cyano or C ₁ -C ₄ -alkoxy,
W is O or S;
AY together is cyano or pyrrolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, pyrazolyl, imidazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl, 1,2, 3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,3,4-oxadiazolyl, 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,3,4-thiadiazolyl, tetrazolyl, pyridyl, pyrimidinyl, Pyridazinyl, pyrazinyl, 1,2,4-triazinyl, 1,3,5-triazinyl, pyrrolidinyl, isoxazolidinyl, pyrazolidinyl, oxazolidinyl, thiazolidinyl, imidazolinyl, imidazolidinyl, 1,2,4-oxadiazolidinyl, 1 , 2,4-thiadiazolidini 1,2,4-triazolidinyl, 1,3,4-oxadiazolidinyl, 1,3,4-thiadiazolidinyl, 1,3,4-triazolidinyl, pyrrolinyl, isoxazolinyl, 2,3- Dihydropyrazolyl, 3,4-dihydropyrazolyl, 4,5-dihydropyrazolyl, 2,3-dihydrooxazolyl, 3,4-dihydrooxazolyl, piperidinyl, oxopyrrolidinyl, 3-oxo-1,2, May be mono- or polysubstituted from the group of 4-triazolidinyl, 5-oxo-1,2,4-triazolidinyl, dioxopyrrolidinyl, oxomorpholinyl, oxopiperidinyl and oxopiperazinyl A heterocycle or oxoheterocycle,
Here, the substituent is a halogen, nitro, cyano, amino, hydroxyl, which may be mono-substituted or the same or different, and may be poly-substituted amino, C ₁ -C ₆ -alkyl, C ₁ -C ₆ - _alkoxy, C 1 -C ₆ - alkoxy _-C 1 -C ₆ - _alkyl, C 1 -C ₆ - _{alkylcarbonyl,} C 2 -C ₆ - _alkenyl, C 2 -C ₆ - alkynyl, _{C 3} -C ₆ - cycloalkyl, aryl, _hetaryl, C 1 -C ₆ - _arylalkyl, C 1 -C ₆ - hetarylalkyl, aryloxy, _hetaryloxy, C 1 -C ₆ - _alkylthio, C 1 -C ₆ - _{alkylsulfinyl,} C 1 -C ₆ - _{alkylsulfonyl,} C 1 -C ₆ - alkoxycarbonyl and _C 1 -C ₆ - alkylamino Is selected from carbonyl,
Here, each of the substituents is independently halogen, nitro, cyano, C ₁ -C ₆ -alkyl, C ₁ -C ₆ -haloalkyl, C ₁ -C ₆ -alkoxy, C ₁ -C ₆ -haloalkoxy, C ₃ -C ₆ - _cycloalkyl, C 3 -C ₆ - _{cycloalkylcarbonyl,} C 1 -C ₆ - _alkylthio, C 1 -C ₆ - _{alkylsulfinyl,} C 1 -C ₆ - _{alkylsulfonyl, (C} 1 -C ₆ - alkoxy) _carbonyl, C 2 -C ₆ - _alkenyl, C 2 -C ₆ - _alkynyl, C 1 -C ₆ - _alkylamino, C 3 -C ₆ - _{cycloalkylamino, (C} 1 -C ₆ - alkyl) C ₃ -C ₆ - is selected from cycloalkylamino or di _(C 1 -C ₄₎ alkylamino,
Or A is a moiety —NR ¹³ C (═O) —, —NR ¹³ C (═S) —, —C (R ¹¹ ) (R ¹² ) NR ¹³ C (═O) —, —C (R ¹¹ ) (U) NR ¹³ C (═O) —, —C (R ¹¹ ) (R ¹² ) NR ¹³ C (═S) —, —C (═O) NR ¹³ —, —C (═O) N (R _{^{13) -O -, - C (}} = O) NR 13 CH 2 -, - C (= S) NR 13 -, - C (= S) NR 13 CH 2 -, - C (= O) NR 13 CH = N—O—, —C (R ¹¹ ) ═N—O—, —C (NH ₂ ) = N—O—, —C (R ¹¹ ) = N—OCH ₂ C (═O) NR ¹³ —, — C (R ¹¹ ) (R ¹² ) NR ¹³ C (═O) NR ¹⁴ —, —C (R ¹¹ ) (R ¹² ) NR ¹³ C (═O) CH ₂ S—, —NR ¹³ (C═O) NR ¹⁴ -, - C ( ═O) —, —C (═N—O—R ¹³ ) —, —C (═O) O—, —C (═O) OCH ₂ C (═O) NR ¹³ —, —C (═O) _{^{OCH 2 C (= O) NH}} -, - C (= O) NR 13 CH 2 C (= O) NR 14 -, - C (= O) NR 13 CH 2 C (= O) -, - C (= O) NR ¹³ CH ₂ C (═O) O—, —C (═O) NR ¹³ NR ¹⁴ C (═O) —, —C (═O) NR ¹³ NR ¹⁴ —, —N (R ¹³ ) — , —C (R ¹¹ ) (R ¹² ) NR ¹³ —, —S (═O) _p —, —S (═O) ₂ NR ¹³ —, —NR ¹³ S (═O) ₂ —, —C (R ¹¹ ) (R ¹² ) NR ¹³ S (═O) ₂ —, —C (═O) CH (CN) — or —CH (CN) NR ¹³ —, In the chemical part of the valence The first (left) linking site is in each case linked to the ring at any of positions Q ⁴ to Q ⁸ and the second (right) linking site is linked to Y in each case, where p is 0 A substitution of which U forms a 5- to 6-membered ring with the carbon atom adjacent to the linking site of A on the ring at positions Q ⁴ to Q ⁸ at a value of 1 or 2 C ₂ -C ₄ -alkyl, which may be
Wherein the substituents are each independently selected from halogen, C ₁ -C ₃ -alkyl and C ₁ -C ₃ -alkoxy,
R ¹¹ and R ¹² are each independently C ₁ -C ₄ -alkyl or C ₃ -C ₆ -cycloalkyl optionally substituted with the same or different from hydrogen, cyano or mono-substitution,
