專利名稱：殺蟲(chóng)二酰胺類(lèi)的制作方法
技術(shù)領(lǐng)域：
本發(fā)明涉及某些二酰胺類(lèi)、它們的N-氧化物、其適用于農(nóng)業(yè)的鹽和組合物，以及它們?cè)谵r(nóng)業(yè)和非農(nóng)業(yè)環(huán)境中防治無(wú)脊椎害蟲(chóng)的使用方法。
背景技術(shù)：
無(wú)脊椎害蟲(chóng)(例如節(jié)肢動(dòng)物)的防治在實(shí)現(xiàn)高效農(nóng)業(yè)中是非常重要的。無(wú)脊椎害蟲(chóng)危害農(nóng)作物的生長(zhǎng)和貯存，會(huì)導(dǎo)致農(nóng)作物嚴(yán)重減產(chǎn)，從而增加消費(fèi)者的費(fèi)用。在森林、溫室作物、觀賞植物、苗圃作物、貯存的食品和纖維產(chǎn)品、家畜、家庭、以及公共與動(dòng)物保健中，防治無(wú)脊椎害蟲(chóng)也是重要的。雖然為此目的已可買(mǎi)到許多產(chǎn)品，但是仍然需要更有效、價(jià)廉、低毒、對(duì)環(huán)境更安全或具有不同作用方式的新化合物。
NL 9202078公開(kāi)了用作殺蟲(chóng)劑的式i的N-?；彴被郊姿嵫苌?其中，X是直接鍵；
Y是H或C1-C6烷基；Z是NH2、NH(C1-C3烷基)或N(C1-C3烷基)2；和R1-R9獨(dú)立地是H、鹵素、C1-C6烷基、苯基、羥基、C1-C6烷氧基或C1-C7酰氧基。
美國(guó)專利US 3,907,892公開(kāi)了某些N-氟烷?；?鄰-苯二胺類(lèi)作為殺蟲(chóng)劑。
發(fā)明概述本發(fā)明涉及式I的化合物(包括所有幾何異構(gòu)體和立體異構(gòu)體)、及其N(xiāo)-氧化物和其適用于農(nóng)業(yè)的鹽 其中J是苯環(huán)、萘環(huán)系、5-或6-元雜芳環(huán)或者芳族8-、9-或10-元稠合雜二環(huán)環(huán)系，其中每一環(huán)或環(huán)系任選取代有1-4個(gè)R5；K是-C(＝A)NR2-或-NR2C(＝A)-；L是-NR1C(＝B)-R3或-NR1SO2-R3；A和B獨(dú)立地是O或S；R1是H；或C1-C6烷基、C2-C6鏈烯基、C2-C6鏈炔基或C3-C6環(huán)烷基，每一個(gè)任選取代有一個(gè)或多個(gè)選自如下的取代基鹵素、CN、NO2、羥基、C1-C4烷氧基、C1-C4烷硫基、C1-C4烷基亞磺?；?、C1-C4烷基磺?；2-C4烷氧基羰基、C1-C4烷基氨基、C2-C8二烷基氨基和C3-C6環(huán)烷基氨基；或者R1是C2-C6烷基羰基、C2-C6烷氧基羰基、C2-C6烷基氨基羰基或C3-C8二烷基氨基羰基；R2是H、C1-C6烷基、C2-C6鏈烯基、C2-C6鏈炔基、C3-C6環(huán)烷基、C1-C4烷氧基、C1-C4烷基氨基、C2-C8二烷基氨基、C3-C6環(huán)烷基氨基、C2-C6烷氧基羰基或C2-C6烷基羰基；R3是C1-C6烷基、C2-C6鏈烯基、C2-C6鏈炔基或C3-C6環(huán)烷基，每一個(gè)任選取代有一個(gè)或多個(gè)選自如下的取代基鹵素、CN、NO2、羥基、C1-C4烷氧基、C1-C4鹵烷氧基、C1-C4烷硫基、C1-C4烷基亞磺?；1-C4烷基磺?；2-C6烷氧基羰基、C2-C6烷基羰基、C3-C6三烷基甲硅烷基、苯基、苯氧基和5-或6-元雜芳環(huán)，每個(gè)苯基、苯氧基和5-或6-元雜芳環(huán)任選取代有1-3個(gè)獨(dú)立地選自如下的取代基R6；C1-C4烷氧基；C1-C4烷基氨基；C2-C8二烷基氨基；C1-C4烷氧基(C1-C4烷基)氨基；C3-C6環(huán)烷基氨基；C2-C6烷氧基羰基或C2-C6烷基羰基；或者R1和R3可以與-NC(＝B)-或-NSO2-部分在一起，它們相連形成一個(gè)包括2-6個(gè)碳原子并任選還包括一個(gè)氮、硫或氧原子的環(huán)，所述環(huán)任選取代有1-4個(gè)選自如下的取代基C1-C2烷基、鹵素、CN、NO2和C1-C2烷氧基；每個(gè)R4獨(dú)立地是H、C1-C6烷基、C2-C6鏈烯基、C2-C6鏈炔基、C3-C6環(huán)烷基、C1-C6鹵烷基、C2-C6鹵鏈烯基、C2-C6鹵鏈炔基、C3-C6鹵環(huán)烷基、鹵素、CN、NO2、羥基、C1-C4烷氧基、C1-C4鹵烷氧基、C1-C4烷硫基、C1-C4烷基亞磺?；1-C4烷基磺?；1-C4鹵烷硫基、C1-C4鹵烷基亞磺酰基、C1-C4鹵烷基磺酰基、C1-C4烷基氨基、C2-C8二烷基氨基、C3-C6環(huán)烷基氨基、C3-C6三烷基甲硅烷基，或者任選取代有1-3個(gè)獨(dú)立地選自R6的取代基的苯環(huán)；每個(gè)R5獨(dú)立地是C1-C6烷基、C2-C6鏈烯基、C2-C6鏈炔基、C3-C6環(huán)烷基、C1-C6鹵烷基、C2-C6鹵鏈烯基、C2-C6鹵鏈炔基、C3-C6鹵環(huán)烷基、鹵素、CN、CO2H、CONH2、NO2、羥基、C1-C4烷氧基、C1-C4鹵烷氧基、C1-C4烷硫基、C1-C4烷基亞磺?；1-C4烷基磺?；1-C4鹵烷硫基、C1-C4鹵烷基亞磺酰基、C1-C4鹵烷基磺?；?、C1-C4烷基氨基、C2-C8二烷基氨基、C3-C6環(huán)烷基氨基、C2-C6烷基羰基、C2-C6烷氧基羰基、C2-C6烷基氨基羰基、C3-C8二烷基氨基羰基、C3-C6三烷基甲硅烷基；或者每個(gè)R5獨(dú)立地是苯基、芐基、苯甲酰基、苯氧基、5-或6-元雜芳環(huán)或者芳族8-、9-或10-元稠合雜二環(huán)環(huán)系，每個(gè)苯基、芐基、苯甲?；?、苯氧基、雜芳環(huán)和芳族稠合雜二環(huán)環(huán)系任選取代有1-3個(gè)獨(dú)立地選自R6的取代基；或者兩個(gè)R5基團(tuán)與相鄰碳原子相連時(shí)可以在一起為-OCF2O-、-CF2CF2O-或-OCF2CF2O-；每個(gè)R6獨(dú)立地是C1-C4烷基、C2-C4鏈烯基、C2-C4鏈炔基、C3-C6環(huán)烷基、C1-C4鹵烷基、C2-C4鹵鏈烯基、C2-C4鹵鏈炔基、C3-C6鹵環(huán)烷基、鹵素、CN、NO2、C1-C4烷氧基、C1-C4鹵烷氧基、C1-C4烷硫基、C1-C4烷基亞磺?；?、C1-C4烷基磺?；?、C1-C4烷基氨基、C2-C8二烷基氨基、C3-C6環(huán)烷基氨基、C3-C6(烷基)環(huán)烷基氨基、C2-C4烷基羰基、C2-C6烷氧基羰基、C2-C6烷基氨基羰基、C3-C8二烷基氨基羰基或C3-C6三烷基甲硅烷基；和n是1、2、3或4；條件是L不是-NHC(＝O)-，并且R3不是取代有一個(gè)或多個(gè)氟部分的C1-C6烷基。
本發(fā)明還提供了一種防治無(wú)脊椎害蟲(chóng)的方法，包括用生物有效量的式I的化合物、其N(xiāo)-氧化物或其適用于農(nóng)業(yè)的鹽(例如以本文所述的組合物)接觸無(wú)脊椎害蟲(chóng)或其環(huán)境。
本發(fā)明還提供了一種防治無(wú)脊椎害蟲(chóng)的組合物，包括生物有效量的式I的化合物、其N(xiāo)-氧化物或其適用于農(nóng)業(yè)的鹽；和至少一種選自表面活性劑、固體稀釋劑和液體稀釋劑的其它組分。
本發(fā)明還提供了一種組合物，包括生物有效量的式I的化合物、其N(xiāo)-氧化物或其適用于農(nóng)業(yè)的鹽；和有效量的至少一種其它生物活性化合物或試劑。
本發(fā)明還提供了式I的化合物(包括所有幾何異構(gòu)體和立體異構(gòu)體)、其N(xiāo)-氧化物或其適用于農(nóng)業(yè)的鹽，其中每個(gè)R5是R5a或R5b；J是苯環(huán)、萘環(huán)系、5-或6-元雜芳環(huán)或者芳族8-、9-或10-元稠合雜二環(huán)環(huán)系，其中每一環(huán)或環(huán)系取代有一個(gè)R5a并任選取代有1-3個(gè)R5b；K是-C(＝A)NR2-或-NR2C(＝A)-；L是-NR1C(＝B)-R3或-NR1SO2-R3；A和B獨(dú)立地是O或S；R1是H或C1-C4烷基；R2是H或C1-C4烷基；R3是任選取代有鹵素、CN、OCH3或S(O)pCH3的C1-C4烷基；R5a和R5b各自獨(dú)立地是C1-C4烷基、C1-C4鹵烷基、鹵素、CN、NO2、C1-C4烷氧基、C1-C4鹵烷氧基、C1-C4烷硫基、C1-C4烷基亞磺?；?、C1-C4烷基磺?；?、C1-C4鹵烷硫基、C1-C4鹵烷基亞磺?；?、C1-C4鹵烷基磺酰基、C2-C4烷氧基羰基或C3-C8二烷基氨基羰基；或苯基、芐基或者5-或6-元雜芳環(huán)，每個(gè)苯基、芐基和雜芳環(huán)任選取代有1-3個(gè)獨(dú)立地選自R6的取代基；R5a在與K相鄰的位置與J相連；每個(gè)R6獨(dú)立地是鹵素、CN、NO2、C1-C4烷基、C2-C4鏈烯基、C2-C4鏈炔基、C3-C6環(huán)烷基、C1-C4鹵烷基、C1-C4烷氧基或C1-C4鹵烷氧基；和p是0、1或2；條件是L不是-NHC(＝O)-和R3不是取代有一個(gè)或多個(gè)氟部分的C1-C6烷基。
發(fā)明詳述在上面的陳述中，術(shù)語(yǔ)“烷基”既可以單獨(dú)使用，也可以在組合詞中使用，如“烷硫基”或“鹵烷基”中使用，它包括直鏈或支鏈烷基，如甲基、乙基、正丙基、異丙基、或者不同的丁基、戊基或己基異構(gòu)體?！版溝┗卑ㄖ辨溁蛑ф滄溝┗?-丙烯基、2-丙烯基、以及不同的丁烯基、戊烯基和己烯基異構(gòu)體。“鏈烯基”也包括多烯，如1，2-丙二烯基和2，4-己二烯基?！版溔不卑ㄖ辨溁蛑ф溔不?，如1-丙炔基、2-丙炔基以及不同的丁炔基、戊炔基和己炔基異構(gòu)體?！版溔不币部梢园ê卸鄠€(gè)三鍵的基團(tuán)，如2，5-己二炔基。“烷氧基”包括，例如甲氧基、乙氧基、正丙氧基、異丙氧基以及不同的丁氧基、戊氧基和己氧基異構(gòu)體。“烷氧基烷基”是指在烷基上取代有烷氧基?！巴檠趸榛钡膶?shí)例包括CH3OCH2、CH3OCH2CH2、CH3CH2OCH2、CH3CH2CH2CH2OCH2和CH3CH2OCH2CH2?！巴榱蚧卑ㄖф溁蛑辨溚榱蚧?，例如甲硫基、乙硫基以及不同的丙硫基、丁硫基、戊硫基和己硫基異構(gòu)體?！碍h(huán)烷基”包括，例如，環(huán)丙基、環(huán)丁基、環(huán)戊基和環(huán)己基。
術(shù)語(yǔ)“雜環(huán)環(huán)”或“雜環(huán)環(huán)系”是指是指這樣一種環(huán)或環(huán)系，其中至少一個(gè)環(huán)原子不是碳并且包括1-4個(gè)獨(dú)立地選自氮、氧和硫的雜原子，條件是每個(gè)雜環(huán)環(huán)含有不超過(guò)4個(gè)氮、不超過(guò)2個(gè)氧和不超過(guò)2個(gè)硫。所述雜環(huán)環(huán)可以通過(guò)任何可以利用的碳或氮將所述碳或氮上的氫替換相連。術(shù)語(yǔ)“芳環(huán)系”是指完全不飽和碳環(huán)和雜環(huán)，其中所述多環(huán)系是芳族的(其中芳族是指該環(huán)系滿足Hückel規(guī)則)。術(shù)語(yǔ)“雜芳環(huán)”是指完全芳族的環(huán)，其中至少一個(gè)環(huán)原子不是碳并且包括1-4個(gè)獨(dú)立地選自氮、氧和硫的雜原子，條件是每個(gè)雜環(huán)環(huán)含有不超過(guò)4個(gè)氮、不超過(guò)2個(gè)氧和不超過(guò)2個(gè)硫(其中芳族是指滿足Hückel規(guī)則)。所述雜環(huán)環(huán)可以通過(guò)任何可以利用的碳或氮將所述碳或氮上的氫替換相連。術(shù)語(yǔ)“芳族雜環(huán)環(huán)系”包括完全芳族的雜環(huán)，其中多環(huán)系中至少一個(gè)環(huán)是芳族的(其中芳族是指滿足Hückel規(guī)則)。術(shù)語(yǔ)“稠合的雜二環(huán)環(huán)系”包括由兩個(gè)稠合環(huán)組成的環(huán)系，其中至少一個(gè)環(huán)原子不是碳并且可以是如上面定義的芳族或非芳族的。
術(shù)語(yǔ)“鹵素”，可以是單獨(dú)的或在組合詞如“鹵烷基”中，包括氟、氯、溴或碘。而且，在組合詞如“鹵烷基”中使用時(shí)，所述烷基可以用鹵原子部分或完全地取代，所述鹵原子可以相同或不同。“鹵烷基”的實(shí)例包括F3C、ClCH2、CF3CH2和CF3CCl2。術(shù)語(yǔ)“鹵鏈烯基”、“鹵鏈炔基”、“鹵烷氧基”等，定義與術(shù)語(yǔ)“鹵烷基”類(lèi)似?！胞u鏈烯基”的實(shí)例包括(Cl)2C＝CHCH2和CF3CH2CH＝CHCH2?！胞u鏈炔基”的實(shí)例包括HC≡CCHCl、CF3C≡C、CCl3C≡C和FCH2C≡CCH2?！胞u烷氧基”的實(shí)例包括CF3O、CCl3CH2O、HCF2CH2CH2O和CF3CH2O。
取代基中的碳原子總數(shù)通過(guò)“Ci-Cj”前綴來(lái)表示，其中i和j是1-8的數(shù)字。例如，C1-C3烷基磺?；硎炯谆酋；帘酋；?；C2烷氧基烷基表示CH3OCH2；C3烷氧基烷基例如表示CH3CH(OCH3)、CH3OCH2CH2或CH3CH2OCH2；C4烷氧基烷基表示總共含有4個(gè)碳原子的烷氧基取代的烷基的不同異構(gòu)體，實(shí)例包括CH3CH2CH2OCH2和CH3CH2OCH2CH2。在上述說(shuō)明中，當(dāng)式I的化合物含有一個(gè)雜環(huán)環(huán)時(shí)，所有取代基都通過(guò)取代任何可得到的碳或氮上的氫，經(jīng)所述碳或氮連接于這些環(huán)上。
當(dāng)一基團(tuán)含有一取代基(可以是氫)，例如R3，那么當(dāng)該取代基為氫時(shí)，應(yīng)認(rèn)為這相當(dāng)于所述基團(tuán)未取代。
本發(fā)明的化合物可以存在一種或多種立體異構(gòu)體。各種立體異構(gòu)體包括對(duì)映體、非對(duì)映異構(gòu)體、阻轉(zhuǎn)異構(gòu)體和幾何異構(gòu)體。本領(lǐng)域技術(shù)人員懂得，當(dāng)一種立體異構(gòu)體相對(duì)于其它異構(gòu)體含量更多或當(dāng)從其它異構(gòu)體分離出來(lái)的時(shí)候，該立體異構(gòu)體可以顯示更高的活性和/或可以呈現(xiàn)有益的效果。另外，本領(lǐng)域技術(shù)人員也知道如何分離、富集和/或選擇性地制備所述的立體異構(gòu)體。因此，本發(fā)明的這些化合物可以立體異構(gòu)體的混合物、單個(gè)立體異構(gòu)體、或以一種光學(xué)活性形式存在。
本發(fā)明包括選自以下的化合物式I、其N(xiāo)-氧化物及其適用于農(nóng)業(yè)的鹽。本領(lǐng)域技術(shù)人員懂得，不是所有含氮雜環(huán)都可以形成N-氧化物，因?yàn)橐趸裳趸铮枰幸粚?duì)可以利用的孤對(duì)電子；本領(lǐng)域技術(shù)人員知道，哪些含氮雜環(huán)可以形成N-氧化物。本領(lǐng)域技術(shù)人員也知道，叔胺可以形成N-氧化物。制備雜環(huán)和叔胺的N-氧化物的合成方法是本領(lǐng)域技術(shù)人員熟知的，包括用過(guò)氧酸(如過(guò)氧乙酸和間氯過(guò)苯甲酸(MCPBA)、過(guò)氧化氫、烷基氫過(guò)氧化物如叔丁基氫過(guò)氧化物、過(guò)硼酸鈉)和二環(huán)氧乙烷類(lèi)(如二甲基二環(huán)氧乙烷)氧化雜環(huán)和叔胺。這些制備N(xiāo)-氧化物的方法已在文獻(xiàn)中深入描述或綜述，參見(jiàn)文獻(xiàn)舉例如下T.L.Gilchrist的“Comprehensive Organic Synthesis”，第7卷，第748-750頁(yè)，S.V.Ley編輯，Pergamon出版社；M.Tisler和B.Stanovnik的“Comprehensive Heterocyclic Chemistry”，第3卷，第18-19頁(yè)，A.J.Boulton和A.McKillop編輯，Pergamon出版社；M.R.Grimmett和B.R.T.Keene的“Advances in HeterocyclicChemistry”，第43卷，第139-151頁(yè)，A.R.Katritzky編輯，Academic出版社；M.Tisler和B.Stanovnik的“Advances in HeterocyclicChemistry”，第9卷，第285-291頁(yè)，A.R.Katritzky和A.J.Boulton編輯，Academic出版社；和G.W.H.Cheeseman和E.S.G.Werstiuk的“Advances in Heterocyclic Chemistry”，第22卷，第390-392頁(yè)，A.R.Katritzky和A.J.Boulton編輯，Academic出版社。
本發(fā)明化合物的鹽包括與無(wú)機(jī)或有機(jī)酸的酸加成鹽，所述酸例如有氫溴酸、鹽酸、硝酸、磷酸、硫酸、醋酸、丁酸、富馬酸、乳酸、馬來(lái)酸、丙二酸、草酸、丙酸、水楊酸、酒石酸、4-甲苯磺酸和戊酸。
為了獲得更高的活性和/或容易合成，優(yōu)選的方法是優(yōu)選1.包括式I的化合物的方法，其中K是-C(＝A)NR2-，并且A和B都是O。
優(yōu)選2.包括式I的化合物的方法，其中K是NR2C(＝A)-，并且A和B都是O。