Wherein the substituents are each independently selected from halogen, cyano, nitro, hydroxyl, C ₁ -C ₆ -alkyl or C ₁ -C ₆ -alkoxy,
Or R ¹¹ and is ^{R 12} is an integral, _C 2 -C forming two double bonds comprise been 3 to 6-membered ring may be from 1 ₅ - alkyl or _C 3 -C ₅ - Alkenyl,
Or R ¹¹ and R ¹³ together form a C ₂ -C ₅ -alkyl or C ₃ -C _5- forming a 3- to 7-membered ring which may contain 1 to 2 double bonds Alkenyl,
R ¹³ and R ¹⁴ are each independently hydrogen, mono-substituted, or C ₁ -C ₄ -alkyl or C ₃ -C ₆ -cycloalkyl optionally substituted or the same or different. C ₁ -C ₄ -alkylcarbonyl, C ₁ -C ₄ -alkoxycarbonyl or aryloxycarbonyl,
Wherein the substituents are each independently selected from halogen, cyano, nitro, hydroxyl, C ₁ -C ₄ -alkyl and C ₁ -C ₄ -alkoxy,
Or R ¹³ and R ¹⁴ are combined to form a C ₇ -C ₅ -alkyl or C ₃ -C _5- forming a 3- to 7-membered ring which may contain 1 to 2 double bonds Alkenyl,
Y may be hydrogen or mono-substituted, or may be poly-substituted with the same or different C ₁ -C ₆ -alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C _6- Alkynyl, C ₃ -C ₆ -cycloalkyl, C ₃ -C ₆ -cycloalkenyl, or phenyl that may be mono-substituted or the same or different and poly-substituted, or thienyl , Furanyl, pyrrolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, pyrazolyl, imidazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl, 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1 , 3,4-oxadiazolyl, 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1, , 4-thiadiazolyl, tetrazolyl, pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, 1,2,4-triazinyl, 1,3,5-triazinyl, pyrrolidinyl, isoxazolidinyl, pyrazolidinyl, oxazolidinyl, thiazolidinyl, imidazolidinyl, 1,2 , 4-oxadiazolidinyl, 1,2,4-thiadiazolidinyl, 1,2,4-triazolidinyl, 1,3,4-oxadiazolidinyl, 1,3,4-thiadiazolidinyl, 1 , 3,4-triazolidinyl, pyrrolinyl, isoxazolinyl, 2,3-dihydropyrazolyl, 3,4-dihydropyrazolyl, 4,5-dihydropyrazolyl, 2,3-dihydrooxazolyl, 3,4-dihydrooxa Zolyl, piperidinyl, tetrahydrothienyl, piperazinyl, mole Folinyl, thiomorpholinyl, dihydropyranyl, tetrahydropyranyl, tetrahydrothienyl, 1,4-dioxanyl, 1,3-dioxanyl, dioxolanyl, dioxolyl, tetrahydrofuranyl, dihydrofuranyl, oxetanyl, thietanyl, oxide thietanyl, dioxide thietanyl From the group of, oxiranyl, azetidinyl, oxoazetidinyl, oxaziridinyl, oxazepanyl, oxadinanyl, azepanyl, oxopyrrolidinyl, dioxopyrrolidinyl, oxomorpholinyl, oxopiperidinyl, oxopiperazinyl or oxotetrahydrofuranyl A mono- or poly-substituted heterocyclic ring,
Here, the substituent is amino, C ₁ -C ₆ -alkyl, C, which may be mono-substituted from halogen, nitro, cyano or hydroxyl, or may be poly-substituted with the same or different ones. ₁ -C ₆ - _alkoxy, C 1 -C ₆ - alkoxy _-C 1 -C ₆ - _alkyl, C 1 -C ₆ - _{alkylcarbonyl,} C 2 -C ₆ - _alkenyl, C 2 -C ₆ - alkynyl, _{C 3} -C ₆ - cycloalkyl, aryl, _hetaryl, C 1 -C ₆ - _arylalkyl, C 1 -C ₆ - hetarylalkyl, aryloxy, _hetaryloxy, C 1 -C ₆ - _alkylthio, C 1 -C ₆ - _{alkylsulfinyl,} C 1 -C ₆ - _{alkylsulfonyl,} C 1 -C ₆ - is selected from alkoxycarbonyl or heterocyclic,
Here, the substituent is independently halogen, nitro, hydroxyl, amino, cyano, C ₁ -C ₆ -alkyl, C ₁ -C ₆ -alkylcarbonyl, C ₁ -C ₆ -haloalkyl, C ₁ -C. ₆ - _alkoxy, C 1 -C ₆ - _haloalkoxy, C 3 -C ₆ - _cycloalkyl, C 3 -C ₆ - _{cycloalkylcarbonyl,} C 1 -C ₆ - _alkylthio, C 1 -C ₆ - alkylsulfinyl, C ₁ -C ₆ - _{alkylsulfonyl, (C} 1 -C ₆ - alkoxy) _carbonyl, C 2 -C ₆ - _alkenyl, C 2 -C ₆ - _alkynyl, C 1 -C ₆ - _alkylamino, C 3 -C ₆ - Cycloalkylamino, (C ₁ -C ₆ -alkyl) C ₃ -C ₆ -cycloalkylamino, di (C ₁ -C ₄ ) alkylamino or C ₁ -C ₆ - it may be selected from alkyl aminocarbonyl,
Q ¹ to Q ³ are each independently a carbon atom substituted by hydrogen or R ¹ ;
Q ⁴ is hydrogen or a carbon atom substituted by R ⁶ or bonded to V (in which case V is other than R ⁴ );
Q ⁵ to Q ⁸ are each independently a carbon atom substituted by hydrogen, R ⁶ or A-Y, and exactly one of Q ⁵ , Q ⁶ , Q ⁷ , Q ⁸ is A-Y A substituted compound of general formula (I) according to claim 1 or a diastereomer, enantiomer, E / Z isomer or salt of said compound. R ¹ is hydrogen, halogen, nitro, cyano, C ₁ -C ₄ -alkyl, C ₁ -C ₄ -alkoxy, which may be monosubstituted or polysubstituted with the same or different ones, C ₁ -C ₄ - _alkylthio, C 1 -C ₄ - _{alkylsulfinyl,} C 1 -C ₄ - _{alkylsulfonyl,} C 1 -C ₄ - _{alkylcarbonyl,} C 1 -C ₄ - _{alkoxycarbonyl,} C 1 -C ₄ - Alkylaminocarbonyl, C ₁ -C ₄ -dialkylaminocarbonyl or C ₁ -C ₄ -alkylaminosulfonyl,
Wherein said substituents are independently halogen, cyano, nitro, _hydroxyl, C 1 -C ₄ - _alkyl, C 1 -C ₄ - _alkoxy, C 3 -C ₄ - _cycloalkyl, C 1 -C ₄ - Selected from haloalkoxy or C ₁ -C ₄ -alkylthio;
n is 1, 2 or 3,
R ² is hydrogen;
R ³ is hydrogen, or may be monosubstituted, or the same or different at polysubstituted _C 1 may also be -C ₄ - _alkyl, C 2 -C ₄ - _alkenyl, C 2 -C ₄ - Alkynyl, C ₁ -C ₄ -alkylcarbonyl, C ₁ -C ₄ -alkylsulfonyl, C ₁ -C ₄ -alkoxycarbonyl or aryloxycarbonyl,
Wherein the substituents are each independently selected from halogen, cyano, nitro, hydroxyl, C ₁ -C ₆ -alkyl, C ₁ -C ₆ -alkoxy or C ₁ -C ₄ -alkoxycarbonyl,
V is R ⁴ or a divalent chemical moiety selected from —O— and —N (R ⁸ ) — attached to Q ⁴ via a single bond, wherein R ⁴ is hydrogen And
R ⁸ is hydrogen, cyano, hydroxyl, C ₁ -C ₄ -alkyl, C ₂ -C ₄ -alkenyl, C ₃ -C, which may be mono-substituted or the same or different and may be poly-substituted. ₄ - alkynyl, aryl _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - _alkoxy, C 1 -C ₆ - alkoxycarbonyl or _C 1 -C ₄ - alkylcarbonyl,
Here, each of the substituents is independently halogen, cyano, nitro, hydroxyl, C ₁ -C ₆ -alkyl, C ₁ -C ₆ -alkoxy, C ₁ -C ₄ -alkoxycarbonyl, aminocarbonyl, C _1- C ₄ - _{alkylaminocarbonyl,} C 1 -C ₄ - is selected from alkoxy, - dialkylaminocarbonyl or aryl _-C 1 -C ₄
R ⁵ is an optionally trisubstituted by identical or different and hydrogen or monosubstituted C ₁ -C 4 _- alkyl, wherein said substituents are each independently halogen, C ₁ -C ₄ - It is selected from alkoxy, - alkyl or _C 1 -C ₄
R ⁶ is hydrogen, halogen, nitro, cyano, C ₁ -C ₄ -alkyl, C ₂ -C ₄ -alkynyl, which may be mono-substituted or poly-substituted with the same or different, C ₁ -C ₄ - _{alkoxy, (C} 1 -C ₄ - alkyl) _{carbonyl, (C} 1 -C ₄ - alkylamino) _{carbonyl, (C} 1 -C ₄ - dialkylamino) _carbonyl, C 1 -C ₄ - alkylthio , _C 1 -C ₄ - _{alkylsulfinyl,} C 1 -C ₄ - alkyl sulfonylamino, - _{alkylsulfonyl,} C 1 -C ₄ - alkylaminosulfonyl or _C 1 -C ₄
Wherein the substituents are each independently halogen, cyano, nitro, C ₁ -C ₆ -alkyl, C ₁ -C ₆ -alkoxy, C ₁ -C ₆ -haloalkoxy and C ₁ -C ₆ -alkylthio. Selected
Or R _{^6, -OCH 2 O -, - OCF} 2 O -, - OCH 2 CH 2 O -, - OCF 2 CF 2 O- or -CH = CH-CH = is CH-, wherein said substituted The group forms a ring via two adjacent groups each selected from Q ⁴ to Q ⁸ ;
m is 0, 1, 2, 3;
X is C ₁ -C ₄ -haloalkyl or C ₃ -C ₅ -halocycloalkyl, which may be further mono to trisubstituted by hydroxyl, cyano or C ₁ -C ₄ -alkoxy,
W is O,
AY together is cyano or may be mono- or polysubstituted pyrrolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, pyrazolyl, imidazolyl, 2-imidazolinyl, 1,2,3-triazolyl, 1,2,4-triazolyl, 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,3,4-oxadiazolyl, 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1, A heterocyclic ring from the group of 3,4-thiadiazolyl, tetrazolyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, 1,2,4-triazinyl and 1,3,5-triazinyl;