優(yōu)選3.優(yōu)選1或優(yōu)選2的方法，其中J是苯環(huán)或者5-或6-元雜芳環(huán)，該雜芳環(huán)選自基團(tuán)J-1、J-2、J-3和J-4，每個(gè)J環(huán)任選取代有1-3個(gè)R5 Q是O、S或NR5c；W、X、Y和Z獨(dú)立地是N或CR5c，條件是在J-3和J-4中W、X、Y或Z中至少一個(gè)是N；R1和R2各自獨(dú)立地是H、C1-C4烷基、C2-C4鏈烯基、C2-C4鏈炔基、C3-C6環(huán)烷基、C2-C6烷基羰基或C2-C6烷氧基羰基；R3是C1-C6烷基、C2-C6鏈烯基、C2-C6鏈炔基或C3-C6環(huán)烷基，它們各自任選取代有一個(gè)或多個(gè)選自如下的取代基鹵素、CN、C1-C2烷氧基、C1-C2烷硫基、C1-C2烷基亞磺?；虲1-C2烷基磺?；?；每個(gè)R4獨(dú)立地是C1-C4烷基、C1-C4鹵烷基、鹵素、CN、NO2、C1-C4烷氧基、C1-C4鹵烷氧基、C1-C4烷硫基、C1-C4烷基亞磺?；?、C1-C4烷基磺?；?、C1-C4鹵烷硫基、C1-C4鹵烷基亞磺?；駽1-C4鹵烷基磺?；?；每個(gè)R5獨(dú)立地是C1-C4烷基、C1-C4鹵烷基、鹵素、CN、NO2、C1-C4烷氧基、C1-C4鹵烷氧基、C1-C4烷硫基、C1-C4烷基亞磺?；?、C1-C4烷基磺酰基、C1-C4鹵烷硫基、C1-C4鹵烷基亞磺?；?、C1-C4鹵烷基磺?；2-C4烷氧基羰基或C3-C8二烷基氨基羰基；或每個(gè)R5獨(dú)立地是苯基、芐基或者5-或6-元雜芳環(huán)，每個(gè)環(huán)任選取代有1-3個(gè)獨(dú)立地選自R6的取代基；或者兩個(gè)R5基團(tuán)與相鄰碳原子相連時(shí)可以在一起為-OCF2O-、-CF2CF2O-或-OCF2CF2O-；R5c是H或R5；每個(gè)R6獨(dú)立地是C1-C4烷基、C2-C4鏈烯基、C2-C4鏈炔基、C3-C6環(huán)烷基、C1-C4鹵烷基、C2-C4鹵鏈烯基、C2-C4鹵鏈炔基、C3-C6鹵環(huán)烷基、鹵素、CN、NO2、C1-C4烷氧基、C1-C4鹵烷氧基、C1-C4烷硫基、C1-C4烷基亞磺酰基、C1-C4烷基磺?；?、C1-C4烷基氨基、C2-C8二烷基氨基、C3-C6環(huán)烷基氨基、C3-C6(烷基)環(huán)烷基氨基、C2-C4烷基羰基、C2-C6烷氧基羰基、C2-C6烷基氨基羰基、C3-C8二烷基氨基羰基或C3-C6三烷基甲硅烷基；和n是1或2。
優(yōu)選4.優(yōu)選3的方法，其中每個(gè)R5是R5a或R5b；J取代有R5a并任選取代有1-2個(gè)R5b；R1和R2各自獨(dú)立地是H或C1-C4烷基；R3是任選取代有鹵素、CN、OCH3或S(O)pCH3的C1-C4烷基；R5a基團(tuán)在與K相鄰的位置與J相連；R5a和R5b各自獨(dú)立地是C1-C4烷基、C1-C4鹵烷基、鹵素、CN、NO2、C1-C4烷氧基、C1-C4鹵烷氧基、C1-C4烷硫基、C1-C4烷基亞磺?；1-C4烷基磺?；1-C4鹵烷硫基、C1-C4鹵烷基亞磺?；?、C1-C4鹵烷基磺?；?、C2-C4烷氧基羰基或C3-C8二烷基氨基羰基；或苯基、芐基或者5-或6-元雜芳環(huán)，每個(gè)環(huán)任選取代有1-3個(gè)獨(dú)立地選自R6的取代基；每個(gè)R6獨(dú)立地是鹵素、CN、NO2、C1-C4烷基、C2-C4鏈烯基、C2-C4鏈炔基、C3-C6環(huán)烷基、C1-C4鹵烷基、C1-C4烷氧基或C1-C4鹵烷氧基；和
p是0、1或2。
優(yōu)選5.優(yōu)選4的方法，其中J是苯基、吡唑、吡咯、吡啶或嘧啶。
優(yōu)選6.優(yōu)選5的方法，其中R1和R2各自是H；一個(gè)R4選自如下基團(tuán)C1-C3烷基、CF3、OCF3、OCHF2、S(O)pCF3、S(O)pCHF2和鹵素，并且任選的第二個(gè)R4選自如下基團(tuán)鹵素、C1-C3烷基和C1-C3鹵烷基。
優(yōu)選7.優(yōu)選6的方法，其中J是J-1；Q是NR5a；X是N或CH；Y是CH；Z是CR5b；R5a是苯基或2-吡啶基環(huán)，它們?nèi)〈幸粋€(gè)或者兩個(gè)選自如下基團(tuán)的取代基鹵素、C1-C4烷基、C1-C4鹵烷基或C1-C4鹵烷氧基；和R5b是鹵素或CF3。
本發(fā)明的方法包括這樣的實(shí)施方式，它包括用生物有效量的包含式I的化合物、其N(xiāo)-氧化物或其適用于農(nóng)業(yè)的鹽以及生物有效量的至少一種防治無(wú)脊椎害蟲(chóng)的其它化合物或試劑的組合物接觸無(wú)脊椎害蟲(chóng)或其環(huán)境，以防治無(wú)脊椎害蟲(chóng)。
本發(fā)明還涉及一種防治無(wú)脊椎害蟲(chóng)的組合物，其包括生物有效量的式I的化合物、其N(xiāo)-氧化物或其適用于農(nóng)業(yè)的鹽以及表面活性劑、固體稀釋劑和液體稀釋劑中的至少一種。本發(fā)明的優(yōu)選組合物是包含上面優(yōu)選方法的化合物的那些。
本發(fā)明還涉及上面定義的一些式I的化合物，包括其所有幾何異構(gòu)體和立體異構(gòu)體、其N(xiāo)-氧化物或其適用于農(nóng)業(yè)的鹽。為了獲得更高的活性和/或容易合成，本發(fā)明的優(yōu)選化合物是優(yōu)選A.式I的化合物，其中J是苯環(huán)或者5-或6-元雜芳環(huán)，該雜芳環(huán)選自基團(tuán)J-1、J-2、J-3和J-4，每個(gè)J環(huán)取代有R5a并任選取代有1-2個(gè)R5b Q是O、S或NR5c；W、X、Y和Z獨(dú)立地是N或CR5c，條件是在J-3和J-4中W、X、Y或Z中至少一個(gè)是N；R1和R2各自獨(dú)立地是H或C1-C4烷基；R3是C1-C4烷基，它任選取代有鹵素、CN、OCH3或S(O)pCH3；每個(gè)R4獨(dú)立地是C1-C4烷基、C1-C4鹵烷基、鹵素、CN、NO2、C1-C4烷氧基、C1-C4鹵烷氧基、C1-C4烷硫基、C1-C4烷基亞磺?；1-C4烷基磺?；1-C4鹵烷硫基、C1-C4鹵烷基亞磺酰基或C1-C4鹵烷基磺?；?；R5a在與K相鄰的位置與J相連；R5a和R5b各自獨(dú)立地是C1-C4烷基、C1-C4鹵烷基、鹵素、CN、NO2、C1-C4烷氧基、C1-C4鹵烷氧基、C1-C4烷硫基、C1-C4烷基亞磺?；?、C1-C4烷基磺酰基、C1-C4鹵烷硫基、C1-C4鹵烷基亞磺?；?、C1-C4鹵烷基磺?；?、C2-C4烷氧基羰基或C3-C8二烷基氨基羰基；或苯基、芐基或者5-或6-元雜芳環(huán)，每個(gè)環(huán)任選取代有1-3個(gè)獨(dú)立地選自R6的取代基；
R5c是H或R5a；每個(gè)R6獨(dú)立地是鹵素、CN、NO2、C1-C4烷基、C2-C4鏈烯基、C2-C4鏈炔基、C3-C6環(huán)烷基、C1-C4鹵烷基、C1-C4烷氧基或C1-C4鹵烷氧基；n是1或2；和p是0、1或2。
優(yōu)選B.優(yōu)選A的化合物，其中J是苯基、吡唑、吡咯、吡啶或嘧啶。
優(yōu)選C.優(yōu)選B的化合物，其中R1和R2各自是H；一個(gè)R4選自如下基團(tuán)C1-C3烷基、CF3、OCF3、OCHF2、S(O)pCF3、S(O)pCHF2和鹵素，并且任選的第二個(gè)R4選自如下基團(tuán)鹵素、C1-C3烷基和C1-C3鹵烷基。
優(yōu)選D.優(yōu)選C的化合物，其中J是J-1；Q是NR5a；X是N或CH；Y是CH；Z是CR5b；R5a是苯基或2-吡啶基環(huán)，它們?nèi)〈幸粋€(gè)或者兩個(gè)選自如下基團(tuán)的取代基鹵素、C1-C4烷基、C1-C4鹵烷基或C1-C4鹵烷氧基；和R5b是鹵素或CF3。
如上所述，J是苯環(huán)、萘環(huán)系、5-或6-元雜芳環(huán)或者芳族8-、9-或10-元稠合雜二環(huán)環(huán)系，其中每一環(huán)或環(huán)系任選取代有1-4個(gè)R5。與這些J基團(tuán)有關(guān)的術(shù)語(yǔ)“任選取代的”是指未取代或者具有至少一個(gè)非氫取代基的基團(tuán)，所述取代基不使未取代的類(lèi)似物所具有的防止無(wú)脊椎害蟲(chóng)活性消失。任選取代有1-4個(gè)R5的苯基的實(shí)例是顯示1中如U-1所示的環(huán)，其中Rv是R5或H，r是1-4的整數(shù)。任選取代有1-4個(gè)R5的萘基的實(shí)例如顯示1中的U-85所述，其中Rv是R5或H，r是1-4的整數(shù)。任選取代有1-4個(gè)R5的5-或6-元雜芳環(huán)的實(shí)例包括顯示1中所示的U-2至U-53，其中Rv是R5或H，r是1-4的整數(shù)。注意上面的J-1至J-4也代表5-或6-元雜芳環(huán)。注意U-2至U-20是J-1的實(shí)例，U-21至U-35和U-40是J-2的實(shí)例，U-41至U-48是J-3的實(shí)例，U-49至U-53是J-4的實(shí)例。任選取代有1-4個(gè)R5的芳族的8-、9-或10-元稠合的雜二環(huán)環(huán)系的實(shí)例包括顯示1中所述的U-54至U-84，其中Rv是R5或H，r是1-4的整數(shù)。
盡管在結(jié)構(gòu)U-1至U-85顯示存在有Rv基團(tuán)，但是應(yīng)注意的是它們可以是H，這相當(dāng)于R5任選不存在。注意當(dāng)Rv是與一原子相連的H時(shí)，這與該原子未被取代相同。需要取代以填充其化合價(jià)的這些氮原子取代有H或Rv。注意一些U基團(tuán)僅可被少于4個(gè)Rv基團(tuán)取代(例如U-14、U-15、U-18至U-21和U-32至U-34僅可被一個(gè)Rv取代)。注意當(dāng)(Rv)r和U基團(tuán)之間的連接點(diǎn)描述為浮動(dòng)的時(shí)候，(Rv)r可以與U基團(tuán)上的任何可以利用的碳原子相連。注意當(dāng)U基團(tuán)上的連接點(diǎn)描述為浮動(dòng)的時(shí)候，U基團(tuán)可以通過(guò)取代氫原子與式I的剩余部分經(jīng)U基團(tuán)的任何可以利用的碳原子相連。
顯示1



如上所述，R3可以(尤其)是C1-C6烷基、C2-C6鏈烯基、C2-C6鏈炔基、C3-C6環(huán)烷基，每一個(gè)任選取代有一個(gè)或多個(gè)選自如下的取代基苯環(huán)、苯氧基或者5-或6-元雜芳環(huán)，每個(gè)環(huán)任選取代有1-3個(gè)獨(dú)立地選自R6的取代基；C1-C4烷氧基；C1-C4烷基氨基；C2-C8二烷基氨基；C1-C4烷氧基(C1-C4烷基)氨基；C3-C6環(huán)烷基氨基；C2-C6烷氧基羰基或C2-C6烷基羰基。R3的取代環(huán)的實(shí)例包括如顯示1中所述的U-1至U-53和U-86所述的環(huán)，不過(guò)這些環(huán)任選取代有1-3個(gè)獨(dú)立地選自R6(不包括RV)的取代基。
如上所述，每個(gè)R5可以獨(dú)立地(尤其)是苯基、芐基、苯甲酰基、苯氧基、5-或6-元雜芳環(huán)或者芳族8-、9-或10-元稠合雜二環(huán)環(huán)系，每個(gè)環(huán)任選取代有1-3個(gè)獨(dú)立地選自R6的取代基。這些R5基團(tuán)的實(shí)例包括如顯示1中U-1至U-88所述的環(huán)或環(huán)系，不過(guò)這些環(huán)任選取代有1-3個(gè)獨(dú)立地選自R6(不包括RV)的取代基。
式I的化合物可以用如下反應(yīng)式1-34中所述的一種或多種方法和改進(jìn)方法制備。在下式I和式2-57的化合物中，R1-R6、J、K、L和n的定義如同本發(fā)明上面的概述中的定義，式Ia-Ie、2a、5a-e、13a-e和49a-b的化合物分別是式I、2、5、13和49的化合物的不同亞類(lèi)。
式Ia的化合物可以在有酸清除劑的情況下，將式2的胺與式3的?；扰悸?lián)制得，如反應(yīng)式1所示。典型的酸清除劑包括胺堿類(lèi)，例如三乙胺、N，N-二異丙基乙胺和吡啶；其它清除劑包括氫氧化物如氫氧化鈉和氫氧化鉀以及碳酸鹽如碳酸鈉和碳酸鉀。在某些情況下，也可以采用聚合物載酸清除劑，如結(jié)合在聚合物上的N，N-二異丙基乙胺和結(jié)合在聚合物上的4-(二甲基)氨基吡啶。所述偶聯(lián)作用可以在合適的惰性溶劑如四氫呋喃、二噁烷、二乙醚或二氯甲烷中進(jìn)行以得到式Ia的酰苯胺。
反應(yīng)式1 如反應(yīng)式2所述，制備式Ia的化合物的另一方法包括在脫水劑如1，3-二環(huán)己基碳二亞胺(DCC)存在下，將式2的胺與式4的酸偶聯(lián)。這里也可以采用聚合物載試劑，例如結(jié)合在聚合物上的1，3-環(huán)己基碳二亞胺。反應(yīng)式1和2的合成方法是用于制備式I化合物的方法的代表性實(shí)例，關(guān)于這類(lèi)反應(yīng)的合成文獻(xiàn)很多。
反應(yīng)式2 本領(lǐng)域技術(shù)人員還會(huì)知道，可通過(guò)多種熟知的方法由式4的酸制成式3的酰基氯。例如，在惰性溶劑如甲苯或二氯甲烷中在有催化量的N，N-二甲基甲酰胺的情況下將羧酸4與亞硫酰氯反應(yīng)可以容易地由式4的羧酸制備式3的酰基氯。
式2a的胺通?？梢杂墒?的相應(yīng)的硝基化合物經(jīng)如反應(yīng)式3所示的硝基催化氫化反應(yīng)獲得。典型的步驟包括在存在金屬催化劑(如Pd/C或氧化鉑)的情況下并在羥基溶劑如乙醇和異丙醇中用氫還原。它們也可以在乙酸中用鋅還原制得。這些步驟充分地公開(kāi)在化學(xué)文獻(xiàn)中。在這一階段通?？梢酝ㄟ^(guò)通常優(yōu)選的將該胺還原烷基化的方法引入R1取代基，例如烷基、取代的烷基等。常用步驟是在有還原劑如氰基硼氫化鈉的情況下將苯胺2a與醛混合制得式2化合物，其中R1是烷基、鏈烯基、鏈炔基或其取代的衍生物。
反應(yīng)式3 如反應(yīng)式4所述，將式6的胺與式7的?；韧ㄟ^(guò)與反應(yīng)式1所述的類(lèi)似方法反應(yīng)可以制得式5a的硝基苯。
反應(yīng)式4 如反應(yīng)式5所述，式6的胺(其中R2不是H)可以通過(guò)將式8的伯胺經(jīng)與反應(yīng)式3中所述的類(lèi)似方法還原烷基化制得。
反應(yīng)式5 反應(yīng)式6顯示了式5b的化合物可以在有堿(如氫化鈉或正丁基鋰)的情況下在惰性溶劑如四氫呋喃或N，N-二甲基甲酰胺(DMF)中用合適的烷基化試劑烷基化，從而得到式5a的酰苯胺，其中R2不是氫。該步驟特別適用于制備R2是烷基、鏈烯基或鏈炔基的式5a化合物。
反應(yīng)式6 反應(yīng)式7概括了式5c的硫代酰苯胺的制備方法。式5a的酰苯胺(其中R2是H、烷基等)與五硫化磷或Lawesson試劑(即2，4-二(4-甲氧基苯基)-1，3-二硫代-2，4-diphosphetane-2，4-二硫化物)在合適的溶劑如吡啶中于室溫或加熱下反應(yīng)得到式5c的硫代酰苯胺。
反應(yīng)式7 此外，式Ib的硫代酰苯胺可以由式Ia的相應(yīng)的酰苯胺經(jīng)反應(yīng)式8中所述的方法制得。
反應(yīng)式8 式Ic的化合物可以在有酸清除劑的情況下，將式2的胺與式9的磺?；确磻?yīng)制得。典型的酸清除劑包括胺堿類(lèi)，例如三乙胺、N，N-二異丙基乙胺和吡啶；其它清除劑包括氫氧化物如氫氧化鈉和氫氧化鉀以及碳酸鹽如碳酸鈉和碳酸鉀。在某些情況下，也可以采用聚合物載酸清除劑，如結(jié)合在聚合物上的N，N-二異丙基乙胺和結(jié)合在聚合物上的4-(二甲基)氨基吡啶。
反應(yīng)式9
式5e的硫酰胺可以由式5d的相應(yīng)的酰胺經(jīng)與反應(yīng)式7中所述相似的方法制得。
反應(yīng)式10 式5d的酰胺(其中R2是H)可以由式10的酰基氯或者由式11的羧酸分別經(jīng)與反應(yīng)式1和2中所述相似的方法制得。
反應(yīng)式11 式5d的酰胺(其中R2不是H)可以由式5d的相應(yīng)酰胺經(jīng)與反應(yīng)式6中所述的類(lèi)似方法制得。
反應(yīng)式12 式12的胺可以由式13的羧酸(或者相應(yīng)的酰基氯衍生物)使用Curtius、Schmitt或Lossen條件制得。這些名稱反應(yīng)在文獻(xiàn)中已被充分公開(kāi)。一些代表性的反應(yīng)條件例如參見(jiàn)R.C.Larock、ComprehensiveOrganic Transformations，1989，VCH出版社，第431-2頁(yè)。
反應(yīng)式13 式12的胺也可以將式14的合適硝基化合物通過(guò)與反應(yīng)式3中所述相似的方法還原制得。
反應(yīng)式14 式13a的苯甲酸(J是任選取代的苯基)及其制備步驟在本領(lǐng)域中為公知。本發(fā)明的苯甲酸的一個(gè)特別有用的亞類(lèi)是式13a的2-甲基-4-全氟烷基苯甲酸(一個(gè)R5是例如CF3、C2F5、C3F7)。反應(yīng)式15-19概括了這些化合物的合成。式13a的苯甲酸可以由式15的芐腈通過(guò)水解制得。所用條件可以包括使用在溶劑如水、乙醇或乙二醇中的堿如堿金屬氫氧化物或醇化物(例如氫氧化鉀或氫氧化鈉)(例如J.Chem.Soc.1948，1025)。或者，可以使用酸(如硫酸或磷酸)在合適的溶劑如水中進(jìn)行水解(例如Org.Synth.1955，Coll Vol.3，557)。條件的選擇依R5對(duì)這些反應(yīng)條件的穩(wěn)定性而定；通常使用高溫獲得這種轉(zhuǎn)化。
反應(yīng)式15
式15的腈可以由式16的苯胺通過(guò)包括重氮化并用氰化銅鹽處理該中間重氮鹽的經(jīng)典步驟制得(例如J.Amer.Chem.Soc.1902，24，1035)。
反應(yīng)式16 式16的苯胺可以由式17的化合物制得。這種轉(zhuǎn)化可以通過(guò)一種公知步驟使用阮內(nèi)鎳實(shí)現(xiàn)(Org.Synth.Coll.Vol VI，581)。或者，在有氫的情況下采用適當(dāng)?shù)拇呋瘎├玮Z，也可以進(jìn)行相同的轉(zhuǎn)化。該反應(yīng)通常在102-105kPa壓力下，在適當(dāng)?shù)挠袡C(jī)溶劑如甲苯(但不限于此)中進(jìn)行。為了完成轉(zhuǎn)化，通常需要80-110℃的高溫。作為本領(lǐng)域技術(shù)人員將知道，可以對(duì)硫醚部分進(jìn)行許多化學(xué)改性，并且在需要促進(jìn)這種轉(zhuǎn)化時(shí)可以采用。
反應(yīng)式17 式17的化合物可從式18的亞氨基硫化物(iminosulfurane)制得。該轉(zhuǎn)化可以在極性溶劑(如甲醇或水)中，在非質(zhì)子溶劑(如二氯甲烷或甲苯)中在適當(dāng)?shù)膲A如三乙胺存在下(如Org.Synth.Coll.Vol.VI，581)或甲氧基鈉存在下，或在極性溶劑、極性溶劑和堿共同存在下完成。反應(yīng)進(jìn)行的溫度通常在40-110℃的范圍內(nèi)。本領(lǐng)域技術(shù)人員知道，也可以采用式18的化合物的適當(dāng)?shù)柠}，例如，但不限于鹽酸鹽、硫酸鹽或亞硫酸鹽，條件是首先用適量的堿以產(chǎn)生游離堿18。這可以作為一個(gè)獨(dú)立的步驟，或者與包括式18的化合物轉(zhuǎn)化成式17的化合物的步驟合為一步。