Here, the substituent is halogen, nitro, cyano, hydroxyl, which may be mono-substituted or the same or different, and may be poly-substituted amino, C ₁ -C ₄ -alkyl, C _1- C ₄ - _alkoxy, C 1 -C ₄ - alkoxy _-C 1 -C ₄ - _alkyl, C 2 -C ₄ - _alkynyl, C 1 -C ₆ - _alkylthio, C 1 -C ₆ - _{alkylsulfinyl,} C 1 -C ₆ - _{alkylsulfonyl,} C 3 -C ₆ - cycloalkyl, aryl and hetaryl,
Here, the substituent is independently halogen, hydroxyl, amino, nitro, cyano, C ₁ -C ₆ -alkyl, C ₁ -C ₆ -haloalkyl, C ₁ -C ₆ -alkoxy, C ₁ -C _6. - _haloalkoxy, C 3 -C ₆ - _cycloalkyl, C 3 -C ₆ - _{cycloalkylcarbonyl,} C 1 -C ₆ - _alkylthio, C 1 -C ₆ - _{alkylsulfinyl,} C 1 -C ₆ - alkylsulfonyl, ( C ₁ -C _6- alkoxy) _carbonyl, C 2 -C ₆ - _alkenyl, C 2 -C ₆ - _alkynyl, C 1 -C ₆ - _alkylamino, C 3 -C ₆ - _{cycloalkylamino, (C} 1 -C ₆ - _alkyl) C 3 -C ₆ - cycloalkylamino, di _(C 1 -C ₄₎ alkylamino or _C 1 -C ₆ - alkylamino carbonylation It is selected from,
A is a moiety —NR ¹³ C (═O) —, —C (R ¹¹ ) (R ¹² ) NR ¹³ C (═O) —, —C (═O) O—, —C (R ¹¹ ) (U ) NR < ¹³ > C (= O)-, -C (R < ¹¹ >) (R < ¹² >) N (U) C (= O)-, -C (= O) NR < ¹³ >-, -C (= O) N (R ¹³ ) —O—, —C (═O) NR ¹³ CH ₂ —, —C (═O) NR ¹³ CH═N—O—, —C (R ¹¹ ) = N—O—, —C (R ¹¹ ) = N—OCH ₂ C (═O) NR ¹³ —, —C (R ¹¹ ) (R ¹² ) NR ¹³ C (═O) NR ¹⁴ —, —C (R ¹¹ ) (R ¹² ) NR ¹³ C ( ═O) CH ₂ S—, —NR ¹³ (C═O) NR ¹⁴ —, —C (═O) —, —C (═N—O—R ¹³ ) —, —C (═O) NR ¹³ CH ^{_{2 C (= O) NR 14}} -, - C (= _{^{) NR 13 CH 2 C (=}} O) -, - C (= O) NR 13 CH 2 C (= O) O -, - C (= O) NR 13 NR 14 C (= O) -, - C ( ═O) NR ¹³ NR ¹⁴ —, —N (R ¹³ ) —, —C (R ¹¹ ) (R ¹² ) NR ¹³ —, —S (═O) _p —, —S (═O) ₂ NR ¹³ — , —NR ¹³ S (═O) ₂ —, —C (R ¹¹ ) (R ¹² ) NR ¹³ S (═O) ₂ —, C (═O) CH
(CN) - or -CH (CN) ^{NR 13} - a divalent chemical moiety selected from the first (left) ligation site in the chemical part of the bivalent in each case, Q from the position ^{Q 4 In} one of the ^{8 to} the ring, the second (right-hand) linking site is in each case linked to Y, where p may take the values 0, 1 or 2 and in U, together with the carbon atom adjacent to the connecting site a on ring Q ⁸ from the position Q ^4, optionally substituted 5 to form a 6-membered ring C ₂ -C 4 _- an alkyl ,
Wherein the substituents are each independently selected from C ₁ -C ₃ -alkyl and halogen, and wherein R ¹¹ and R ¹² are each independently hydrogen, C ₁ -C ₄ -alkyl or C ₁ -C ₄ - haloalkyl,
Or R ¹¹ and is ^{R 12} is an integral, _C 2 -C forming two double bonds comprise been 3 to 6-membered ring may be from 1 ₅ - alkyl or _C 3 -C ₅ - Alkenyl,
Or R ¹¹ and R ¹³ together form a C ₂ -C ₅ -alkyl or C ₃ -C _5- forming a 3- to 7-membered ring which may contain 1 to 2 double bonds Alkenyl, and wherein R ¹³ and R ¹⁴ are each independently hydrogen, C ₁ -C ₄ -alkyl, which may be monosubstituted or optionally polysubstituted with the same or different C ₃ -C ₆ - _cycloalkyl, C 1 -C ₄ - alkyl, aryloxycarbonyl or _C 1 -C ₄ - alkoxycarbonyl,
Wherein the substituents are each independently selected from halogen, cyano, C ₁ -C ₄ -alkyl and C ₁ -C ₄ -alkoxy,
Or R ¹³ and R ¹⁴ are combined to form a C ₇ -C ₅ -alkyl or C ₃ -C _5- forming a 3- to 7-membered ring which may contain 1 to 2 double bonds Alkenyl,
Y may be hydrogen or mono-substituted, or C ₁ -C ₆ -alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl optionally substituted or the same or different. C ₃ -C ₆ -cycloalkyl, C ₃ -C ₆ -cycloalkenyl, which may be mono-substituted or phenyl which may be the same or different and poly-substituted, or thienyl, Furanyl, pyrrolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, pyrazolyl, imidazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl, 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1, 3,4-oxadiazolyl, 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,3 4-thiadiazolyl, tetrazolyl, pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, 1,2,4-triazinyl, 1,3,5-triazinyl, piperazinyl, morpholinyl, tetrahydropyranyl, 1,4-dioxanyl, 1,3-dioxanyl, Dioxolanyl, dioxolyl, tetrahydrofuranyl, dihydrofuranyl, oxetanyl, thietanyl, oxide thietanyl, dioxide thietanyl, oxiranyl, azetidinyl, oxoazetidinyl, oxazepanyl, oxadinanyl, azepanyl, oxopyrrolidinyl, dioxopyrrolidinyl, A mono- or poly-substituted heterocycle from the group of oxomorpholinyl, oxopiperidinyl, oxopiperazinyl and oxotetrahydrofuranyl,
Here, the substituent is amino, C ₁ -C ₆ -alkyl, C, which may be mono-substituted from halogen, nitro, cyano or hydroxyl, or may be poly-substituted with the same or different ones. ₁ -C ₆ - _alkoxy, C 1 -C ₆ - alkoxy _-C 1 -C ₆ - _alkyl, C 1 -C ₆ - _{alkylcarbonyl,} C 2 -C ₆ - _alkenyl, C 2 -C ₆ - alkynyl, _{C 3} -C ₆ - cycloalkyl, aryl, _hetaryl, C 1 -C ₆ - _arylalkyl, C 1 -C ₆ - hetarylalkyl, aryloxy, _hetaryloxy, C 1 -C ₆ - _{alkylsulfinyl,} C 1 -C ₆ - _{alkylsulfonyl,} C 1 -C ₆ - _alkylthio, C 1 -C ₆ - is selected from alkoxycarbonyl and heterocycle,
Here, the substituent is independently halogen, nitro, hydroxyl, amino, cyano, C ₁ -C ₆ -alkyl, C ₁ -C ₆ -alkylcarbonyl, C ₁ -C ₆ -haloalkyl, C ₁ -C. ₆ - _alkoxy, C 1 -C ₆ - _haloalkoxy, C 3 -C ₆ - _cycloalkyl, C 3 -C ₆ - _{cycloalkylcarbonyl,} C 1 -C ₆ - _alkylthio, C 1 -C ₆ - alkylsulfinyl, C ₁ -C ₆ - _{alkylsulfonyl, (C} 1 -C ₆ - alkoxy) _carbonyl, C 2 -C ₆ - _alkenyl, C 2 -C ₆ - _alkynyl, C 1 -C ₆ - _alkylamino, C 3 -C ₆ - Cycloalkylamino, (C ₁ -C ₆ -alkyl) C ₃ -C ₆ -cycloalkylamino, di (C ₁ -C ₄ ) alkylamino and C ₁ -C ₆ - it can be selected from alkyl aminocarbonyl,
Q ¹ to Q ³ are each independently a carbon atom substituted with hydrogen or R ¹ ;
Q ⁴ is a carbon atom substituted by hydrogen or R ⁶ or bonded to V (where V is other than R ⁴ );
Q ⁵ to Q ⁸ are each independently a carbon atom substituted by hydrogen, R ⁶ or A—Y, and exactly one of Q ⁵ , Q ⁶ , Q ⁷ , Q ⁸ is replaced by A—Y A compound of general formula (I) according to claim 1 or a diastereomer, enantiomer, E / Z isomer or salt of said compound. R ¹ is hydrogen, nitro, cyano, fluorine, chlorine, bromine, iodine, methyl, ethyl, n- or i-propyl, fluoromethyl, chloromethyl, trichloromethyl, difluoromethyl, dichlorofluoromethyl, chlorodifluoromethyl, tri Fluoromethyl, fluoroethyl, chloroethyl, difluoroethyl, dichloroethyl, trifluoroethyl, chlorofluoroethyl, chlorodifluoroethyl, dichlorofluoroethyl, tetrafluoroethyl, pentafluoroethyl, chlorotetrafluoroethyl, trichloroethyl, heptafluoro-n -Propyl, heptafluoroisopropyl, methoxy, ethoxy, n- or i-propoxy, fluoromethoxy, difluoromethoxy, trifluoromethoxy, methylthio, ethylthio, di Fluoromethylthio, trifluoromethylthio, chlorodifluoromethylthio, methylsulfinyl, trifluoromethylsulfinyl, trifluoromethylsulfonyl, methylsulfonyl, ethylsulfonyl, acetyl, propionyl, methoxycarbonyl, ethoxycarbonyl, methylaminocarbonyl, dimethylaminocarbonyl or ethylamino Carbonyl,
n is 1, 2 or 3,
R ² is hydrogen;
R ³ is hydrogen, methyl, ethyl, 2-ethynyl, 2-propenyl, methoxymethyl, ethoxymethyl, methylcarbonyl, ethylcarbonyl, methoxycarbonyl, ethoxycarbonyl, n-propoxycarbonyl, i-propoxycarbonyl, n-butoxycarbonyl , T-butoxycarbonyl or phenoxycarbonyl,