反應(yīng)式18 式18的化合物可以由式19的苯胺通過(guò)與二甲基硫醚和適當(dāng)?shù)穆然瘎?如(但不限于)N-氯丁二酰亞胺(如Org.Synth.Coll.Vol.VI，581)、氯或N-氯苯并三唑)反應(yīng)制得。另外，式19的苯胺可以用二甲基砜處理，后者已通過(guò)用例如乙酸酐、三氟乙酸酐、三氟甲磺酸酐、環(huán)己基碳二亞胺、三氧化硫或五氧化二磷的試劑處理“活化”。該反應(yīng)在適當(dāng)?shù)挠袡C(jī)溶劑如二氯甲烷或二甲基砜中進(jìn)行。反應(yīng)在-70℃至25℃的溫度下進(jìn)行；最佳反應(yīng)溫度取決于所用的溶劑和反應(yīng)劑。
反應(yīng)式19 式13的雜環(huán)酸(其中J是一任選取代的雜環(huán))可以通過(guò)反應(yīng)式20-25所概括的步驟制得。在以下的概要中可以找到包括噻吩、呋喃、吡啶、嘧啶、三唑、咪唑、吡唑、噻唑、噁唑、異噻唑、噻二唑、噁二唑、三嗪、吡嗪、噠嗪和異噁唑等的多種雜環(huán)酸的一般參考文獻(xiàn)與專門(mén)參考文獻(xiàn)Rodd′s Chemistry of Chemistry of Carbon Compounds，Vol.IVa-IVI.，S.Coffey編輯，Elsevier Scientific Publishing，New York，1973；Comprehensive Heterocyclic Chemistry，Vol.1-7，A.R.Katritzky和C.W.Rees編輯，Pergamon Press，NewYork，1984；ComprehensiveHeterocyclic Chemistry II，Vol.1-9，A.R.Katritzky，C.W.Rees和E.F.Scriven編輯，Pergamon Press，NewYork，1996；及其系列，TheChemistry of Heterocyclic Compounds，E.C.Taylor編輯，Wiley，NewYork。特別有用的本發(fā)明的雜環(huán)酸包括吡啶酸、嘧啶酸和吡唑酸。在反應(yīng)式20-25中詳述了合成每個(gè)代表性實(shí)例的方法。在世界專利申請(qǐng)WO 98/57397中可找到各種雜環(huán)酸及其常規(guī)的合成方法。
式13b的代表性的吡啶酸的合成描述于反應(yīng)式20。該方法包括已知的由β-酮酯和式23的4-氨基丁酮合成吡啶。取代基R5(d)和R5(e)例如包括烷基和鹵烷基。該方法的指導(dǎo)文獻(xiàn)參見(jiàn)Synthesis，1999，(7)，1216-1222和Heterocycles，1997，46，129-132。
反應(yīng)式20 式13c的代表性的嘧啶酸的合成描述于反應(yīng)式21。該方法包括已知的由式26的亞乙烯基-β-酮酯和脒合成嘧啶。取代基R5(d)和R5(e)例如包括烷基和鹵烷基。該方法的指導(dǎo)文獻(xiàn)參見(jiàn)Bull.Soc.Chim.Fr.，1987，(2)，318-324。
反應(yīng)式21 式13d的代表性的吡唑酸的合成描述于反應(yīng)式22-25。反應(yīng)式22中13d的合成包括通過(guò)式28的吡啶的烷基化引入R5(e)取代基的關(guān)鍵步驟。烷基化試劑R5(e)-Lg(其中Lg是可離去基團(tuán)，例如Cl、Br、I、磺酸根如對(duì)甲苯磺酸基或甲磺酸基或硫酸根如-OSO2R5(e))包括R5(e)基團(tuán)，如C1-C6烷基、C2-C6鏈烯基、C2-C6鏈炔基、C3-C6環(huán)烷基、C1-C6鹵烷基、C2-C6鹵鏈烯基、C2-C6鹵鏈炔基、C3-C6鹵環(huán)烷基、C2-C6烷基羰基、C2-C6烷氧基羰基、C3-C8二烷基氨基羰基、C3-C6三烷基甲硅烷基；和苯基、芐基、苯甲酰基、5-或6-元雜芳環(huán)或芳族的8-、9-或10-元稠合的雜二環(huán)環(huán)系，每個(gè)環(huán)或環(huán)系經(jīng)過(guò)任選取代。甲基的氧化產(chǎn)生吡唑甲酸。更優(yōu)選的一些R5(d)基團(tuán)包括鹵烷基。
反應(yīng)式22
一些吡唑酸可以經(jīng)式32的吡唑的金屬化和羧化作為關(guān)鍵步驟來(lái)制備(反應(yīng)式23)。R5(e)基團(tuán)以與反應(yīng)式22類(lèi)似的方法引入，即用R5(e)烷基化試劑烷基化。代表性的R5(d)基團(tuán)包括如氰基和鹵烷基。
式13d的其它吡唑可以經(jīng)過(guò)任選取代的苯肼33與丙酮酸酯34反應(yīng)產(chǎn)生吡唑酯35來(lái)制備(反應(yīng)式24)。所得的酯水解產(chǎn)生吡唑酸13d。該方法對(duì)于制備R5(e)為任選取代的苯基并且R5(d)是鹵烷基的化合物特別有用。
反應(yīng)式23
反應(yīng)式24 式13d的吡唑酸也可以通過(guò)一個(gè)適當(dāng)取代的腈亞胺與式37的取代丙炔酸酯或者式39的丙烯酸酯經(jīng)3+2環(huán)加成來(lái)制備，如反應(yīng)式25中所示。用丙烯酸酯的環(huán)加成需要把中間體吡唑啉再氧化成吡唑。酯35水解產(chǎn)生吡唑酸13d。本反應(yīng)優(yōu)選的亞胺鹵化物包括三氟甲基亞氨基氯化物(40)和亞氨基二溴化物(41)?；衔锶?0是已知的(J.Heterocycl.Chem.1985，22(2)，565-8)?；衔锶?1可由已知方法得到(Tetrahedron Letters 1999，40，2605)。這些方法對(duì)于制備R5(e)是任選取代的苯基和R5(d)是鹵烷基或溴的化合物特別有用。
反應(yīng)式25 式12a的吡唑胺可以通過(guò)任選取代的苯肼33與式42的酮腈反應(yīng)制得。該環(huán)化反應(yīng)在現(xiàn)有技術(shù)中已充分公開(kāi)。指導(dǎo)文獻(xiàn)和一些代表性反應(yīng)條件參見(jiàn)PCT公開(kāi)WO01/004115和Synthesis，1997，(3)，337-341。反應(yīng)條件也可以參見(jiàn)本發(fā)明的實(shí)施例7。
反應(yīng)式26
式Id的化合物可以用胺12處理苯并噁嗪酮43制得，如反應(yīng)式27所示。苯并噁嗪酮與胺產(chǎn)生苯甲酰亞氨酰胺(anthranilamide)的常規(guī)反應(yīng)在化學(xué)文獻(xiàn)中已充分公開(kāi)。關(guān)于苯并噁嗪酮化學(xué)的綜述參見(jiàn)Jakobsen等人，Biorganic and Medicinal Chemistry 2000，8，2095-2103以及其中引證的文獻(xiàn)。制備苯并噁嗪酮43的代表性反應(yīng)方法參見(jiàn)Journal of Heterocyclic Chemistry，2000，37(4)，725-729和Tetrahedron，1995，51(7)，1861-6。
反應(yīng)式27 式Ie的化合物可以通過(guò)反應(yīng)式28中所述的方法制得。將胺44?；?，然后將硝基還原，得到式46的胺。胺46與?；?經(jīng)反應(yīng)式1中所述的類(lèi)似方法偶聯(lián)得到式Ie的化合物。式44的化合物可以經(jīng)與反應(yīng)式3中所述的類(lèi)似方法通過(guò)還原烷基化制得。所述酰基化反應(yīng)可以通過(guò)與反應(yīng)式1和反應(yīng)式2中所述的類(lèi)似方法與?；?或酸4偶聯(lián)實(shí)現(xiàn)。
反應(yīng)式28
式13e的吡唑甲酸，其中R5是CF3，可以通過(guò)反應(yīng)式29中概括的方法制得。
反應(yīng)式29 式47的化合物(其中R8是C1-C4烷基)與合適的堿在合適的有機(jī)溶劑中反應(yīng)，在用諸如乙酸的酸中和之后，得到式48的環(huán)化產(chǎn)物。所述合適的堿例如可以是，但不限于，氫化鈉、叔丁氧基鉀、甲基亞磺酰鈉(CH3S(O)CH2，Na+)、堿金屬(如鋰、鈉或鉀)的碳酸鹽或氫氧化物、四烷基(如甲基、乙基或丁基)銨氟化物或氫氧化物、或2-叔丁基亞氨基-2-二乙基氨基-1，3-二甲基全氫化-1，3，2-diazaphosphonine。合適的有機(jī)溶劑可以是例如，但不限于，丙酮、乙腈、四氫呋喃、二氯甲烷、二甲亞砜或N，N-二甲基甲酰胺。所述環(huán)化反應(yīng)通常在約0-120℃的溫度下進(jìn)行。溶劑、堿、溫度和加入時(shí)間的影響都是相互依賴的，并且反應(yīng)條件的選擇使副產(chǎn)物的形成最小化是重要的。優(yōu)選的堿是氟化四丁基銨。
將式48的化合物脫水得到式49的化合物，接著將羧酸酯官能團(tuán)轉(zhuǎn)化成羧酸，從而得到式13e的化合物。該脫水反應(yīng)受到用催化量的合適酸處理的影響。該催化酸可以是例如，但不限于，硫酸。該反應(yīng)通常使用有機(jī)溶劑進(jìn)行。本領(lǐng)域技術(shù)人員應(yīng)了解，脫水反應(yīng)可以在各種溶劑中于通常在約0-200℃，更優(yōu)選在約0-100℃的溫度范圍內(nèi)進(jìn)行。就反應(yīng)式9的方法中的脫水反應(yīng)而言，優(yōu)選溶劑包括乙酸，溫度為約65℃。通過(guò)許多方法可以將羧酸酯化合物轉(zhuǎn)化成羧酸化合物，這些方法包括在無(wú)水條件下親核裂解或者包括使用酸或堿的水解法(參見(jiàn)T.W.Greene和P.G.M.Wuts，Protective Groups in OrganicSynthesis，第2版，John Wiley & Sons，Inc.，New York，1991，第224-269頁(yè)的方法綜述)。就反應(yīng)式9的方法而言，優(yōu)選堿催化水解的方法。合適的堿包括堿金屬(如鋰、鈉或鉀)氫氧化物。例如，所述酯可以溶解在水和醇如乙醇的混合物中。用氫氧化鈉或氫氧化鉀處理之后，將該酯皂化得到羧酸的鈉或鉀鹽。用強(qiáng)酸，如鹽酸或硫酸酸化，得到式13e的羧酸。該羧酸可以通過(guò)本領(lǐng)域技術(shù)人員已知的方法分離，這些方法包括結(jié)晶、萃取和蒸餾。
式47的化合物可以通過(guò)反應(yīng)式30中概括的方法制備。
反應(yīng)式30 其中，R5為CF3，R8為C1-C4的烷基。
在溶劑如水、甲醇或乙酸中用式51的酮處理式50的肼化合物得到式52的腙。本領(lǐng)域技術(shù)人員將意識(shí)到，該反應(yīng)可能需要任選的酸催化，并且可能還需要高溫，這取決于式52的腙的分子取代形式。式52的腙與式53的化合物在合適的有機(jī)溶劑(例如，但不限于，二氯甲烷或四氫呋喃)中在有酸清除劑(如三乙胺)的情況下反應(yīng)得到式47的化合物。該反應(yīng)通常在約0-100℃的溫度下進(jìn)行。反應(yīng)式30的方法的進(jìn)一步試驗(yàn)細(xì)節(jié)描述在實(shí)施例8。式50的肼化合物可以通過(guò)標(biāo)準(zhǔn)方法制得，例如通過(guò)將相應(yīng)的2-鹵代吡啶與肼接觸。
作為反應(yīng)式29中所述方法的替代，式13e的吡唑甲酸(其中R5是Cl或Br)也可以通過(guò)反應(yīng)式31中概括的方法制得。
反應(yīng)式31 其中R8是C1-C4烷基。
任選在有酸的情況下將式54的化合物氧化得到式49的化合物，接著將羧酸酯官能團(tuán)轉(zhuǎn)化成羧酸，從而得到式13e的化合物。氧化劑可以是過(guò)氧化氫、有機(jī)過(guò)氧化物、過(guò)硫酸鉀、過(guò)硫酸鈉、過(guò)硫酸銨、一過(guò)硫酸鉀(例如，Oxone_)或高錳酸鉀。為了獲得完全轉(zhuǎn)化，應(yīng)使用至少1當(dāng)量的氧化劑(相對(duì)式54的化合物)，優(yōu)選約1-2當(dāng)量。這種氧化反應(yīng)通常是在有一溶劑的情況下進(jìn)行的。該溶劑可以是醚，例如四氫呋喃、對(duì)二噁烷等；有機(jī)酯，例如乙酸乙酯、碳酸二甲酯等；或者一極性質(zhì)子惰性有機(jī)溶劑，例如N，N-二甲基甲酰胺、乙腈等。適用于該氧化步驟的酸包括無(wú)機(jī)酸，例如硫酸、磷酸等；和有機(jī)酸，例如乙酸、苯甲酸等。該酸(當(dāng)使用時(shí))應(yīng)以相對(duì)式54的化合物大于0.1當(dāng)量使用。為了獲得完全轉(zhuǎn)化，可以使用1-5當(dāng)量的酸。優(yōu)選的氧化劑是過(guò)硫酸鉀，并且該氧化反應(yīng)優(yōu)選在有硫酸的情況下進(jìn)行。該反應(yīng)可以通過(guò)將式54的化合物混入所需溶劑和(如果使用的話)酸中進(jìn)行。然后以方便的速度加入氧化劑。反應(yīng)溫度通常在低至約0℃到高至溶劑沸點(diǎn)的范圍內(nèi)變化，以便獲得完成該反應(yīng)的合理反應(yīng)時(shí)間，優(yōu)選小于8小時(shí)。所需產(chǎn)物，式49的化合物，可以通過(guò)本領(lǐng)域技術(shù)人員已知的方法分離，這些方法包括結(jié)晶、萃取和蒸餾。適用于將式49的酯轉(zhuǎn)化成式13e的羧酸的方法已描述于反應(yīng)式29。
式54的化合物可以由式55的相應(yīng)化合物如反應(yīng)式32中所示制得。
反應(yīng)式32 其中R8是C1-C4烷基。
通常在有一溶劑的情況下，用鹵化試劑處理式55的化合物，得到式54的相應(yīng)鹵代化合物。可以使用的鹵化試劑包括磷酰鹵、三鹵化磷、五鹵化磷、亞硫酰氯、二鹵三烷基磷烷、二鹵二苯基磷烷、草酰氯和光氣。優(yōu)選磷酰鹵和五鹵化磷。為了獲得完全的轉(zhuǎn)化，相對(duì)式55的化合物，應(yīng)使用至少0.33當(dāng)量的磷酰鹵，優(yōu)選約0.33-1.2當(dāng)量。為了獲得完全的轉(zhuǎn)化，相對(duì)式55的化合物，應(yīng)使用至少0.20當(dāng)量的五鹵化磷，優(yōu)選約0.20-1.0當(dāng)量。就該反應(yīng)而言，優(yōu)選式55的化合物，其中R8是C1-C4烷基。該鹵化作用用的典型溶劑包括鹵化鏈烷，例如二氯甲烷、氯仿、氯丁烷等；芳族溶劑，例如苯、二甲苯、氯苯等；醚類(lèi)，例如四氫呋喃、對(duì)二噁烷、二乙醚等；和極性質(zhì)子惰性溶劑，例如乙腈、N，N-二甲基甲酰胺等。任選，可以加入一種有機(jī)堿，例如三乙胺、吡啶、N，N-二甲基苯胺等。加入一種催化劑，例如N，N-二甲基甲酰胺，也是一種選擇。優(yōu)選溶劑是乙腈且沒(méi)有堿的方法。通常，當(dāng)使用乙腈溶劑時(shí)，要求既沒(méi)有堿也沒(méi)有催化劑。優(yōu)選方法是通過(guò)將式55的化合物混入乙腈中來(lái)進(jìn)行的。然后在方便的時(shí)間內(nèi)加入該鹵化試劑，然后將該混合物保持在所需溫度，直到反應(yīng)結(jié)束。反應(yīng)溫度通常在20℃與乙腈的沸點(diǎn)之間，并且反應(yīng)時(shí)間通常小于2小時(shí)。然后將反應(yīng)物用例如碳酸氫鈉、氫氧化鈉等的無(wú)機(jī)堿或者用例如乙酸鈉的有機(jī)堿中和。目標(biāo)產(chǎn)物，式54的化合物，可以用本領(lǐng)域技術(shù)人員已知的方法(包括結(jié)晶、萃取和蒸餾)分離。
或者，式54的化合物(其中R5是Br或Cl)可以通過(guò)分別用溴化氫或氯化氫處理式54的相應(yīng)化合物制得，其中R5是不同的鹵素(例如，對(duì)于制備式54(其中R5是Br)是Cl)或者是磺酸根基團(tuán)如對(duì)甲苯磺酸基、苯磺酸根和甲磺酸基。通過(guò)該方法，將式54的原料化合物上R5鹵素或磺酸根取代基分別用來(lái)自溴化氫或氯化氫的Br或Cl替換。該反應(yīng)在合適的溶劑如二溴甲烷、二氯甲烷或乙腈中進(jìn)行。該反應(yīng)可以在大氣壓下或者在大氣壓附近或者在大于大氣壓下于壓力容器中進(jìn)行。當(dāng)式54的原料化合物中的R5是鹵素如Cl時(shí)，反應(yīng)優(yōu)選將反應(yīng)中產(chǎn)生的鹵化氫通過(guò)噴射或者其它合適的方式除去。該反應(yīng)可以在約0-100℃之間進(jìn)行，最方便地接近室溫(例如，約10-40℃)，更優(yōu)選在約20-30℃之間。加入路易斯酸催化劑(如對(duì)制備R5是Br的式54而言為三溴化鋁)可以使該反應(yīng)加速。式54的產(chǎn)物通過(guò)本領(lǐng)域技術(shù)人員已知的常規(guī)方法(包括萃取、蒸餾和結(jié)晶)分離。
式54的原料化合物(其中R5是Cl或Br)如已經(jīng)敘及的可以由式55的相應(yīng)化合物制得。式54的原料化合物(其中R5是磺酸根基團(tuán))同樣可以由式54的相應(yīng)化合物通過(guò)標(biāo)準(zhǔn)方法如用磺酰氯(例如對(duì)甲苯磺酰氯)和堿如叔胺(例如，三乙胺)在合適的溶劑如二氯甲烷中處理制得。
式13e的吡唑甲酸(其中R5是OCH2CF3)可以通過(guò)反應(yīng)式33中概括的方法制得。
反應(yīng)式33 其中R8是C1-C4烷基，并且X是離去基團(tuán)。
在該方法中，不用如反應(yīng)式32中所示的鹵化，而是將式55的化合物氧化成式49a的化合物。該氧化反應(yīng)的反應(yīng)條件已在反應(yīng)式31中將式54的化合物轉(zhuǎn)化成式49的化合物時(shí)進(jìn)行了描述。