V is R ⁴ , or is —O— or —N (R ⁸ ) —, and is bonded to Q ⁴ through a single bond, where R ⁴ is hydrogen, and R ⁸ is hydrogen, methyl, ethyl, methylcarbonyl, ethylcarbonyl, methoxymethyl, ethoxymethyl, cyanomethyl, cyanoeth-2-yl, propyl, phenylmethyl, prop-2-en-1-yl, prop-2-yne -1-yl, benzyloxy, methoxycarbonyl, ethoxycarbonyl, methoxycarbonylmethyl, ethoxycarbonylmethyl, methoxycarbonyleth-2-yl, ethoxycarbonyleth-2-yl, amidomethyl, amidoethyl or amidoprop-3-yl;
R ⁵ is hydrogen;
R ⁶ is hydrogen, nitro, cyano, fluorine, chlorine, bromine, iodine, methyl, ethyl, n- or i-propyl, n-, i-, s- or t-butyl, ethynyl, propynyl, fluoromethyl, chloro Methyl, trichloromethyl, difluoromethyl, dichlorofluoromethyl, chlorodifluoromethyl, trifluoromethyl, fluoroethyl, chloroethyl, difluoroethyl, dichloroethyl, trifluoroethyl, chlorofluoroethyl, chlorodifluoroethyl, fluorodichloroethyl, tetrafluoroethyl , Pentafluoroethyl, chlorotetrafluoroethyl, trichloroethyl, heptafluoro-n-propyl, heptafluoroisopropyl, methoxy, ethoxy, n- or i-propoxy, fluoromethoxy, difluorome Toxyl, trifluoromethoxy, methylthio, ethylthio, difluoromethylthio, trifluoromethylthio, chlorodifluoromethylthio, methylsulfinyl, trifluoromethylsulfinyl, trifluoromethylsulfonyl, methylsulfonyl, ethylsulfonyl, acetyl, propionyl, methoxycarbonyl, ethoxycarbonyl, Methylaminocarbonyl, ethylaminocarbonyl or dimethylaminocarbonyl,
m is 0, 1 or 2;
X is trifluoromethyl, difluoromethyl, fluoromethyl, chlorodifluoromethyl, dichlorofluoromethyl, 2-fluoroethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, 1,2,2,2 -Tetrafluoroethyl, 1-chloro-1,2,2,2-tetrafluoroethyl, 2-chloro-2,2-difluoroethyl, 1,1-difluoroethyl, pentafluoroethyl, heptafluoro-n-propyl or Nonafluoro-n-butyl,
W is O,
1,2-Y may be combined to be cyano or mono- or poly-substituted 1,2,4-oxadiazol-3-yl, 1H-imidazol-1-yl, 1H-pyrazole -1-yl, 1H-1,2,4-triazol-1-yl, 1H-1,2,3-triazol-1-yl, 1H-1,3,4-triazol-1-yl, 1H-1 , 2,3,4-tetrazol-1-yl or 2H-1,2,3,4-tetrazol-1-yl from the group of
Here, the substituent is fluorine, chlorine, cyano, hydroxyl, amino, methyl, ethyl, difluoromethyl, trifluoromethyl, pentafluoroethyl, n- or i-propyl, cyclopropyl, methoxy, ethoxy, n- or i-propoxy, fluoromethoxy, difluoromethoxy, trifluoromethoxy, fluoroethoxy, difluoroethoxy, trifluoroethoxy, methylthio, methylsulfinyl, methylsulfonyl, ethylthio, ethylsulfinyl, ethylsulfonyl, methoxycarbonyl, ethoxycarbonyl, methylaminocarbonyl or Selected from dimethylaminocarbonyl,
Or A is a moiety —NR ¹³ C (═O) —, —C (R ¹¹ ) (R ¹² ) NR ¹³ C (═O) —, —C (R ¹¹ ) (R ¹² ) NR ¹³ S (═O ) ₂ −, —C (═O) NR ¹³ —, —C (═O) N (R ¹³ ) —O—, —C (═O) NR ¹³ CH ₂ —, —S (═O) _p —, —S (═O) ₂ NR ¹³ —, —C (═O) O—, —C (═O) NR ¹³ CH ₂ C (═O) NR ^{1
4 -, - C (R 11} ) (R 12) NR 13 -, C (R 11) (U) NR 13 C (= O) - and ^{-C (= O) NR 13 NR} 14 - two selected from The chemical part of the valence, where
The first (left) linking moiety in the divalent chemical moiety is in each case linked to the ring at one of positions Q ⁴ to Q ⁸ and the second (right) linking moiety is linked to Y in each case. And
U is ethyl or n-propyl and forms a 5- or 6-membered ring with the carbon atom adjacent to the linkage site of A to the ring at positions Q ⁴ to Q ⁸ ;
p is 0, 1, 2 and where R ¹¹ and R ¹² are each hydrogen or methyl;
R ¹³ and R ¹⁴ are each hydrogen, methyl, ethyl, cyclopropyl, cyanoethyl, 2-ethynyl, 2-propenyl, methoxymethyl, ethoxymethyl, methylcarbonyl, ethylcarbonyl, n-propylcarbonyl, i-propylcarbonyl, n -Butylcarbonyl, t-butylcarbonyl, methoxycarbonyl, ethoxycarbonyl, n-propoxycarbonyl, i-propoxycarbonyl, n-butoxycarbonyl, t-butoxycarbonyl or phenoxycarbonyl,