然后在有堿的情況下將式49a的化合物與烷基化試劑CF3CH2X(56)接觸烷基化形成式49b的化合物。在該烷基化試劑56中，X是一親核反應(yīng)離去基團(tuán)，例如鹵素(例如Br、I)、OS(O)2CH3(甲磺酸基)、OS(O)2CF3、OS(O)2Ph-p-CH3(對(duì)甲苯磺酸基)等；甲磺酸基是良好的離去基團(tuán)。反應(yīng)是在有至少1當(dāng)量堿的情況下進(jìn)行的。合適的堿包括無(wú)機(jī)堿，例如堿金屬(如鋰、鈉或鉀)碳酸鹽和氫氧化物；以及有機(jī)堿，如三乙胺、二異丙基乙基胺和1，8-二氮雜二環(huán)[5.4.0]十一碳-7-烯。反應(yīng)通常是在一溶劑中進(jìn)行的，該溶劑可以包括醇類(lèi)，如甲醇和乙醇；鹵化鏈烷，如二氯甲烷；芳族溶劑，如苯、甲苯和氯苯；醚類(lèi)，如四氫呋喃；和極性質(zhì)子惰性溶劑，如乙腈、N，N-二甲基甲酰胺等。優(yōu)選將醇和極性質(zhì)子惰性溶劑與無(wú)機(jī)堿一起使用。優(yōu)選碳酸鉀作為堿，并優(yōu)選乙腈作為溶劑。反應(yīng)通常在約0-150℃之間進(jìn)行，最優(yōu)選在室溫-100℃之間。通過(guò)常規(guī)技術(shù)如萃取可以將產(chǎn)物式49b分離。然后可以通過(guò)在反應(yīng)式29中已經(jīng)描述的將式49轉(zhuǎn)化成式13e的方法將式49b的酯轉(zhuǎn)化成式13e的羧酸。
式55的化合物可以由式50的化合物如反應(yīng)式34所述制得。
反應(yīng)式34 其中R8(是C1-C4烷基。
在本方法中，在有堿和溶劑的情況下將式50的肼化合物與式57的化合物(可以使用其富馬酸酯或馬來(lái)酸酯或其混合物)接觸。堿通常是金屬醇鹽，如甲醇鈉、甲醇鉀、乙醇鈉、乙醇鉀、叔丁醇鉀、叔丁醇鋰等。相對(duì)式50的化合物，應(yīng)使用大于0.5當(dāng)量的堿，優(yōu)選0.9-1.3當(dāng)量。應(yīng)使用大于1.0當(dāng)量的式57的化合物，優(yōu)選1.0-1.3當(dāng)量?？梢允褂脴O性質(zhì)子有機(jī)溶劑和極性質(zhì)子惰性有機(jī)溶劑，如醇類(lèi)、乙腈、四氫呋喃、N，N-二甲基甲酰胺、二甲亞砜等。優(yōu)選溶劑是醇類(lèi)如甲醇和乙醇。特別優(yōu)選該醇與構(gòu)成富馬酸酯或馬來(lái)酸酯以及醇鹽堿的醇相同。反應(yīng)通常通過(guò)在該溶劑中將式18的化合物與堿混合來(lái)進(jìn)行?？梢詫⒃摶旌衔锛訜峄蚶鋮s至所需溫度，并在一段時(shí)間內(nèi)加入式57的化合物。典型的反應(yīng)溫度是0℃-所用溶劑的沸點(diǎn)。為了升高溶劑的沸點(diǎn)，反應(yīng)可以在大于大氣壓下進(jìn)行。通常優(yōu)選溫度在約30-90℃。只要熱轉(zhuǎn)移允許加入時(shí)間越快越好。典型的加入時(shí)間在1分鐘至2小時(shí)之間。最佳反應(yīng)溫度和加入時(shí)間隨式50和式57的化合物的種類(lèi)而變化。加入之后，反應(yīng)混合物可以在該反應(yīng)溫度下保持一段時(shí)間。根據(jù)該反應(yīng)溫度，所需的保持時(shí)間可以在0-2小時(shí)。通常保持時(shí)間是10-60分鐘。然后加入有機(jī)酸如乙酸等和無(wú)機(jī)酸如鹽酸、硫酸等，將該反應(yīng)物酸化。根據(jù)反應(yīng)條件和分離方式，式55的化合物上的-CO2R8官能團(tuán)可以水解成-CO2H；例如，反應(yīng)混合物中的水可以促進(jìn)這種水解。如果形成羧酸(-CO2H)，那么使用本領(lǐng)域公知的酯化法可以將其轉(zhuǎn)化回到-CO2R8，其中R8是C1-C4烷基。目標(biāo)產(chǎn)物，式55的化合物，可以通過(guò)本領(lǐng)域技術(shù)人員已知的方法，如結(jié)晶、萃取或蒸餾分離。
應(yīng)理解的是，上面所述制備式I的化合物的一些試劑和反應(yīng)條件可能與這些中間物中存在的某些官能度不相容。在這些情況下，向該合成中加入保護(hù)/去保護(hù)序列或官能團(tuán)將有助于獲得所需產(chǎn)物。使用并選擇保護(hù)基團(tuán)對(duì)化學(xué)合成領(lǐng)域的技術(shù)人員將是顯而易見(jiàn)的(例如參見(jiàn)Greene，T.W.；Wuts，P.G.M.Protective Groups in Organic Synthesis，第2版；WileyNew York，1991)。本領(lǐng)域技術(shù)人員將意識(shí)到，在一些情況下，在任何單個(gè)反應(yīng)式中加入如所述的給定試劑之后，可能需要進(jìn)行未詳細(xì)描述的其它路徑的合成步驟來(lái)完成式I的化合物的合成。本領(lǐng)域技術(shù)人員還應(yīng)意識(shí)到，在制備式I的化合物時(shí)，可能需要以不同與上述順序的順序來(lái)對(duì)上面反應(yīng)式中所述的步驟進(jìn)行組合。
本領(lǐng)域技術(shù)人員還意識(shí)到，式I的化合物和本文所述的中間物可以經(jīng)受各種親電、親核、自由基、有機(jī)金屬、氧化和還原反應(yīng)以加入取代基或者改進(jìn)現(xiàn)有的取代基。
盡管未進(jìn)一步描述，但是據(jù)信本領(lǐng)域技術(shù)人員使用前面的描述可以最充分地利用本發(fā)明。因此，以下實(shí)施例僅僅是描述性的解釋，不以任何方式限制其內(nèi)容。百分比以重量計(jì)，除了色譜溶劑混合物或者另有說(shuō)明的之外。色譜溶劑混合物的份數(shù)和百分比以體積計(jì)，除非另有說(shuō)明。1H NMR譜以ppm計(jì)從四甲硅烷降場(chǎng)報(bào)道的；s是單峰，d是雙峰，t是三重峰，q是四重峰，m是多峰，dd是雙重的雙峰，dt是雙重的三重峰，br s是寬單峰。
實(shí)施例11-(2-氯苯基)-N-[3-甲基-2-[(2-甲基-1-氧代丙基)氨基]苯基]-3(三氟甲基)-1H-吡唑-5-羧酰胺步驟A1-(2-氯苯基)-5-2-呋喃基-3-(三氟甲基)-1H-吡唑的制備向4，4，4-三氟-1-(2-糠基)-1，3-丁二酮(30.0g，146mmol)的冰醋酸(65mL)溶液中加入乙酸鈉(12.1g，148mmol)。將該混合物冷卻至約25℃，分份加入2-氯苯基肼鹽酸鹽(25.6g，145mmol)，接著適當(dāng)放熱，將該混合物加熱至60℃持續(xù)4小時(shí)，然后冷卻至25℃。用二氯甲烷(400mL)稀釋該混合物，并將有機(jī)相用水(3×250mL)、飽和碳酸鈉水溶液(2×250mL)和鹽水洗滌，然后在硫酸鎂上干燥并在減壓下蒸發(fā)，得到43.2g標(biāo)題化合物棕色油。
1H NMR(CDCl3)δ7.6(m，5H)，6.9(1H)，5.7(d，1H)。
步驟B1-(2-氯苯基)-3-(三氟甲基)-1H-吡唑-5-羧酸的制備在約0.25小時(shí)內(nèi)向含有步驟A的標(biāo)題化合物(43.2g，138mmol)的乙腈(415mL)懸浮液中加入磷酸二氫鈉一水合物(92.4g，669mmol)。在室溫下攪拌0.5小時(shí)之后，將該混合物冷卻至約5℃，并在1小時(shí)內(nèi)滴加含有亞氯酸鈉(181.7g、2.0mmol)的430mL水的溶液，同時(shí)保持反應(yīng)溫度低于10℃。[注與含水氫氧化鈉洗滌塔相連以清洗析出的黃色氣體。]加入結(jié)束之后，在5℃下將該懸浮液攪拌約1小時(shí)，在25℃下過(guò)夜，然后通過(guò)滴加濃鹽酸(150mL)酸化至pH1，然后用乙酸乙酯(1×500mL，然后2×250mL)萃取。在低于20℃的反應(yīng)溫度下將該混合的乙酸乙酯萃取物滴加到焦亞硫酸鈉水溶液(228.5g于1.05L水中)中。將該懸浮液分開(kāi)，含水層用乙酸乙酯(2×100mL)萃取。將有機(jī)層混合，在硫酸鎂上干燥并在減壓下蒸發(fā)。殘余物與己烷∶二乙醚(99∶1，100mL)一起研磨，得到32.9g標(biāo)題化合物固體。
1H NMR(DMSO-d6)δ13.9(bs，1H)，7.7(m，5H)。
步驟C1-(2-氯苯基)-N-(3-甲基-2-硝基苯基)-3-(三氟甲基)-1H-吡唑-5-羧酰胺的制備向步驟B的標(biāo)題化合物(1.2g，3.4mmol)的二氯甲烷(15mL)的混合物中加入草酰氯(0.5g，3.7mmol)，接著加入2滴N，N-二甲基甲酰胺。開(kāi)始放熱之后，在室溫、N2下將該懸浮液攪拌0.4小時(shí)，然后在減壓下蒸發(fā)，得到一油狀殘余物。將該殘余物溶解在四氫呋喃(20mL)中，加入2-甲基-6-硝基苯胺(0.5g，152.2mmol)，接著加入N，N-二異丙基乙基胺(0.7g，129.5mmol)，并在室溫、N2下將該懸浮液攪拌過(guò)夜。在減壓下將該粗混合物蒸發(fā)，在硅膠上用己烷∶乙酸乙酯(2∶1)作為洗脫劑通過(guò)閃蒸塔色譜法將該殘余物純化，得到200mg標(biāo)題化合物固體；m.p.215-220℃。
1H NMR(CDCl3)δ2.3(s，3H)，6.3-6.6(s，1H)，7.4-7.6(m，7H)，8.0(d，1H)。
步驟DN-(2-氨基-3-甲基苯基)-1-(2-氯苯基)-3-(三氟甲基)-1H-吡唑-5-羧酰胺將步驟C的標(biāo)題化合物(1.0g，2.3mmol)溶解在乙酸乙酯(50mL)中并在10％Pd/C(200mg，1.8mmol)上于Parr Shaker(45psi)中氫化3小時(shí)。接著將該反應(yīng)混合物通過(guò)Celite_硅藻助濾劑進(jìn)行過(guò)濾，并在減壓下將濾液蒸發(fā)，將所得油殘余物漿化于己烷中并過(guò)濾，得到1.0g標(biāo)題化合物灰白色固體；m.p.165-167℃。
1H NMR(CDCl3)δ2.2(s，3H)，3.6(m，2H)，6.7(m，1H)，6.9(m，1H)，7.1(m，1H)，7.2(m，1H)，7.4(m，2H)，7.5，(m，2H)，8.1(bs，1H)。
步驟E1-(2-氯苯基)-N-[3-甲基-2-[(2-甲基-1-氧代丙基)氨基]苯基]-3-(三氟甲基)-1H-吡唑-5-羧酰胺的制備向含有步驟D的標(biāo)題化合物(0.6g，1.5mmol)的四氫呋喃(20mL)懸浮液中加入異丁基氯(0.25g，2.3mmol)，接著加入I-二異丙基乙基胺(0.5g，3.9mmol)。在25℃下將該懸浮液攪拌過(guò)夜，然后用1NHCl(100mL)和乙酸乙酯(100mL)稀釋。分離有機(jī)層，用1N HCl、水、飽和碳酸氫鈉水溶液和鹽水洗滌(每一洗液為約50mL)，然后在硫酸鎂上干燥并在減壓下蒸發(fā)，得到0.6g標(biāo)題化合物(本發(fā)明的化合物)固體；m.p.240-242℃。1H NMR(CDCl3)δ1.3(d，6H)，2.5(s，3H)，2.6(m，1H)，7.0-7.6(m，9H)，9.5(s，1H)。
實(shí)施例22-甲基-6-[(2-甲基-1-氧代丙基)氨基]-N-[2-甲基-4(三氟甲基)苯基]苯甲酰胺步驟A2-甲基-N-[2-甲基-4-(三氟甲基)苯基]-6-硝基苯甲酰胺的制備將2-甲基-6-硝基苯甲酸(9.0g，49.7mmol)和亞硫酰氯(62mL)的混合物在回流下于甲苯(100mL)中加熱2.5小時(shí)，然后冷卻至25℃。在減壓下將所得懸浮液蒸發(fā)，然后與甲苯共沸。將所得殘余物溶解在四氫呋喃(10mL)中，將其滴加到含有2-氨基-5-三氟甲基甲苯(2.89g16.5mmol)和三乙胺(2.02g，20mmol)的四氫呋喃(20mL)溶液中。在25℃下將該懸浮液攪拌72小時(shí)，然后倒入水中并用乙酸乙酯(2×20mL)萃取。將該混合有機(jī)萃取物蒸發(fā)于硅膠上并在硅膠(使用梯度從100％己烷到1∶1己烷∶乙酸乙酯的洗脫劑)上通過(guò)中壓液相色譜法純化，得到1.22g標(biāo)題化合物。
1H NMR(CDCl3)δ2.4(s，3H)，2.6(s，3H)，7.5-7.7(m，5H)，8.1(m，1H)，8.2(m，1H)。
步驟B2-氨基-6-N-[2-甲基-4-(三氟甲基)苯基]苯甲酰胺的制備將步驟A的標(biāo)題化合物(2.73g，7.7mmol)溶解在乙醇(25mL)中并在Pd/C(0.2g)上使用Parr Shaker(350kPa)氫化16小時(shí)。將所得反應(yīng)懸浮液通過(guò)Colite_過(guò)濾之后，用二乙醚洗滌濾得的白色濾餅。在減壓下將這些混合的有機(jī)層蒸發(fā)，得到2.4g標(biāo)題化合物半固體。
1H NMR(CDCl3)δ2.4(m，6H)，6.8(m，3H)，7.1(m，1H)，7.4-7.7(m，4H)，8,3(m，1H)。
步驟C2-甲基-6-[(2-甲基-1-氧代丙基)氨基]-N-[2-甲基-4-三氟甲基)苯基]苯甲酰胺的制備將異丁酰氯(51.8mg，0.5mmol)加入到含有步驟B的標(biāo)題化合物(0.15g，0.5mmol)和N，N-二異丙基乙基胺(0.13g，1.0mmol)的氯仿(5mL)溶液中。在25℃下將該懸浮液攪拌過(guò)夜，然后用1N HCl稀釋。攪拌約1小時(shí)之后，將該懸浮液通過(guò)0.45微米PTFE膜過(guò)濾，并在減壓下將該濾液蒸發(fā)，得到0.08g標(biāo)題化合物(本發(fā)明的化合物)固體；m.p.＞230℃。
1H NMR(DMSO-d6)δ1.0(d，6H)，2.5(s，3H)，2.4(s，3H)，2.6(m，1H)，7.1(m，1H)，7.3(m，1H)，7.6(m，2H)，7.9(m，2H)，9.3(bs，1H)，9.9(s，1H)。
實(shí)施例32-甲基-6-[(2-甲基-1-氧代丙基)氨基]-N-[2-甲基-4-(三氟甲氧基)苯基]苯甲酰胺步驟A2-甲基-N-[2-甲基-4-(三氟甲氧基)苯基]-6-硝基苯甲酰胺的制備通過(guò)實(shí)施例2的步驟(步驟A)，將2-甲基-4-三氟甲氧基苯胺(3.15g，16.5mmol)與2-甲基-6-硝基苯甲酰氯(3.3g，16.5mmol)和三乙胺(2.02g，20mmol)于四氫呋喃(30mL)中反應(yīng)。在反應(yīng)結(jié)束之后，將反應(yīng)懸浮液倒入過(guò)量水中，并用乙酸乙酯萃取幾次。將這些混合的萃取液在硫酸鎂上干燥并在減壓下蒸發(fā)，得到一固體。將該固體通過(guò)與己烷∶二乙醚溶液一起研磨進(jìn)一步純化，得到2.73g標(biāo)題化合物。
1H NMR(CDCl3)δ2.3(s，3H)，2.6(s，3H)，7.1(m，3H)，7.5(m，1H)，7.6(m，1H)，7.9(m，1H)，8.1(m，1H)。
步驟B2-氨基-6-N-[2-甲基-4-(三氟甲氧基)-苯基]苯甲酰胺的制備通過(guò)實(shí)施例2的步驟(步驟B)，將實(shí)施例3(步驟A)的標(biāo)題化合物(2.73g，7.7mmol)氫化，得到2.4g標(biāo)題化合物半固體。
1H NMR(CDCl3)δ2.3(s，3H)，2.5(s，3H)，6.6(m，2H)，7.1(m，6H)，7.4(bs，1H)，8.0(m，1H)。
步驟C2-甲基-6-[(2-甲基-1-氧代丙基)氨基-N-[2-甲基-4-(三氟甲氧基)苯基]苯甲酰胺的制備將異丁酰氯(0.16g，1.2mmol)加入到含有步驟B的標(biāo)題化合物(0.2g，0.6mmol)和N，N-二異丙基乙基胺(0.16g，1.2mmol)的二氯甲烷(5mL)溶液中。在25℃下將該反應(yīng)攪拌過(guò)夜之后，將該懸浮液倒入水中并用乙酸乙酯萃取幾次。將這些混合的萃取物在硫酸鎂上干燥并在減壓下蒸發(fā)，得到0.13g標(biāo)題化合物(本發(fā)明的化合物)固體；m.p.＞230℃。
1H NMR(DMSO-d6)δ1.0(d，6H)，2.3(s，3H)，2.4(s，3H)，2.6(m，1H)，7.1(m，1H)，7.2-7.4(m，4H)，7.7(m，1H)，9.3(s，1H)，9.8(s，1H)。
實(shí)施例43-氯-2-[(2-甲基-1-氧代丙基)氨基]-N-[4-(三氟甲氧基)苯基]苯甲酰胺步驟A3-氯-2-硝基-N-[4-(三氟甲氧基)苯基]苯甲酰胺的制備將五氯化磷(2.14g，10.2mmol)分份加入到3-氯-2-硝基苯甲酸(2.0g，9.7mmol)的二氯甲烷(30mL)混合物中。加入結(jié)束并且氣體釋放停止之后，在室溫下將溶液攪拌0.5小時(shí)，然后在減壓下蒸發(fā)。殘余的磷酰氯在減壓下用甲苯進(jìn)一步除去，得到2.1g相應(yīng)的苯甲酰氯固體。將含有該苯甲酰氯(1.0g，4.4mmol)的二氯甲烷(10mL)溶液滴加到含有4-三氟甲氧基苯胺(0.79g，4.4mmol)和三乙胺(0.45g，4.4mmol)的二氯甲烷(3mL)溶液中。在室溫下將該懸浮液攪拌0.5小時(shí)，然后倒入過(guò)量水中并用乙酸乙酯萃取幾次。將該混合的有機(jī)萃取物用水洗滌，在硫酸鎂上干燥并在減壓下蒸發(fā)，得到一固體。將該固體用己烷∶二乙醚(1∶1)洗滌，得到1.38g標(biāo)題化合物固體；m.p.171-172℃。
1H NMR(CDCl3)δ7.2(m，3H)，7.5-7.7(m，4H)，7.8(bs，1H)。
步驟B2-氨基-3-氯-N-[4-(三氟甲氧基)苯基]苯甲酰胺的制備向硼氫化鈉(26mg，0.68mmol)的乙醇(1mL)溶液中加入含有乙酰丙酮酸銅(II)(20.0mg，0.08mmol)的2-丙醇(1mL)懸浮液，接著加入含有步驟A的標(biāo)題化合物(0.25g，0.6mmol)的2-丙醇(3mL)懸浮液，接著加入硼氫化鈉(2.0mg，78mmol)的乙醇(2mL)溶液。在25℃下將該反應(yīng)混合物攪拌7小時(shí)，然后倒入稀氯化銨水溶液中并用乙酸乙酯萃取幾次。將該混合有機(jī)萃取物在氯化鎂上干燥并在減壓下蒸發(fā)，得到0.18g標(biāo)題化合物。
1H NMR(CDCl3)δ7.3(m，5H)，7.4(m，2H)，7.6(m，2H)，7.8(bs，1H)。
步驟C3-氯-2-[(2-甲基-1-氧代丙基)氨基]-N-[4-(三氟甲氧基)苯基]苯甲酰胺的制備將異丁酰氯(57mg，0.5mmol)加入到步驟B的標(biāo)題化合物(0.18g，0.5mmol)和三乙胺(54.0mg，0.5mmol)的二氯甲烷(3mL)中的混合物中。攪拌1.5小時(shí)之后，另外加入5滴丁酰氯和5滴三乙胺。將該懸浮液攪拌2小時(shí)，然后倒入水中并用乙酸乙酯萃取幾次?；旌系妮腿∥镉盟礈?，然后在硫酸鎂上干燥并在減壓下蒸發(fā)。殘余物在硅膠上用己烷∶乙酸乙酯(2∶1)作為洗脫劑通過(guò)閃蒸塔色譜法進(jìn)一步純化，得到40.0mg標(biāo)題化合物(本發(fā)明的化合物)固體；m.p.230-233℃。