Y may be hydrogen or mono-substituted, or may be poly-substituted with the same or different, methyl, ethyl, n- or i-propyl, n-, i-, s- or t-butyl N-, i-, s-, t- or neo-pentyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, ethenyl, propenyl, butenyl, pentenyl, ethynyl, propynyl, butynyl or pentynyl,
Wherein no more than 5 substituents may be selected from fluorine and chlorine and no more than 2 substituents may be bromine, cyano, nitro, hydroxyl, amino, methylamino, dimethylamino, cyclopropyl, trifluoromethyl, Methoxy, ethoxy, n- or i-propoxy, fluoromethoxy, difluoromethoxy, trifluoromethoxy, fluoroethoxy, difluoroethoxy, trifluoroethoxymethylthio, methylsulfinyl, methylsulfonyl, ethylthio, ethylsulfinyl, ethylsulfonyl, methoxycarbonyl and ethoxy May be selected from carbonyl,
One substituent may be mono- to tri-substituted phenyl, pyridin-2-yl, pyridin-3-ylpyridin-4-yl, thiazol-2-yl, thiazol-4-yl, furan-2 -Yl, pyrazol-1-yl, pyrazol-5-yl and pyrazol-3-yl, wherein the substituent is fluorine, chlorine, bromine, cyano, nitro, hydroxyl, methyl, ethyl, n- or i-propyl, amino, methylamino, dimethylamino, cyclopropyl, methoxy, ethoxy, n- or i-propoxy, fluoromethoxy, difluoromethoxy, trifluoromethoxy, fluoroethoxy, difluoroethoxy, trifluoroethoxy, methylthio Methylsulfinyl, methylsulfonyl, ethylthio, It may be selected from Chirusurufiniru or ethylsulfonyl,
Or mono to tri-substituted oxetane-3-yl, thietan-3-yl, 1-oxide thietan-3-yl, 1,1-dioxide thietan-3-yl, tetrahydrofuran-2-yl , Tetrahydrofuran-3-yl, tetrahydropyran-2-yl, tetrahydropyran-3-yl, tetrahydropyran-4-yl, 1,3-dioxan-2-yl, 1,3-dioxane-3-yl, 1, 3-dioxan-4-yl, 1,4-dioxan-2-yl, morpholin-1-yl, phenyl, pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, pyrimidin-2-yl, Pyrimidin-4-yl, pyrimidin-5-yl, pyridazin-3-yl, pyrazin-2-yl, furan-2-yl, furan-3-yl, thiophene -2-yl, thiophen-3-yl, pyrrol-2-yl, thiazol-2-yl, thiazol-4-yl, thiazol-5-yl, 1,2,4-thiadiazol-5-yl, oxazole-2 -Yl, oxazol-4-yl, oxazol-5-yl, isoxazol-3-yl, isoxazol-4-yl, isoxazol-5-yl, 1,2,3-oxadiazol-4-yl, 1,3,4-oxadiazol-2-yl, 1H-imidazol-2-yl, 1H-imidazol-4-yl, 1H-imidazol-5-yl, 1H-pyrazol-3-yl, 1H-pyrazol- 4-yl, 1H-pyrazol-5-yl, 1H-1,2,4-triazol-3-yl, 1H-1,2,4-triazol-5-yl, 1H-1,2, -Triazol-4-yl, 1H-1,2,3-triazol-5-yl, 2H-1,2,3-triazol-2-yl, 2H-1,2,3-triazol-4-yl, 1H -1,3,4-triazol-2-yl, 1H-1,2,3,4-tetrazol-5-yl, 2-oxopiperidin-3-yl, 2-oxotetrahydrofuran-3-yl or 5-oxo Tetrahydrofuran-2-yl,
Here, the substituent is fluorine, chlorine, bromine, cyano, nitro, hydroxyl, amino, methyl, ethyl, difluoromethyl, trifluoromethyl, pentafluoroethyl, n- or i-propyl, cyclopropyl, methoxy, ethoxy. N- or i-propoxy, fluoromethoxy, difluoromethoxy, trifluoromethoxy, fluoroethoxy, difluoroethoxy, trifluoroethoxy, methylthio, methylsulfinyl, methylsulfonyl, ethylthio, ethylsulfinyl, ethylsulfonyl, methoxycarbonyl, ethoxycarbonyl, May be selected from methylaminocarbonyl and dimethylaminocarbonyl,
Q ¹ to Q ³ are each independently a carbon atom substituted by hydrogen or R ¹ ;
Q ⁴ is hydrogen or a carbon atom substituted by R ⁶ or bonded to V (in which case V is other than R ⁴ );
Q ⁵ to Q ⁸ are each independently a carbon atom substituted by hydrogen, R ⁶ or A—Y, and exactly one of Q ⁵ , Q ⁶ , Q ⁷ , Q ⁸ is replaced by A—Y A compound of general formula (I) according to claim 1 or a diastereomer, enantiomer, E / Z isomer or salt of said compound. The compound of general formula (I) or the diastereomer or enantiomer of the compound according to claim ⁴ , wherein V is R ⁴ , R ⁴ is hydrogen, R ⁵ is hydrogen, and W is O. E / Z isomers or salts. a) Amines of the following general formula (III):

A carboxylic acid or carbonyl halide of the following general formula (II):