1H NMR(DMSO-d6)δ1.0(d，6H)，2.6(m，1H)，7.3-7.4(m，3H)，7.5(m，1H)，7，7(m，1H)，7.8(m，2H)，9.6(s，1H)，10.4(s，1H)。
實(shí)施例5
1-(3-氯-吡啶基)-N-[2-甲基-6-[(2-甲基-1-氧代丙基)氨基]苯基]-3-(三氟甲基)-1H-吡唑-5-羧酰胺步驟A1-(3-氯-吡啶基)-N-(2-甲基-6-硝基苯基)-3-(三氟甲基)1-1H-吡唑-5-羧酰胺的制備向0℃下1-(3-氯-2-吡啶基)-3-(三氟甲基)-1H-吡唑-5-羧酸(2.875g，9.86mmol)攪拌于二氯甲烷(30mL)中的懸浮液中加入草酰氯(5.16mL，59.2mmol)，接著滴加N，N-二甲基甲酰胺(1滴)。然后將該攪拌溶液加熱至回流并在該溫度下攪拌1小時(shí)之后，在減壓下將該溶液濃縮至干。然后將殘余物溶解在四氫呋喃(30mL)中并向該攪拌溶液中加入2-甲基-6-硝基苯胺。然后將該溶液冷卻至0℃并滴加N，N-二異丙基乙基胺(8.60mL，49.3mmol)。然后將該攪拌溶液加熱至回流，并在該溫度下攪拌42小時(shí)，然后在減壓下濃縮至干。然后將殘余物溶解在乙酸乙酯(30mL)中，并將該溶液用1N HCl(10mL)、飽和碳酸氫鈉水溶液(10mL)和鹽水(10mL)洗滌，干燥(MgSO4)并在減壓下濃縮，剩下一黃色固體。將該產(chǎn)物溶解在乙腈(6mL)中，同時(shí)攪拌，加入氨水(6mL)，并在室溫下將該溶液攪拌2小時(shí)，然后在減壓下濃縮至干。該產(chǎn)物在硅膠(3∶1 庚烷-乙酸乙酯洗脫劑)上通過(guò)閃蒸塔色譜法純化，得到標(biāo)題化合物黃色固體(1.53g)。
1H NMR(CDCl3)δ2.21(s，3H)，7.18(s，1H)，7.27(t，1H)，7.38(m，1H)，7.47(d，1H)，7.84(d，1H)，7.85(d，1H)，8.42(dd，1H)，9.16(s，1H)。
步驟BN-(2-胺-6-甲基苯基)-1-(3-氯-2-吡啶基)-3-(三氟甲基)-1H-吡唑-5-羧酰胺的制備將含有10％Pd/C(69mg)的乙醇(5mL)攪拌懸浮液的燒瓶抽真空/填充氮?dú)?x3)。然后向該懸浮液中加入1-(3-氯-吡啶基)-N-(2-甲基-6-硝基苯基)-3-(三氟甲基)-1H-吡唑-5-羧酰胺(即步驟A的產(chǎn)物)(1.38g，3.25mmol)的乙醇(9mL)溶液。然后將該燒瓶抽真空/填充氮?dú)?x3)然后抽真空/填充氫氣(x3)。在室溫下將該反應(yīng)混合物攪拌18小時(shí)，然后通過(guò)Celite_過(guò)濾并將濾床用乙醇(2×3mL)洗滌。在減壓下將濾液濃縮，得到標(biāo)題化合物灰白色固體(1.306g)。
步驟C1-(3-氯-吡啶基)-N-[2-甲基-6-[(2-甲基-1-氧代丙基)氨基]苯基]-3-(三氟甲基)-1H-吡唑-5-羧酰胺的制備向異丁酰氯(0.053mL，0.505mmol)的四氫呋喃的攪拌溶液中加入N-(2-胺-6-甲基苯基)-1-(3-氯-2-吡啶基)-3-(三氟甲基)-1H-吡唑-5-羧酰胺(即步驟B的產(chǎn)物)(0.20g，0.505mmol)。然后將該溶液冷卻至0℃，并滴加二異丙基乙基胺(0.60mL，3.59mmol)。然后在18小時(shí)內(nèi)將該攪拌溶液加熱至室溫，然后在減壓下濃縮至干。然后將殘余物溶解在乙酸乙酯(10mL)中，并將該溶液用1N HCl(10mL)、飽和碳酸氫鈉水溶液(10mL)和鹽水(10mL)洗滌，干燥(MgSO4)并在減壓下濃縮，剩下一黃色固體。該產(chǎn)物通過(guò)在熱的叔丁基甲基醚(5mL)中漿化純化，得到標(biāo)題化合物(本發(fā)明的化合物)固體(216mg)，它在215-217℃下熔融。
1H NMR(CDCl3)δ1.11(s，3H)，1.13(s，3H)，2.20(s，3H)，2.44(m，1H)，6.89(dd，1H)，7.05(s，1H)，7.07(d，1H)，7.15(s，1H)，7.35(m，1H)，7.48(s，1H)，7.81(dd，1H)，8.41(dd，1H)，9.06(s，1H)。
實(shí)施例61-(3-氯-2-吡啶基)-N-[3-甲基-2-[(2-甲基-1-氧代丙基)氨基]苯基]-3-(三氟甲基)-1H-吡唑-5-羧酰胺步驟A2-甲基-N-(2-甲基-6-硝基苯基)-丙酰胺的制備向0℃下2-甲基-6-硝基苯胺(2.5g，16.4mmol)攪拌于二氯甲烷(22.5mL)中的溶液中加入吡啶(2.5mL)，接著滴加異丁酰氯(1.72mL，16.4mmol)。在2小時(shí)內(nèi)將該溶液加熱至室溫。于室溫下再攪拌48小時(shí)之后，加入二氯甲烷(10mL)，接著加入飽和碳酸氫鈉水溶液(30mL)。然后將水相分離并用二氯甲烷(20mL)萃取。然后將有機(jī)萃取物混合，干燥(MgSO4)并在減壓下濃縮，得到標(biāo)題化合物黃色固體(3.54g)。
步驟BN-(2-氨基-6-甲基苯基)-2-甲基丙酰胺的制備將含有10％Pd/C(25mg)的乙醇(5mL)的攪拌懸浮液的燒瓶抽真空/填充氮?dú)?x3)。然后向該懸浮液中加入2-甲基-N-(2-甲基-6-硝基苯基)-丙酰胺(即步驟A的產(chǎn)物)(2.54g，11.4mmol)的乙醇(45mL)溶液。然后將該燒瓶抽真空/填充氮?dú)?x3)，然后抽真空/填充氫氣(x3)。室溫下將該反應(yīng)混合物攪拌35分鐘，然后通過(guò)Celite_過(guò)濾，并將濾床用乙醇(2×5mL)洗滌。濾液在減壓下濃縮，得到標(biāo)題化合物灰白色固體(2.19g)。
步驟C1-(3-氯-吡啶基)-N-[3-甲基-2-[(2-甲基-1-氧代丙基)氨基]苯基]-3-(三氟甲基)-1H-吡唑-5-羧酰胺的制備向0℃下1-(3-氯-2-吡啶基)-3-(三氟甲基)-1H-吡唑-5-羧酸(0.1g，0.42mmol)攪拌于二氯甲烷(4mL)中的懸浮液中加入草酰氯(0.31g，2.44mmol)，接著滴加N，N-二甲基甲酰胺(1滴)。然后將該攪拌溶液加熱至回流，并在該溫度下攪拌1小時(shí)之后，在減壓下將該溶液濃縮至干。然后將該殘余物溶解在四氫呋喃(10mL)中并向該攪拌溶液中加入N-(2-氨基-6-甲基苯基)-2-甲基丙酰胺(即步驟B的產(chǎn)物)。然后將該溶液冷卻至0℃并滴加N，N-二異丙基乙基胺(0.52mL，2.99mmol)。然后在18小時(shí)內(nèi)將該溶液加熱至室溫并在減壓下濃縮至干。然后將殘余物溶解在乙酸乙酯(10mL)中并將該溶液用1N HCl(10mL)、飽和碳酸氫鈉水溶液(10mL)和鹽水(10mL)洗滌，干燥(MgSO4)并在減壓下濃縮，得到一黃色固體。該產(chǎn)物在硅膠(1∶1庚烷-乙酸乙酯洗脫劑)上經(jīng)閃蒸塔色譜法純化，然后從乙酸乙酯中再結(jié)晶，得到標(biāo)題化合物(本發(fā)明的化合物)固體(70mg)，它在219-220℃下熔融。
1H NMR(CDCl3)δ1.27(s，3H)，1.29(s，3H)，2.29(s，3H)，2.66(m，1H)，7.02(s，1H)，7.08(s，1H)，7.10(d，1H)，7.25(s，1H)，7.33(d，1H)，7.39(m，1H)，7.84(dd，1H)，8.44(dd，1H)，9.50(s，1H)。
實(shí)施例7N-[1-(2-氯苯基)-3-(三氟甲基)-1H-吡唑-5-基]-2-甲基-6-[(2-甲基-1-氧代丙基)氨基]苯甲酰胺步驟A4，4，4-三氟-3-氧代-丁腈(或者命名為4，4，4-三氟乙酰乙腈)的制備向一500mL三頸燒瓶(配備有一個(gè)氮?dú)馄鹋萜骱蛢蓚€(gè)隔)中加入二異丙基酰胺鋰(LDA)(18.4mL，0.172mol，2M于庚烷中)，并將該反應(yīng)混合物冷卻至-72℃。在氮?dú)庀率褂锰砑勇┒返渭右宜崛柞?10.0g，0.078mol)、乙腈(6.41g，0.156mol)和THF(100mL)的0℃溶液。45分鐘之后，在1-2小時(shí)內(nèi)將該溶液加熱至室溫，用冷水(250mL)驟冷，并將有機(jī)溶劑蒸發(fā)。將含水層用二乙醚(3×250mL)洗滌，用濃HCl酸化至pH2并用二氯甲烷(3×250mL)洗滌。接著，將含水層用二乙醚(3×250mL)萃取。該二乙醚萃取物用硫酸鈉干燥并濃縮，得到標(biāo)題化合物澄清橙色油(1.38g，0.010mol，產(chǎn)率32％)。
1H NMR(CD3OD，300MHz)δ2.96(2H，s)。
步驟B1-(2-氯苯基)-3-(三氟甲基)-1H-吡唑-5-胺的制備向一Personal Chemistry(Personal Chemistry Inc.，Boston，MA，USA)10mL反應(yīng)容器中加入2-氯苯基肼(0.392g，2.19mmol)、乙醇(2.5mL)和5滴冰醋酸。加入4，4，4-三氟-3-氧代-丁腈(即步驟A的產(chǎn)物)(0.300g，2.19mmol)的乙醇(1mL)溶液，然后將該管密封，并在150℃下在微波中加熱30分鐘。將所得粗混合物濃縮并使用硅膠色譜法(乙酸乙酯/己烷，1∶4)純化，得到標(biāo)題化合物黃色固體(0.179g，0.684mmol，31％產(chǎn)率)。
1H NMR(CDCl3，300MHz)δ3.82(2H，br)，5.85(1H，s)，7.45-7.60(4H，m)。
步驟C5-甲基-2-(1-甲基乙基)-4H-3，1-苯并噁嗪-4-酮的制備向一500mL圓底燒瓶中加入2-氨基-6-甲基苯甲酸(5.00g，0.033mol)和THF(200mL)。加入異丁酰氯(7.049g，0.066mol)和三乙胺(10.04g，0.099mol)，并在室溫下將該反應(yīng)混合物攪拌過(guò)夜。除去溶劑之后，化合物通過(guò)硅膠色譜法(乙酸乙酯/己烷，1∶9)純化，得到標(biāo)題化合物白色固體(4.85g，0.024mol，72％產(chǎn)率)。
1H NMR(CDCl3、300MHz)δ1.35(6H，d)，2.78(3H，s)，2.90(1H，七重峰)，7.21(1H，d)，7.40(1H，d)，7.64(1H，t)。
步驟DN-[1-(2-氯苯基)-3-(三氟甲基)-1H-吡唑-5-基]-2-甲基-6-(2-甲基-1-氧代丙基)氨基]苯甲酰胺的制備在氮?dú)庀聦浠c(0.2g，7.9mmol，95％純度)加入到一10mL的裝有1-(2-氯苯基)-3-(三氟甲基)-1H-吡唑-5-胺(即步驟B的產(chǎn)物)(0.200g，0.76mmol)和DMF(5mL)的燒瓶中。室溫下攪拌5分鐘之后，加入5-甲基-2-(1-甲基乙基)-4H-3，1-苯并噁嗪-4-酮(即步驟C的產(chǎn)物)(0.155g，0.76mmol)。反應(yīng)通過(guò)TLC(薄層色譜法)監(jiān)控，用10滴水驟冷，并直接通過(guò)硅膠制備TLC(1∶4乙酸乙酯/己烷)純化，得到標(biāo)題化合物(本發(fā)明的化合物)白色固體(0.135g，0.29mmol，38％產(chǎn)率)。
1H NMR(CDCl3、300MHz)δ1.08(6H，d)，2.14(3H，s)，2.38(1H，m)，6.91(1H，d)，7.07(1H，s)，7.02(1H，t)，7.41-7.59(5H，m)，8.28(1H，br)，8.36(1H，br)。
下面的實(shí)施例8描述了1-(3-氯-2-吡啶基)-3-(三氟甲基)-1H-吡唑-5-羧酸的制備，它可用于通過(guò)實(shí)施例5中所述的其它步驟制備例如1-(3-氯-吡啶基)-N-[2-甲基-6-[(2-甲基-1-氧代丙基)氨基]苯基]-3-(三氟甲基)-1H-吡唑-5-羧酰胺。
實(shí)施例81-(3-氯-2-吡啶基)-3-(三氟甲基)-1H-吡唑-5-羧酸的制備步驟A3-氯-2(1H)-吡啶酮(2，2，2-三氟-1-甲基亞乙基)腙的制備在20-25℃下將1，1，1-三氟丙酮(7.80g，69.6mmol)加入到3-氯-2(1H)-吡啶酮腙(或者命名為(3-氯-吡啶-2-基)-肼)(10g，69.7mmol)中。結(jié)束加入之后，將該混合物攪拌約10分鐘。在減壓下除去該溶劑并在乙酸乙酯(100mL)和飽和碳酸鈉水溶液(100mL)之間將混合物分開(kāi)。將有機(jī)層干燥并蒸發(fā)。通過(guò)硅膠色譜(用乙酸乙酯洗脫)得到灰白色固體產(chǎn)物(11g，66％產(chǎn)率)，m.p.64-64.5℃(從乙酸乙酯/己烷中結(jié)晶之后)。
IR(nujol)ν1629，1590，1518，1403，1365，1309，1240，1196，1158，1100，1032，992，800cm-1。
1H NMR(CDCl3)δ2.12(s，3H)，6.91-6.86(m，1H)，7.64-7.61(m，1H)，8.33-8.32(m，2H)。
MS m/z 237(M+)。
步驟B(3-氯-2-吡啶基)(2，2，2-三氟-1-甲基亞乙基)酰肼乙基氫乙二酸酯(或者命名為(3-氯-2-吡啶基)(2，2，2-三氟-1-甲基亞乙基)肼)乙基氫乙二酸酯的制備0℃下將三乙胺(20.81g，0.206mol)加入到3-氯-2(1H)-吡啶酮(2，2，2-三氟-1-甲基亞乙基)腙(即步驟A的產(chǎn)物)(32.63g，0.137mol)的二氯甲烷(68mL)中。在0℃下向該混合物中滴加氯氧代乙酸乙酯(18.75g，0.137mol)的二氯甲烷(69mL)溶液。在約2小時(shí)內(nèi)將該混合物加熱至25℃。將該混合物冷卻至0℃并滴加另一份氯氧代乙酸乙酯(3.75g，27.47mmol)的二氯甲烷(14mL)。加入約1小時(shí)之后，用二氯甲烷(約450mL)稀釋該混合物，并且用水(2×150mL)洗滌該混合物。將有機(jī)層干燥并蒸發(fā)。在硅膠上進(jìn)行色譜分離(用1∶1乙酸乙酯-己烷洗脫)，得到產(chǎn)物固體(42.06g，90％產(chǎn)率)，m.p.73.0-73.5℃(從乙酸乙酯/己烷結(jié)晶之后)。
IR(nujol)ν1751，1720，1664，1572，1417，1361，1330，1202，1214，1184，1137，1110，1004，1043，1013，942，807，836cm-1。
1H NMR(DMSO-d6，115℃)1.19(t，3H)，1.72(br s，3H)，4.25(q，2H)，7.65(dd，J＝8.3，4.7Hz，1H)，8.20(dd，J＝7.6，1.5Hz，1H)，8.55(d，J＝3.6Hz，1H)。
MS m/z 337(M+)。
步驟C1-(3-氯-2-吡啶基)-4，5-二氫-5-羥基-3-(三氟甲基)-1H-吡唑-5-甲酸乙酯的制備在8小時(shí)內(nèi)將(3-氯-2-吡啶基)(2，2，2-三氟-1-甲基-亞乙基)酰肼乙基氫乙二酸酯(即步驟B的產(chǎn)物)(5g，14.8mmol)的二甲亞砜(25mL)溶液加入到氯化四丁基銨(10g)的二甲亞砜(25mL)溶液中。加入結(jié)束之后，將該混合物倒入乙酸(3.25g)的水(25mL)溶液中。在25℃下攪拌過(guò)夜之后，用甲苯萃取(4×25mL)該混合物，并將該混合的甲苯萃取物用水(50mL)洗滌，干燥并蒸發(fā)，得到一固體。在硅膠上進(jìn)行色譜分離(用1∶2乙酸乙酯-己烷洗脫)，得到產(chǎn)物固體(2.91g，50％產(chǎn)率，含有約5％的3-氯-2(1H)-吡啶酮(2，2，2-三氟-1-甲基亞乙基)腙)，m.p.78-78.5℃(從乙酸乙酯/己烷中再結(jié)晶之后)。
IR(nujol)ν3403，1726，1618，1582，1407，1320，1293，1260，1217，1187，1150，1122，1100，1067，1013，873，829cm-1。
1H NMR(CDCl3)δ1.19(s，3H)，3.20(1/2的ABZ圖譜，J＝18Hz，1H)，3.42(1/2的ABZ圖譜，J＝18Hz，1H)，4.24(q，2H)，6.94(dd，J＝7.9，4.9Hz，1H)，7.74(dd，J＝7.7，1.5Hz，1H)，8.03(dd，J＝4.7，1.5Hz，1H)。
MS m/z 319(M+)。
步驟D1-(3-氯-2-吡啶基)-3-(三氟甲基)-1H-吡唑-5-甲酸乙酯的制備將硫酸(濃，2滴)加入到1-(3-氯-2-吡啶基)-4，5-二氫-5-羥基-3-(三氟甲基)-1H-吡唑-5-甲酸乙酯(即步驟C的產(chǎn)物)(1g，2.96mmol)的乙酸(10mL)中，并將該混合物加熱至65℃持續(xù)約1小時(shí)。將該混合物冷卻至25℃并在減壓下除去大多數(shù)乙酸。將該混合物在飽和碳酸鈉水溶液(100mL)和乙酸乙酯(100mL)之間分開(kāi)。將含水層再用乙酸乙酯(100mL)。將混合的有機(jī)萃取物干燥并蒸發(fā)，得到油狀產(chǎn)物(0.66g，77％產(chǎn)率)。
IR(neat)ν3147，2986，1734，1577，1547，1466，1420，1367，1277，1236，1135，1082，1031，973，842，802cm-1。
1H NMR(CDCl3)δ1.23(t，3H)，4.25(q，2H)，7.21(s，1H)，7.48(dd，J＝8.1，4.7Hz，1H)，7.94(dd，J＝6.6，2Hz，1H)，8.53(dd，J＝4.7，1.5Hz，1H)。
MS m/z 319(M+)。
步驟E1-(3-氯-2-吡啶基)-3-(三氟甲基)-1H-吡唑-5-羧酸的制備將氫氧化鉀(0.5g，85％，2.28mmol)的水(1mL)溶液加入到1-(3-氯-2-吡啶基)-3-(三氟甲基)-1H-吡唑-5-甲酸乙酯(即步驟D的產(chǎn)物)(0.66g，2.07mmol)的乙醇(3mL)溶液中。約30分鐘之后，在減壓下除去溶劑，將該混合物溶解在水(40mL)中。將所得溶液用乙酸乙酯(20mL)洗滌。含水層用濃鹽酸酸化，并用乙酸乙酯(3×20mL)萃取。將混合的萃取物干燥并蒸發(fā)，得到固體產(chǎn)物(0.53g，93％產(chǎn)率)，m.p.178-179 C(從己烷-乙酸乙酯中結(jié)晶之后)。
IR(nujol)ν1711，1586，1565，1550，1440，1425，1292，1247，1219，1170，1135，1087，1059，1031，972，843，816cm-1。
1H NMR(DMSO-d6)δ7.61(s，1H)，7.77(m，1H)，8.30(d，1H)，8.60(s，1H)。
通過(guò)本文所述的步驟并結(jié)合本領(lǐng)域已知的方法，可以制備表1-20的下面的化合物，其中t是叔，s是仲，n是正，i是異，c是環(huán)，Me是甲基，Et是乙基，Pr是丙基，i-Pr是異丙基，Bu是丁基，Ph是苯基，OMe是甲氧基、OEt是乙氧基、SMe是甲硫基，SEt是乙硫基，CN是氰基，并且S(O)2Me是甲基磺?；?。
在如下的表1-20中propargyl為炔丙基；cyclopropyl為環(huán)丙基；pyridyl為吡啶基。
表1 R3R4aR4bRvaRvbMe 3-Me HHCF3Et 3-Me 5-Me HOCF3i-Pr3-Me HHOCF3t-Bu3-Me 5-Cl Me BrMe 3-Me HEt BrEt 3-Me HMe Cli-Pr3-Me 5-Br Et Cl
R3R4aR4bRvaRvbt-Bu 3-Me HMe Ipropargyl3-Me HMe CF3cyclopropyl 3-Me HMe OCF3i-Pr 3-Me 5-Cl Me CF3t-Bu 3-Me HMe SCF3Me 3-Me 5-CN Me SCHF2Et 3-Me HMe OCHF2i-Pr 3-Me HMe CF3t-Bu 3-Me HMe C2F5propargyl3-Me HMe C2F5cyclopropyl 3-Me HEt CF3i-Pr 3-Me Hn-Pr CF3t-Bu 3-Me 5-Br i-Pr CF3Me 3-Me HCl CF3Et 3-Me HF CF3i-Pr 3-Me HMe SMet-Bu 3-Me 5-Cl Me OMeMe 3-Me HMe OEtEt 3-Me HMe n-C3F7i-Pr 3-Me HMe i-C3F7t-Bu 3-Me 5-F Me Etpropargyl3-Me HMe OCF2CHF2Et 3-Me HMe SCF2CHF2i-Pr 3-Me HMe SO2Met-Bu 3-Me 5-Cl Me SO2CF3Me 3-Me HCF3CF3Et 3-Me HCF3Mei-Pr 3-Me HOMeCF3t-Bu 3-Me HH CF3cyclopropyl 3-Me 5-Br H OCHF2Et 3-Me HH C2F5i-Pr 3-Me 5-Me H C2F5t-Bu 3-Me HH OCF3Me 3-Me HH OCF2CHF2Et 3-Me HH SCF2CHF2i-Pr 3-Me 5-Cl H n-C3F7
R3R4aR4bRvaRvbt-Bu 3-Me H H i-C3F7propargyl 3-Me H H BrEt 3-Me H H Cli-Pr 3-Me H H SCF3t-Bu 3-Me 5-BrPhCF3cyclopropyl3-Me H PhClEt 3-Me H PhBri-Pr 3-Me H 2-pyridyl CF3t-Bu 3-Me H 2-pyridyl ClMe 3-Me H 2-ClPhCF3Et 3-Me 5-Cl2-ClPhOCF3i-Pr 3-Me H 2-ClPhBrt-Bu 3-Me H 2-ClPhClMe 3-Me H 2-ClPhSCHF2propargyl 3-Me H 2-BrPhCF3i-Pr 3-Me 5-CN2-MePhCF3t-Bu 3-Me H 2-CNPhCF3Me 3-Me H 2-FPh CF3Et 3-Me H 2，6-F2PhCF3i-Pr 3-Me 5-Br2，4-F2PhCF3t-Bu 3-Me H 2，5-F2PhCF3Me 3-Me 5-I 2-MeOPh CF3Et 3-Me H 3-Cl-2-pyridylCF3i-Pr 3-Me 5-Me3-Cl-2-pyridylOCF3t-Bu 3-Me H 3-Cl-2-pyridylBrpropargyl 3-Me H 3-Cl-2-pyridylClEt 3-Me 5-Br3-Cl-2-pyridylSCHF2i-Pr 3-Me H 3-F-2-pyridyl CF3t-Bu 3-Me H 3-CF3-2-pyridyl CF3Me 3-Me H 3-Me-2-pyridylCF3Et 3-Me H 3-Br-2-pyridylCF3i-Pr 3-Me 5-Cl3-Br-2-pyridylOCF3t-Bu 3-Me H 3-Br-2-pyridylBri-Pr 3-Me H 3-Br-2-pyridylClMe 6-Me H H CF3Et 6-Me 4-MeH OCF3
R3R4aR4bRvaRvbi-Pr 6-Me H H OCF3t-Bu 6-Me ClMeBrMe 6-Me H EtBrEt 6-Me H MeCli-Pr 6-Me 4-Br EtClt-Bu 6-Me H MeIpropargyl 6-Me H MeCF3cyclopropyl6-Me H MeOCF3i-Pr 6-Me 4-Cl MeCF3t-Bu 6-Me H MeSCF3Me 6-Me H MeSCHF2Et 6-Me H MeOCHF2i-Pr 6-Me 4-CN MeCF3t-Bu 6-Me H MeC2F5propargyl 6-Me H MeC2F5cyclopropyl6-Me H EtCF3i-Pr 6-Me H n-Pr CF3t-Bu 6-Me 4-Br i-Pr CF3Me 6-Me H ClCF3Et 6-Me H F CF3i-Pr 6-Me H MeSMet-Bu 6-Me 4-Cl MeOMeMe 6-Me H MeOEtEt 6-Me H Men-C3F7i-Pr 6-Me H Mei-C3F7t-Bu 6-Me 4-F MeEtpropargyl 6-Me H MeOCF2CHF2Et 6-Me H MeSCF2CHF2i-Pr 6-Me H MeSO2Met-Bu 6-Me 4-Cl MeSO2CF3Me 6-Me H CF3CF3Et 6-Me H CF3Mei-Pr 6-Me H OMe CF3t-Bu 6-Me H H CF3cyclopropyl6-Me 4-Br H OCHF2Et 6-Me H H C2F5
R3R4aR4bRvaRvbi-Pr 6-Me H H C2F5t-Bu 6-Me 4-MeH OCF3Me 6-Me H H OCF2CHF2Et 6-Me H H SCF2CHF2i-Pr 6-Me 4-ClH n-C3F7t-Bu 6-Me H H i-C3F7propargyl 6-Me H H BrEt 6-Me H H Cli-Pr 6-Me H H SCF3t-Bu 6-Me 4-BrPh CF3cyclopropyl6-Me H Ph ClEt 6-Me H Ph Bri-Pr 6-Me H 2-pyridyl CF3t-Bu 6-Me H 2-pyridyl ClMe 6-Me H 2-ClPh CF3Et 6-Me 4-Cl2-ClPh OCF3i-Pr 6-Me H 2-ClPh Brt-Bu 6-Me 4-CN2-ClPh ClMe 6-Me H 2-ClPh SCHF2propargyl 6-Me H 2-BrPh CF3i-Pr 6-Me H 2-MePh CF3t-Bu 6-Me H 2-CNPh CF3Me 6-Me H 2-FPh CF3Et 6-Me H 2，6-F2Ph CF3i-Pr 6-Me 4-Br2，4-F2Ph CF3t-Bu 6-Me H 2，5-F2Ph CF3Me 6-Me 4-I 2-MeOPhCF3Et 6-Me H 3-Cl-2-pyridyl CF3i-Pr 6-Me H 3-Cl-2-pyridl OCF3t-Bu 6-Me H 3-Cl-2-pyridyl Brpropargyl 6-Me H 3-Cl-2-pyridyl ClEt 6-Me 4-Br3-Cl-2-pyridyl SCHF2i-Pr 6-Me H 3-F-2-pyridyl CF3t-Bu 6-Me H 3-CF3-2-pyridyl CF3Me 6-Me H 3-Me-2-pyridyl CF3Et 6-Me H 3-Br-2-pyridyl CF3
R3R4aR4bRvaRvbi-Pr 6-Me 4-Cl3-Br-2-pyridylOCF3t-Bu 6-Me H 3-Br-2-pyridylBri-Pr 6-Me H 3-Br-2-pyridylClMe 3-Cl H H CF3Et 3-Br 5-MeH OCF3i-Pr 3-Cl H H OCF3t-Bu 3-Cl 5-ClMeBrMe 3-Cl H EtBrEt 3-Cl H MeCli-Pr 3-Cl 5-BrEtClt-Bu 3-Cl H MeIpropargyl 3-Cl H MeCF3cyclopropyl3-Cl H MeOCF3i-Pr 3-Cl 5-ClMeCF3t-Bu 3-Cl H MeSCF3Me 3-F H MeSCHF2Et 3-Cl H MeOCHF2i-Pr 3-Cl 5-CNMeCF3t-Bu 3-Cl H MeC2F5propargyl 3-Cl H MeC2F5cyclopropyl3-Cl H EtCF3i-Pr 3-Cl H n-Pr CF3t-Bu 3-Cl 5-Bri-Pr CF3Me 3-Cl H ClCF3Et 3-Br H F CF3i-Pr 3-Cl H MeSMet-Bu 3-Cl 5-ClMeOMeMe 3-Cl H MeOEtEt 3-Cl H Men-C3F7i-Pr 3-Cl H Mei-C3F7t-Bu 3-Cl 5-F MeEtpropargyl 3-Cl H MeOCF2CH2Et 3-Cl H MeSCF2CHF2i-Pr 3-Br H MeSO2Met-Bu 3-Cl 5-ClMeSO2CF3Me 3-Cl H CF3CF3
R3R4aR4bRvaRvbEt 3-CN H CF3Mei-pr 3-Cl H OMe CF3t-Bu 3-Cl H H CF3cyclopropyl3-Cl 5-BrH OCHF2Et 3-Cl H H C2F5i-Pr 3-Cl H H C2F5t-Bu 3-Cl H H OCF3Me 3-F H H OCF2CHF2Et 3-Cl H H SCF2CHF2i-pr 3-Cl 5-ClH n-C3F7t-Bu 3-Cl H H i-C3F7propargyl 3-Cl H H BrEt 3-Cl H H Cli-pr 3-Cl H H SCF3t-Bu 3-Cl 5-BrPhCF3cyclopropyl3-Cl H PhClEt 3-Cl H PhBri-pr 3-Br H 2-pyridyl CF3t-Bu 3-Cl H 2-pyridyl ClMe 3-Cl H 2-ClPhCF3Et 3-Cl 5-Cl2-ClPhOCF3i-Pr 3-Cl H 2-ClPhBrt-Bu 3-I H 2-ClPhClMe 3-Cl 5-Me2-ClPhSCHF2propargyl 3-Cl H 2-BrPhCF3i-Pr 3-Cl H 2-MePhCF3t-Bu 3-Cl 5-CN2-CNPhCF3Me 3-Cl H 2-FPh CF3Et 3-Cl H 2，6-F2PhCF3i-Pr 3-Cl 5-Br2，4-F2PhCF3t-Bu 3-F H 2，5-F2PhCF3Me 3-Cl 5-I 2-MeOPh CF3Et 3-Cl H 3-Cl-2-pyridylCF3i-Pr 3-CN H 3-Cl-2-pyridylOCF3t-Bu 3-Cl H 3-Cl-2-pyridylBrpropargyl 3-Cl H 3-Cl-2-pyridylCl
R3R4aR4bRvaRvbEt 3-Cl 5-Br3-Cl-2-pyridyl SCHF2i-Pr 3-Cl H 3-F-2-pyridyl CF3t-Bu 3-Br H 3-CF3-2-pyridyl CF3Me 3-Cl H 3-Me-2-pyridyl CF3Et 3-Cl H 3-Br-2-pyridyl CF3i-Pr 3-Cl 5-Cl3-Br-2-pyridyl OCF3t-Bu 3-Cl H 3-Br-2-pyridyl Bri-Pr 3-Cl H 3-Br-2-pyridyl ClMe 6-Cl H H CF3Et 6-Br 4-MeH OCF3i-Pr 6-Cl H H OCF3t-Bu 6-Cl Cl Me BrMe 6-Cl H Et BrEt 6-Cl H Me Cli-Pr 6-F 4-BrEt Clt-Bu 6-Cl H Me Ipropargyl 6-Cl H Me CF3cyclopropyl6-Cl H Me OCF3i-Pr 6-Cl 4-ClMe CF3t-Bu 6-Cl H Me SCF3Me 6-Cl H Me SCHF2Et 6-Cl H Me OCHF2i-Pr 6-I 4-CNMe CF3t-Bu 6-Cl H Me C2F5propargyl 6-Cl H Me C2F5cyclopropyl6-Cl H Et CF3i-Pr 6-Cl H n-Pr CF3t-Bu 6-Cl 4-Bri-Pr CF3Me 6-Cl H Cl CF3Et 6-F H F CF3i-Pr 6-Cl H Me SMet-Bu 6-Cl 4-ClMe OMeMe 6-Cl H Me OEtEt 6-I H Me n-C3F7i-Pr 6-Cl H Me i-C3F7t-Bu 6-Cl 4-F Me Et
R3R4aR4bRvaRvbpropargyl 6-Cl H Me OCF2CHF2Et 6-Cl H Me SCF2CHF2i-Pr 6-Cl H Me SO2Met-Bu 6-Cl 4-ClMe SO2CF3Me 6-Cl H CF3CF3Et 6-Cl H CF3Mei-Pr 6-Cl H OMe CF3t-Bu 6-Br H HCF3cyclopropyl6-Cl 4-BrHOCHF2Et 6-Cl H HC2F5i-Pr 6-Cl H HC2F5t-Bu 6-F 4-MeHOCF3Me 6-Cl H HOCF2CHF2Et 6-Cl H HSCF2CHF2i-Pr 6-CN 4-C Hn-C3F7t-Bu 6-Cl H Hi-C3F7propargyl 6-Cl H HBrEt 6-Cl H HCli-Pr 6-Cl H HSCF3t-Bu 6-Cl 4-BrPh CF3cyclopropyl6-Cl H Ph ClEt 6-F H Ph Bri-Pr 6-Cl H 2-pyridylCF3t-Bu 6-Cl H 2-pyridylClMe 6-Cl H 2-ClPh CF3Et 6-Br 4-Cl2-ClPh OCF3i-Pr 6-Cl H 2-ClPh Brt-Bu 6-Cl H 2-ClPh ClMe 6-Cl H 2-ClPh SCHF2propargyl 6-Cl H 2-BrPh CF3i-Pr 6-Br H 2-MePh CF3t-Bu 6-Cl 4-CN2-CNPh CF3Me 6-Cl H 2-FPhCF3Et 6-Cl H 2，6-F2Ph CF3i-Pr 6-Cl 4-Br2，4-F2Ph CF3t-Bu 6-CN H 2，5-F2Ph CF3
R3R4aR4bRvaRvbMe 6-Cl 4-I 2-MeOPhCF3Et 6-Cl H 3-Cl-2-pyridyl CF3i-Pr 6-Br H 3-Cl-2-pyridyl OCF3t-Bu 6-Cl H 3-Cl-2-pyridyl Brpropargyl 6-Cl H 3-Cl-2-pyridyl ClEt 6-Cl 4-Br3-Cl-2-pyridyl SCHF2i-Pr 6-Cl H 3-F-2-pyridyl CF3t-Bu 6-Cl H 3-CF3-2-pyridyl CF3Me 6-Cl H 3-Me-2-pyridyl CF3Et 6-Cl H 3-Br-2-pyridyl CF3i-Pr 6-Cl 4-Cl3-Br-2-pyridyl OCF3t-Bu 6-Cl H 3-Br-2-pyridyl Bri-Pr 6-Cl H 3-Br-2-pyridyl ClTable2 R3R4aR4bRvaRvbMe 3-Me H H CF3Et 3-Me 5-MeH OCF3i-Pr 3-Me H H OCF3t-Bu 3-Me 5-ClMe BrMe 3-Me H Et BrEt 3-Me H Me Cli-Pr 3-Me 5-BrEt Clt-Bu 3-Me H Me Ipropargyl 3-Me H Me CF3cyclopropyl3-Me H Me OCF3
R3R4aR4bRvaRvbi-Pr 3-Me 5-Cl Me CF3t-Bu 3-Me H Me SCF3Me 3-Me 5-CN Me SCHF2Et 3-Me H Me OCHF2i-Pr 3-Me H Me CF3t-Bu 3-Me H Me C2F5propargyl 3-Me H Me C2F5cyclopropyl3-Me H Et CF3i-Pr 3-Me H n-PrCF3t-Bu 3-Me 5-Br i-PrCF3Me 3-Me H Cl CF3Et 3-Me H F CF3i-Pr 3-Me H Me SMet-Bu 3-Me 5-Cl Me OMeMe 3-Me H Me OEtEt 3-Me H Me n-C3F7i-Pr 3-Me H Me i-C3F7t-Bu 3-Me 5-F Me Etpropargyl 3-Me H Me OCF2CHF2Et 3-Me H Me SCF2CHF2i-Pr 3-Me H Me SO2Met-Bu 3-Me 5-Cl Me SO2CF3Me 3-Me H CF3CF3Et 3-Me H CF3Mei-Pr 3-Me H OMe CF3t-Bu 3-Me H H CF3cyclopropyl3-Me 5-Br H OCHF2Et 3-Me H H C2F5i-Pr 3-Me 5-Me H C2F5t-Bu 3-Me H H OCF3Me 3-Me H H OCF2CHF2Et 3-Me H H SCF2CHF2i-Pr 3-Me 5-Cl H n-C3F7t-Bu 3-Me H H i-C3F7propargyl 3-Me H H BrEt 3-Me H H Cl