(L is halogen or hydroxyl, Q ¹ to Q ⁸ , R ¹ to R ⁶ , A, X, Y, V, m, and n are as defined in any one of claims 1 to 4 To obtain a compound of the general formula (I) in which W is O,
b) Optionally, the compound of general formula (I) wherein W is O is then reacted with a sulfurizing reagent to obtain a compound of general formula (I) wherein W is S. A process for producing a compound of general formula (I). a) Amines of the following general formula (III):

The
Acrylic acid derivatives of the following general formula (V):

And acrylamide of the following general formula (VI):

Get
b) The acrylamide of the general formula (VI) is then converted to a halogen compound of the following general formula (VII) in the presence of a palladium catalyst:

To give a compound of general formula (I) (L is halogen or hydroxyl, L ¹ is chlorine, bromine, iodine or triflate, Q ¹ to Q ⁸ , R ¹ to R ⁶ , A , X, Y, m, and n are each defined as described in claim 5.), A process for producing a compound of general formula (I) according to claim 5. A compound of the following general formula (VI):

Wherein Q ¹ to Q ³ , R ¹ , R ² , R ³ , X and n are each defined as defined in claim 4, Q ¹ to Q ³ are each —CH, R ¹ , (R ² and R ³ are each H, and compounds where n is 1 are excluded.)   A method for producing an agrochemical, comprising mixing the compound of the general formula (I) according to claim 1 and / or a salt of the compound with a filler and / or a surfactant.   Use of a compound of general formula (I) and / or a salt of said compound according to claim 1 in the production of agricultural chemicals.   A pesticide comprising a compound of the general formula (I) according to claim 1 and / or a salt of the compound with a physiologically active content of 0.00000001 to 95% by weight based on the weight of the pesticide.   The agrochemical according to claim 11, further comprising another active agrochemical component.   A method for controlling animal pests, which comprises causing the compound of general formula (I) according to claim 1 and / or a salt of the compound to act on animal pests and / or their place of growth. The compound of the following general formula (II).

[Where:
L is halogen or hydroxyl;
V is —N (R ⁸ ) — and is bonded to Q ⁴ via a single bond, where R ⁸ may be mono-substituted or poly-substituted with the same or different. C ₁ -C ₆ alkyl, C ₂ -C ₆ alkenyl or C ₂ -C ₆ alkynyl, wherein the substituents are each independently selected from halogen or C ₁ -C ₆ alkoxy,
Q ⁴ is a carbon atom,
R ⁵ is hydrogen or halogen;
R ⁶ is halogen,
m is 1, 2 or 3;
A is —C (═O) NR ¹³ or —C (═O) O—, wherein R ¹³ is hydrogen, mono-substituted, or poly-substituted with the same or different. Optionally substituted C ₁ -C ₆ alkyl or C ₃ -C ₆ cycloalkyl, C ₁ -C ₆ alkylcarbonyl, C ₁ -C ₆ alkoxycarbonyl or aryloxycarbonyl, wherein the substituents are each independently Selected from halogen, cyano, nitro, hydroxyl, C ₁ -C ₆ alkyl or C ₁ -C ₆ alkoxy;
Y is hydrogen, mono-substituted, or C ₁ -C ₆ alkyl, C ₂ -C ₆ alkenyl, C ₂ -C ₆ alkynyl, C ₃ which may be the same or different and multi-substituted. -C ₆ cycloalkyl or _C 3 -C ₆ cycloalkenyl, wherein said substituents are halogen independently, _cyano, C 1 -C _{6 alkyl,} C 2 -C _{6 alkenyl,} C 2 -C ₆ is selected from alkynyl, or _C 1 -C ₆ alkoxy,
Q ⁵ to Q ⁸ are each independently a carbon atom substituted by hydrogen, R ⁶ or A—Y, and exactly one of Q ⁵ , Q ⁶ , Q ⁷ , Q ⁸ is replaced by A—Y Has been. ] R ⁵ is hydrogen;
Q ⁶ is substituted with A-Y, compounds of formula (II) according to claim 14. R ⁵ is hydrogen;
Q ⁷ is substituted with A-Y, compounds of formula (II) according to claim 14. R ⁶ is chlorine, compounds of formula (II) according to claim 14.