R3R4aR4bRvaRvbi-Pr 3-Me H H SCF3t-Bu 3-Me 5-BrPh CF3cyclopropyl3-Me H Ph ClEt 3-Me H Ph Bri-Pr 3-Me H 2-pyridyl CF3t-Bu 3-Me H 2-pyridyl ClMe 3-Me H 2-ClPh CF3Et 3-Me 5-Cl2-ClPh OCF3i-Pr 3-Me H 2-ClPh Brt-Bu 3-Me H 2-ClPh ClMe 3-Me H 2-ClPh SCHF2propargyl 3-Me H 2-BrPh CF3i-Pr 3-Me 5-CN2-MePh CF3t-Bu 3-Me H 2-CNPh CF3Me 3-Me H 2-FPh CF3Et 3-Me H 2，6-F2Ph CF3i-Pr 3-Me 5-Br2，4-F2Ph CF3t-Bu 3-Me H 2，5-F2Ph CF3Me 3-Me 5-I 2-MeOPhCF3Et 3-Me H 3-Cl-2-pyridyl CF3i-Pr 3-Me 5-Me3-Cl-2-pyridyl OCF3t-Bu 3-Me H 3-Cl-2-pyridyl Brpropargyl 3-Me H 3-Cl-2-pyridyl ClEt 3-Me 5-Br3-Cl-2-pyridyl SCHF2i-Pr 3-Me H 3-F-2-pyridyl CF3t-Bu 3-Me H 3-CF3-2-pyridyl CF3Me 3-Me H 3-Me-2-pyridyl CF3Et 3-Me H 3-Br-2-pyridyl CF3i-Pr 3-Me 5-Cl3-Br-2-pyridyl OCF3t-Bu 3-Me H 3-Br-2-pyridyl Bri-Pr 3-Me H 3-Br-2-pyridyl ClMe 6-Me H H CF3Et 6-Me 4-MeH OCF3i-Pr 6-Me H H OCF3t-Bu 6-Me Cl Me BrMe 6-Me H Et Br
R3R4aR4bRvaRvbEt 6-Me H MeCli-Pr 6-Me 4-Br EtClt-Bu 6-Me H MeIpropargyl 6-Me H MeCF3cyclopropyl6-Me H MeOCF3i-Pr 6-Me 4-Cl MeCF3t-Bu 6-Me H MeSCF3Me 6-Me H MeSCHF2Et 6-Me H MeOCHF2i-Pr 6-Me 4-CN MeCF3t-Bu 6-Me H MeC2F5propargyl 6-Me H MeC2F5cyclopropyl6-Me H EtCF3i-Pr 6-Me H n-Pr CF3t-Bu 6-Me 4-Br i-Pr CF3Me 6-Me H ClCF3Et 6-Me H F CF3i-Pr 6-Me H MeSMet-Bu 6-Me 4-Cl MeOMeMe 6-Me H MeOEtEt 6-Me H Men-C3F7i-Pr 6-Me H Mei-C3F7t-Bu 6-Me 4-F MeEtpropargyl 6-Me H MeOCF2CHF2Et 6-Me H MeSCF2CHF2i-Pr 6-Me H MeSO2Met-Bu 6-Me 4-Cl MeSO2CF3Me 6-Me H CF3CF3Et 6-Me H CF3Mei-Pr 6-Me H OMe CF3t-Bu 6-Me H H CF3cyclopropyl6-Me 4-Br H OCHF2Et 6-Me H H C2F5i-Pr 6-Me H H C2F5t-Bu 6-Me 4-Me H OCF3Me 6-Me H H OCF2CHF2
R3R4aR4bRvaRvbEt 6-Me H H SCF2CHF2i-Pr 6-Me 4-ClH n-C3F7t-Bu 6-Me H H i-C3F7propargyl 6-Me H H BrEt 6-Me H H Cli-Pr 6-Me H H SCF3t-Bu 6-Me 4-BrPh CF3cyclopropyl6-Me H Ph ClEt 6-Me H Ph Bri-Pr 6-Me H 2-pyridyl CF3t-Bu 6-Me H 2-pyridyl ClMe 6-Me H 2-ClPh CF3Et 6-Me 4-Cl2-ClPh OCF3i-Pr 6-Me H 2-ClPh Brt-Bu 6-Me 4-CN2-ClPh ClMe 6-Me H 2-ClPh SCHF2propargyl 6-Me H 2-BrPh CF3i-Pr 6-Me H 2-MePh CF3t-Bu 6-Me H 2-CNPh CF3Me 6-Me H 2-FPh CF3Et 6-Me H 2，6-F2Ph CF3i-Pr 6-Me 4-Br2，4-F2Ph CF3t-Bu 6-Me H 2，5-F2Ph CF3Me 6-Me 4-I 2-MeOPhCF3Et 6-Me H 3-Cl-2-pyridyl CF3i-Pr 6-Me H 3-Cl-2-pyridyl OCF3t-Bu 6-Me H 3-Cl-2-pyridyl Brpropargyl 6-Me H 3-Cl-2-pyridyl ClEt 6-Me 4-Br3-Cl-2-pyridyl SCHF2i-Pr 6-Me H 3-F-2-pyridyl CF3t-Bu 6-Me H 3-CF3-2-pyridyl CF3Me 6-Me H 3-Me-2-pyridyl CF3Et 6-Me H 3-Br-2-pyridyl CF3i-Pr 6-Me 4-Cl3-Br-2-pyridyl OCF3t-Bu 6-Me H 3-Br-2-pyridyl Bri-Pr 6-Me H 3-Br-2-pyridyl Cl
R3R4aR4bRvaRvbMe 3-Cl H H CF3Et 3-Br 5-Me H OCF3i-Pr 3-Cl H H OCF3t-Bu 3-Cl 5-Cl Me BrMe 3-Cl H Et BrEt 3-Cl H Me Cli-Pr 3-Cl 5-Br Et Clt-Bu 3-Cl H Me Ipropargyl 3-Cl H Me CF3cyclopropyl3-Cl H Me OCF3i-Pr 3-Cl 5-Cl Me CF3t-Bu 3-Cl H Me SCF3Me 3-F H Me SCHF2Et 3-Cl H Me OCHF2i-Pr 3-Cl 5-CN Me CF3t-Bu 3-Cl H Me C2F5propargyl 3-Cl H Me C2F5cyclopropyl3-Cl H Et CF3i-Pr 3-Cl H n-PrCF3t-Bu 3-Cl 5-Br i-PrCF3Me 3-Cl H Cl CF3Et 3-Br H F CF3i-Pr 3-Cl H Me SMet-Bu 3-Cl 5-Cl Me OMeMe 3-Cl H Me OEtEt 3-Cl H Me n-C3F7i-Pr 3-Cl H Me i-C3F7t-Bu 3-Cl 5-F Me Etpropargyl 3-Cl H Me OCF2CHF2Et 3-Cl H Me SCF2CHF2i-Pr 3-Br H Me SO2Met-Bu 3-Cl 5-Cl Me SO2CF3Me 3-Cl H CF3CF3Et 3-CN H CF3Mei-Pr 3-Cl H OMe CF3t-Bu 3-Cl H H CF3
R3R4aR4bRvaRvbcyclopropyl3-Cl 5-BrH OCHF2Et 3-Cl H H C2F5i-Pr 3-Cl H H C2F5t-Bu 3-Cl H H OCF3Me 3-F H H OCF2CHF2Et 3-Cl H H SCF2CHF2i-Pr 3-Cl 5-ClH n-C3F7t-Bu 3-Cl H H i-C3F7propargyl 3-Cl H H BrEt 3-Cl H H Cli-Pr 3-Cl H H SCF3t-Bu 3-Cl 5-BrPh CF3cyclopropyl3-Cl H Ph ClEt 3-Cl H Ph Bri-Pr 3-Br H 2-pyridyl CF3t-Bu 3-Cl H 2-pyridyl ClMe 3-Cl H 2-ClPh CF3Et 3-Cl 5-Cl2-ClPh OCF3i-Pr 3-Cl H 2-ClPh Brt-Bu 3-I H 2-ClPh ClMe 3-Cl 5-Me2-ClPh SCHF2propargyl 3-Cl H 2-BrPh CF3i-Pr 3-Cl H 2-MePh CF3t-Bu 3-Cl 5-CN2-CNPh CF3Me 3-Cl H 2-FPh CF3Et 3-Cl H 2，6-F2Ph CF3i-Pr 3-Cl 5-Br2，4-F2Ph CF3t-Bu 3-F H 2，5-F2Ph CF3Me 3-Cl 5-I 2-MeOPhCF3Et 3-Cl H 3-Cl-2-pyridyl CF3i-Pr 3-CN H 3-Cl-2-pyridyl OCF3t-Bu 3-Cl H 3-Cl-2-pyridyl Brpropargyl 3-Cl H 3-Cl-2-pyridyl ClEt 3-Cl 5-Br3-Cl-2-pyridyl SCHF2i-Pr 3-Cl H 3-F-2-pyridyl CF3t-Bu 3-Br H 3-CF3-2-pyridyl CF3
R3R4aR4bRvaRvbMe 3-Cl H 3-Me-2-pyridylCF3Et 3-Cl H 3-Br-2-pyridylCF3i-Pr 3-Cl 5-Cl3-Br-2-PyridylOCF3t-Bu 3-Cl H 3-Br-2-pyridylBri-Pr 3-Cl H 3-Br-2-pyridylClMe 6-Cl H H CF3Et 6-Br 4-MeH OCF3i-Pr 6-Cl H H OCF3t-Bu 6-Cl Cl MeBrMe 6-Cl H EtBrEt 6-Cl H MeCli-Pr 6-F 4-BrEtClt-Bu 6-Cl H MeIpropargyl 6-Cl H MeCF3cyclopropyl6-Cl H MeOCF3i-Pr 6-Cl 4-ClMeCF3t-Bu 6-Cl H MeSCF3Me 6-Cl H MeSCHF2Et 6-Cl H MeOCHF2i-Pr 6-I 4-CNMeCF3t-Bu 6-Cl H MeC2F5propargyl 6-Cl H MeC2F5cyclopropyl6-Cl H EtCF3i-Pr 6-Cl H n-Pr CF3t-Bu 6-Cl 4-Bri-Pr CF3Me 6-Cl H ClCF3Et 6-F H F CF3i-Pr 6-Cl H MeSMet-Bu 6-Cl 4-ClMeOMeMe 6-Cl H MeOEtEt 6-I H Men-C3F7i-Pr 6-Cl H Mei-C3F7t-Bu 6-Cl 4-F MeEtpropargyl 6-Cl H MeOCF2CHF2Et 6-Cl H MeSCF2CHF2i-Pr 6-Cl H MeSO2Me
R3R4aR4bRvaRvbt-Bu 6-Cl 4-Cl MeSO2CF3Me 6-Cl H CF3CF3Et 6-Cl H CF3Mei-Pr 6-Cl H OMe CF3t-Bu 6-Br H H CF3cyclopropyl6-Cl 4-Br H OCHF2Et 6-Cl H H C2F5i-Pr 6-Cl H H C2F5t-Bu 6-F 4-Me H OCF3Me 6-Cl H H OCF2CHF2Et 6-Cl H H SCF2CHF2i-Pr 6-CN 4-Cl H n-C3F7t-Bu 6-Cl H H i-C3F7propargyl 6-Cl H H BrEt 6-Cl H H Cli-Pr 6-Cl H H SCF3t-Bu 6-Cl 4-Br PhCF3cyclopropyl6-Cl H PhClEt 6-F H PhBri-Pr 6-Cl H 2-pyridyl CF3t-Bu 6-Cl H 2-pyridyl ClMe 6-Cl H 2-ClPhCF3Et 6-Br 4-Cl 2-ClPhOCF3i-Pr 6-Cl H 2-ClPhBrt-Bu 6-Cl H 2-ClPhClMe 6-Cl H 2-ClPhSCHF2propargyl 6-Cl H 2-BrPhCF3i-Pr 6-Br H 2-MePhCF3t-Bu 6-Cl 4-CN 2-CNPhCF3Me 6-Cl H 2-FPh CF3Et 6-Cl H 2，6-F2PhCF3i-Pr 6-Cl 4-Br 2，4-F2PhCF3t-Bu 6-CN H 2，5-F2PhCF3Me 6-Cl 4-I 2-MeOPh CF3Et 6-Cl H 3-Cl-2-pyridylCF3i-Pr 6-Br H 3-Cl-2-pyridylOCF3
R3R4aR4bRvaRvbt-Bu 6-Cl H 3-Cl-2-pyridyl Brpropargyl 6-Cl H 3-Cl-2-pyridyl ClEt 6-Cl 4-Br 3-Cl-2-pyridyl SCHF2i-Pr 6-Cl H 3-F-2-pyridyl CF3t-Bu 6-Cl H 3-CF3-2-pyridyl CF3Me 6-Cl H 3-Me-2-pyridyl CF3Et 6-Cl H 3-Br-2-pyridyl CF3i-Pr 6-Cl 4-Cl 3-Br-2-pyridyl OCF3t-Bu 6-Cl H 3-Br-2-pyridyl Bri-Pr 6-Cl H 3-Br-2-pyridyl ClTable 3 R3R4aR4bRvaRvbMe 3-Me H H CF3Et 3-Me 5-Me H OCF3i-Pr 3-Me H H OCF3t-Bu 3-Me 5-Cl Me BrMe 3-Me H Et BrEt 3-Me H Me Cli-Pr 3-Me 5-Br Et Clt-Bu 3-Me H Me Ipropargyl 3-Me H Me CF3cyclopropyl3-Me H Me OCF3i-Pr 3-Me 5-Cl Me CF3t-Bu 3-Me H Me SCF3Me 3-Me 5-CN Me SCHF2Et 3-Me H Me OCHF2i-Pr 3-Me H Me CF3
R3R4aR4bRvaRvbt-Bu 3-Me H Me C2F5propargyl 3-Me H Me C2F5cyclopropyl3-Me H Et CF3i-Pr 3-Me H n-Pr CF3t-Bu 3-Me 5-Br i-Pr CF3Me 3-Me H Cl CF3Et 3-Me H FCF3i-Pr 3-Me H Me SMet-Bu 3-Me 5-Cl Me OMeMe 3-Me H Me OEtEt 3-Me H Me n-C3F7i-Pr 3-Me H Me i-C3F7t-Bu 3-Me 5-F Me Etpropargyl 3-Me H Me OCF2CHF2Et 3-Me H Me SCF2CHF2i-Pr 3-Me H Me SO2Met-Bu 3-Me 5-Cl Me SO2CF3Me 3-Me H CF3CF3Et 3-Me H CF3Mei-Pr 3-Me H OMe CF3t-Bu 3-Me H HCF3cyclopropyl3-Me 5-Br HOCHF2Et 3-Me H HC2F5i-Pr 3-Me 5-Me HC2F5t-Bu 3-Me H HOCF3Me 3-Me H HOCF2CHF2Et 3-Me H HSCF2CHF2i-Pr 3-Me 5-Cl Hn-C3F7t-Bu 3-Me H Hi-C3F7propargyl 3-Me H HBrEt 3-Me H HCli-Pr 3-Me H HSCF3t-Bu 3-Me 5-Br Ph CF3cyclopropyl3-Me H Ph ClEt 3-Me H Ph Bri-Pr 3-Me H 2-pyridylCF3
R3R4aR4bRvaRvbt-Bu 3-Me H 2-pyridyl ClMe 3-Me H 2-ClPh CF3Et 3-Me 5-Cl 2-ClPh OCF3i-Pr 3-Me H 2-ClPh Brt-Bu 3-Me H 2-ClPh ClMe 3-Me H 2-ClPh SCHF2propargyl 3-Me H 2-BrPh CF3i-Pr 3-Me 5-CN 2-MePh CF3t-Bu 3-Me H 2-CNPh CF3Me 3-Me H 2-FPh CF3Et 3-Me H 2，6-F2Ph CF3i-Pr 3-Me 5-Br 2，4-F2Ph CF3t-Bu 3-Me H 2，5-F2Ph CF3Me 3-Me 5-I 2-MeOPhCF3Et 3-Me H 3-Cl-2-pyridyl CF3i-Pr 3-Me 5-Me 3-Cl-2-pyridyl OCF3t-Bu 3-Me H 3-Cl-2-pyridyl Brpropargyl 3-Me H 3-Cl-2-pyridyl ClEt 3-Me 5-Br 3-Cl-2-pyridyl SCHF2i-Pr 3-Me H 3-F-2-pyridyl CF3t-Bu 3-Me H 3-CF3-2-pyridyl CF3Me 3-Me H 3-Me-2-pyridyl CF3Et 3-Me H 3-Br-2-pyridyl CF3i-Pr 3-Me 5-Cl 3-Br-2-pyridyl OCF3t-Bu 3-Me H 3-Br-2-pyridyl Bri-Pr 3-Me H 3-Br-2-pyridyl ClMe 6-Me H H CF3Et 6-Me 4-Me H OCF3i-Pr 6-Me H H OCF3t-Bu 6-Me ClMe BrMe 6-Me H Et BrEt 6-Me H Me Cli-Pr 6-Me 4-Br Et Clt-Bu 6-Me H Me Ipropargyl 6-Me H Me CF3cyclopropyl6-Me H Me OCF3
R3R4aR4bRvaRvbi-Pr 6-Me 4-Cl Me CF3t-Bu 6-Me H Me SCF3Me 6-Me H Me SCHF2Et 6-Me H Me OCHF2i-Pr 6-Me 4-CN Me CF3t-Bu 6-Me H Me C2F5propargyl 6-Me H Me C2F5cyclopropyl6-Me H Et CF3i-Pr 6-Me H n-PrCF3t-Bu 6-Me 4-Br i-PrCF3Me 6-Me H Cl CF3Et 6-Me H F CF3i-Pr 6-Me H Me SMet-Bu 6-Me 4-Cl Me OMeMe 6-Me H Me OEtEt 6-Me H Me n-C3F7i-Pr 6-Me H Me i-C3F7t-Bu 6-Me 4-F Me Etpropargyl 6-Me H Me OCF2CHF2Et 6-Me H Me SCF2CHF2i-Pr 6-Me H Me SO2Met-Bu 6-Me 4-Cl Me SO2CF3Me 6-Me H CF3CF3Et 6-Me H CF3Mei-Pr 6-Me H OMe CF3t-Bu 6-Me H H CF3cyclopropyl6-Me 4-Br H OCHF2Et 6-Me H H C2F5i-Pr 6-Me H H C2F5t-Bu 6-Me 4-Me H OCF3Me 6-Me H H OCF2CHF2Et 6-Me H H SCF2CHF2i-Pr 6-Me 4-Cl H n-C3F7t-Bu 6-Me H H i-C3F7propargyl 6-Me H H BrEt 6-Me H H Cl
R3R4aR4bRvaRvbi-Pr 6-Me H H SCF3t-Bu 6-Me 4-Br Ph CF3cyclopropyl6-Me H Ph ClEt 6-Me H Ph Bri-Pr 6-Me H 2-pyridyl CF3t-Bu 6-Me H 2-pyridyl ClMe 6-Me H 2-ClPh CF3Et 6-Me 4-Cl 2-ClPh OCF3i-Pr 6-Me H 2-ClPh Brt-Bu 6-Me 4-CN 2-ClPh ClMe 6-Me H 2-ClPh SCHF2propargyl 6-Me H 2-BrPh CF3i-Pr 6-Me H 2-MePh CF3t-Bu 6-Me H 2-CNPh CF3Me 6-Me H 2-FPh CF3Et 6-Me H 2，6-F2Ph CF3i-Pr 6-Me 4-Br 2，4-F2Ph CF3t-Bu 6-Me H 2，5-F2Ph CF3Me 6-Me 4-I 2-MeOPhCF3Et 6-Me H 3-Cl-2-pyridyl CF3i-Pr 6-Me H 3-Cl-2-pyridyl OCF3t-Bu 6-Me H 3-Cl-2-pyridyl Brpropargyl 6-Me H 3-Cl-2-pyridyl ClEt 6-Me 4-Br 3-Cl-2-pyridyl SCHF2i-Pr 6-Me H 3-F-2-pyridyl CF3t-Bu 6-Me H 3-CF3-2-pyridyl CF3Me 6-Me H 3-Me-2-pyridyl CF3Et 6-Me H 3-Br-2-pyridyl CF3i-Pr 6-Me 4-Cl 3-Br-2-pyridyl OCF3t-Bu 6-Me H 3-Br-2-pyridyl Bri-Pr 6-Me H 3-Br-2-pyridyl ClMe 3-Cl H H CF3Et 3-Br 5-Me H OCF3i-Pr 3-Cl H H OCF3t-Bu 3-Cl 5-Cl Me BrMe 3-Cl H Et Br
R3R4aR4bRvaRvbEt 3-Cl H MeCli-Pr 3-Cl 5-Br EtClt-Bu 3-Cl H MeIpropargyl 3-Cl H MeCF3cyclopropyl3-Cl H MeOCF3i-Pr 3-Cl 5-Cl MeCF3t-Bu 3-Cl H MeSCF3Me 3-F H MeSCHF2Et 3-Cl H MeOCHF2i-Pr 3-Cl 5-CN MeCF3t-Bu 3-Cl H MeC2F5propargyl 3-Cl H MeC2F5cyclopropyl3-Cl H EtCF3i-Pr 3-Cl H n-Pr CF3t-Bu 3-Cl 5-Br i-Pr CF3Me 3-Cl H ClCF3Et 3-Br H F CF3i-Pr 3-Cl H MeSMet-Bu 3-Cl 5-Cl MeOMeMe 3-Cl H MeOEtEt 3-Cl H Men-C3F7i-Pr 3-Cl H Mei-C3F7t-Bu 3-Cl 5-F MeEtpropargyl 3-Cl H MeOCF2CHF2Et 3-Cl H MeSCF2CHF2i-Pr 3-Br H MeSO2Met-Bu 3-Cl 5-Cl MeSO2CF3Me 3-Cl H CF3CF3Et 3-CN H CF3Mei-Pr 3-Cl H OMe CF3t-Bu 3-Cl H H CF3cyclopropyl3-Cl 5-Br H OCHF2Et 3-Cl H H C2F5i-Pr 3-Cl H H C2F5t-Bu 3-Cl H H OCF3Me 3-F H H OCF2CHF2
R3R4aR4bRvaRvbEt 3-Cl H H SCF2CHF2i-Pr 3-Cl 5-Cl H n-C3F7t-Bu 3-Cl H H i-C3F7propargyl 3-Cl H H BrEt 3-Cl H H Cli-Pr 3-Cl H H SCF3t-Bu 3-Cl 5-Br Ph CF3cyclopropyl3-Cl H Ph ClEt 3-Cl H Ph Bri-Pr 3-Br H 2-pyridyl CF3t-Bu 3-Cl H 2-pyridyl ClMe 3-Cl H 2-ClPh CF3Et 3-Cl 5-Cl 2-ClPh OCF3i-Pr 3-Cl H 2-ClPh Brt-Bu 3-I H 2-ClPh ClMe 3-Cl 5-Me 2-ClPh SCHF2propargyl 3-Cl H 2-BrPh CF3i-Pr 3-Cl H 2-MePh CF3t-Bu 3-Cl 5-CN 2-CNPh CF3Me 3-Cl H 2-FPh CF3Et 3-Cl H 2，6-F2Ph CF3i-Pr 3-Cl 5-Br 2，4-F2Ph CF3t-Bu 3-F H 2，5-F2Ph CF3Me 3-Cl 5-I 2-MeOPhCF3Et 3-Cl H 3-Cl-2-pyridyl CF3i-Pr 3-CN H 3-Cl-2-pyridyl OCF3t-Bu 3-Cl H 3-Cl-2-pyridyl Brpropargyl 3-Cl H 3-Cl-2-pyridyl ClEt 3-Cl 5-Br 3-Cl-2-pyridyl SCHF2i-Pr 3-Cl H 3-F-2-pyridyl CF3t-Bu 3-Br H 3-CF3-2-pyridyl CF3Me 3-Cl H 3-Me-2-pyridyl CF3Et 3-Cl H 3-Br-2-pyridyl CF3i-Pr 3-Cl 5-Cl 3-Br-2-pyridyl OCF3t-Bu 3-Cl H 3-Br-2-pyridyl Bri-Pr 3-Cl H 3-Br-2-pyridyl Cl
R3R4aR4bRvaRvbMe 6-Cl H H CF3Et 6-Br 4-Me H OCF3i-Pr 6-Cl H H OCF3t-Bu 6-Cl ClMeBrMe 6-Cl H EtBrEt 6-Cl H MeCli-Pr 6-F 4-Br EtClt-Bu 6-Cl H MeIpropargyl 6-Cl H MeCF3cyclopropyl6-Cl H MeOCF3i-Pr 6-Cl 4-Cl MeCF3t-Bu 6-Cl H MeSCF3Me 6-Cl H MeSCHF2Et 6-Cl H MeOCHF2i-Pr 6-I 4-CN MeCF3t-Bu 6-Cl H MeC2F5propargyl 6-Cl H MeC2F5cyclopropyl6-Cl H EtCf3i-Pr 6-Cl H n-Pr CF3t-Bu 6-Cl 4-Br i-Pr CF3Me 6-Cl H ClCF3Et 6-F H F CF3i-Pr 6-Cl H MeSMet-Bu 6-Cl 4-Cl MeOMeMe 6-Cl H MeOEtEt 6-I H Men-C3F7i-Pr 6-Cl H Mei-C3F7t-Bu 6-Cl 4-F MeEtpropargyl 6-Cl H MeOCF2CHF2Et 6-Cl H MeSCF2CHF2i-Pr 6-Cl H MeSO2Met-Bu 6-Cl 4-Cl MeSO2CF3Me 6-Cl H CF3CF3Et 6-Cl H CF3Mei-Pr 6-Cl H OMe CF3t-Bu 6-Br H H CF3
R3R4aR4bRvaRvbcyclopropyl6-Cl 4-Br H OCHF2Et 6-Cl H H C2F5i-Pr 6-Cl H H C2F5t-Bu 6-F 4-Me H OCF3Me 6-Cl H H OCF2CHF2Et 6-Cl H H SCF2CHF2i-Pr 6-CN 4-Cl H n-C3F7t-Bu 6-Cl H H i-C3F7propargyl 6-Cl H H BrEt 6-Cl H H Cli-Pr 6-Cl H H SCF3t-Bu 6-Cl 4-Br Ph CF3cyclopropyl6-Cl H Ph ClEt 6-F H Ph Bri-Pr 6-Cl H 2-pyridyl CF3t-Bu 6-Cl H 2-pyridyl ClMe 6-Cl H 2-ClPh CF3Et 6-Br 4-Cl 2-ClPh OCF3i-Pr 6-Cl H 2-ClPh Brt-Bu 6-Cl H 2-ClPh ClMe 6-Cl H 2-ClPh SCHF2propargyl 6-Cl H 2-BrPh CF3i-Pr 6-Br H 2-MePh CF3t-Bu 6-Cl 4-CN 2-CNPh CF3Me 6-Cl H 2-FPh CF3Et 6-Cl H 2，6-F2Ph CF3i-Pr 6-Cl 4-Br 2，4-F2Ph CF3t-Bu 6-CN H 2，5-F2Ph CF3Me 6-Cl 4-I 2-MeOPhCF3Et 6-Cl H 3-Cl-2-pyridyl CF3i-Pr 6-Br H 3-Cl-2-pyridyl OCF3t-Bu 6-Cl H 3-Cl-2-pyridyl Brpropargyl 6-Cl H 3-Cl-2-pyridyl ClEt 6-Cl 4-Br 3-Cl-2-pyridyl SCHF2i-Pr 6-Cl H 3-F-2-pyridyl CF3t-Bu 6-Cl H 3-CF3-2-pyridyl CF3
R3R4aR4bRvaRvbMe 6-Cl H 3-Me-2-pyridylCF3Et 6-Cl H 3-Br-2-pyridylCF3i-Pr 6-Cl 4-Cl 3-Br-2-pyridylOCF3t-Bu 6-Cl H 3-Br-2-pyridylBri-Pr 6-Cl H 3-Br-2-pyridylClTable 4 R3R4aR4bRvaRvbMe 3-Me H H CF3Et 3-Me 5-Me H OCF3i-Pr 3-Me H H OCF3t-Bu 3-Me 5-Cl MeBrMe 3-Me H EtBrEt 3-Me H MeCli-Pr 3-Me 5-Br EtClt-Bu 3-Me H MeIpropargyl 3-Me H MeCF3cyclopropyl3-Me H MeOCF3i-Pr 3-Me 5-Cl MeCF3t-Bu 3-Me H MeSCF3Me 3-Me 5-CN MeSCHF2Et 3-Me H MeOCHF2i-Pr 3-Me H MeCF3t-Bu 3-Me H MeC2F5propargyl 3-Me H MeC2F5cyclopropyl3-Me H EtCF3i-Pr 3-Me H n-Pr CF3t-Bu 3-Me 5-Br i-Pr CF3
R3R4aR4bRvaRvbMe 3-MeH Cl CF3Et 3-MeH FCF3i-Pr 3-MeH Me SMet-Bu 3-Me5-ClMe OMeMe 3-MeH Me OEtEt 3-MeH Me n-C3F7i-Pr 3-MeH Me i-C3F7t-Bu 3-Me5-F Me Etpropargyl 3-MeH Me OCF2CHF2Et 3-MeH Me SCF2CHF2i-Pr 3-MeH Me SO2Met-Bu 3-Me5-ClMe SO2CF3Me 3-MeH CF3CF3Et 3-MeH CF3Mei-Pr 3-MeH OMe CF3t-Bu 3-MeH HCF3cyclopropyl3-Me5-BrHOCHF2Et 3-MeH HC2F5i-Pr 3-Me5-MeHC2F5t-Bu 3-MeH HOCF3Me 3-MeH HOCF2CHF2Et 3-MeH HSCF2CHF2i-Pr 3-Me5-ClHn-C3F7t-Bu 3-MeH Hi-C3F7propargyl 3-MeH HBrEt 3-MeH HCli-Pr 3-MeH HSCF3t-Bu 3-Me5-BrPh CF3cyclopropyl3-MeH Ph ClEt 3-MeH Ph Bri-Pr 3-MeH 2-pyridylCF3t-Bu 3-MeH 2-pyridylClMe 3-MeH 2-ClPh CF3Et 3-Me5-Cl2-ClPh OCF3i-Pr 3-MeH 2-ClPh Brt-Bu 3-MeH 2-ClPh Cl
R3R4aR4bRvaRvbMe 3-MeH 2-ClPh SCHF2propargyl 3-MeH 2-BrPh CF3i-Pr 3-Me5-CN2-MePh CF3t-Bu 3-MeH 2-CNPh CF3Me 3-MeH 2-FPh CF3Et 3-MeH 2，6-F2Ph CF3i-Pr 3-Me5-Br2，4-F2Ph CF3t-Bu 3-MeH 2，5-F2Ph CF3Me 3-Me5-I 2-MeOPhCF3Et 3-MeH 3-Cl-2-pyridyl CF3i-Pr 3-Me5-Me3-Cl-2-pyridyl OCF3t-Bu 3-MeH 3-Cl-2-pyridyl Brpropargyl 3-MeH 3-Cl-2-pyridyl ClEt 3-Me5-Br3-Cl-2-pyridyl SCHF2i-Pr 3-MeH 3-F-2-pyridyl CF3t-Bu 3-MeH 3-CF3-2-pyridyl CF3Me 3-MeH 3-Me-2-pyridyl CF3Et 3-MeH 3-Br-2-pyridyl CF3i-Pr 3-Me5-Cl3-Br-2-pyridyl OCF3t-Bu 3-MeH 3-Br-2-pyridyl Bri-Pr 3-MeH 3-Br-2-pyridyl ClMe 6-MeH H CF3Et 6-Me4-MeH OCF3i-Pr 6-MeH H OCF3t-Bu 6-MeCl Me BrMe 6-MeH Et BrEt 6-MeH Me Cli-Pr 6-Me4-BrEt Clt-Bu 6-MeH Me Ipropargyl 6-MeH Me CF3cyclopropyl6-MeH Me OCF3i-Pr 6-Me4-ClMe CF3t-Bu 6-MeH Me SCF3Me 6-MeH Me SCHF2Et 6-MeH Me OCHF2i-Pr 6-Me4-CNMe CF3
R3R4aR4bRvaRvbt-Bu 6-MeH Me C2F5propargyl 6-MeH Me C2F5cyclopropyl6-MeH Et CF3i-Pr 6-MeH n-Pr CF3t-Bu 6-Me4-Bri-Pr CF3Me 6-MeH Cl CF3Et 6-MeH FCF3i-Pr 6-MeH Me SMet-Bu 6-Me4-ClMe OMeMe 6-MeH Me OEtEt 6-MeH Me n-C3F7i-Pr 6-MeH Me i-C3F7t-Bu 6-Me4-F Me Etpropargyl 6-MeH Me OCF2CHF2Et 6-MeH Me SCF2CHF2i-Pr 6-MeH Me SO2Met-Bu 6-Me4-ClMe SO2CF3Me 6-MeH CF3CF3Et 6-MeH CF3Mei-Pr 6-MeH OMe CF3t-Bu 6-MeH HCF3cyclopropyl6-Me4-BrHOCHF2Et 6-MeH HC2F5i-Pr 6-MeH HC2F5t-Bu 6-Me4-MeHOCF3Me 6-MeH HOCF2CHF2Et 6-MeH HSCF2CHF2i-Pr 6-Me4-ClHn-C3F7t-Bu 6-MeH Hi-C3F7propargyl 6-MeH HBrEt 6-MeH HCli-Pr 6-MeH HSCF3t-Bu 6-Me4-BrPh CF3cyclopropyl6-MeH Ph ClEt 6-MeH Ph Bri-Pr 6-MeH 2-pyridylCF3
R3R4aR4bRvaRvbt-Bu 6-MeH 2-pyridyl ClMe 6-MeH 2-ClPh CF3Et 6-Me4-Cl2-ClPh OCF3i-Pr 6-MeH 2-ClPh Brt-Bu 6-Me4-CN2-ClPh ClMe 6-MeH 2-ClPh SCHF2propargyl 6-MeH 2-BrPh CF3i-Pr 6-MeH 2-MePh CF3t-Bu 6-MeH 2-CNPh CF3Me 6-MeH 2-FPh CF3Et 6-MeH 2，6-F2Ph CF3i-Pr 6-Me4-Br2，4-F2Ph CF3t-Bu 6-MeH 2，5-F2Ph CF3Me 6-Me4-I 2-MeOPhCF3Et 6-MeH 3-Cl-2-pyridyl CF3i-Pr 6-MeH 3-Cl-2-pyridyl OCF3t-Bu 6-MeH 3-Cl-2-pyridyl Brpropargyl 6-MeH 3-Cl-2-pyridyl ClEt 6-Me4-Br3-Cl-2-pyridyl SCHF2i-Pr 6-MeH 3-F-2-pyridyl CF3t-Bu 6-MeH 3-CF3-2-pyridyl CF3Me 6-MeH 3-Me-2-pyridyl CF3Et 6-MeH 3-Br-2-pyridyl CF3i-Pr 6-Me4-Cl3-Br-2-pyridyl OCF3t-Bu 6-MeH 3-Br-2-pyridyl Bri-Pr 6-MeH 3-Br-2-pyridyl ClMe 3-ClH H CF3Et 3-Br5-MeH OCF3i-Pr 3-ClH H OCF3t-Bu 3-Cl5-ClMe BrMe 3-ClH Et BrEt 3-ClH Me Cli-Pr 3-Cl5-BrEt Clt-Bu 3-ClH Me Ipropargyl 3-ClH Me CF3cyclopropyl3-ClH Me OCF3
R3R4aR4bRvaRvbi-Pr 3-Cl5-ClMe CF3t-Bu 3-ClH Me SCF3Me 3-F H Me SCHF2Et 3-ClH Me OCHF2i-Pr 3-Cl5-CNMe CF3t-Bu 3-ClH Me C2F5propargyl 3-ClH Me C2F5cyclopropyl3-ClH Et CF3i-Pr 3-ClH n-PrCF3t-Bu 3-Cl5-Bri-PrCF3Me 3-ClH Cl CF3Et 3-BrH F CF3i-Pr 3-ClH Me SMet-Bu 3-Cl5-ClMe OMeMe 3-ClH Me OEtEt 3-ClH Me n-C3F7i-Pr 3-ClH Me i-C3F7t-Bu 3-Cl5-F Me Etpropargyl 3-ClH Me OCF2CHF2Et 3-ClH Me SCF2CHF2i-Pr 3-BrH Me SO2Met-Bu 3-Cl5-ClMe SO2CF3Me 3-ClH CF3CF3Et 3-CNH CF3Mei-Pr 3-ClH OMe CF3t-Bu 3-ClH H CF3cyclopropyl3-Cl5-BrH OCHF2Et 3-ClH H C2F5i-Pr 3-ClH H C2F5t-Bu 3-ClH H OCF3Me 3-F H H OCF2CHF2Et 3-ClH H SCF2CHF2i-Pr 3-Cl5-ClH n-C3F7t-Bu 3-ClH H i-C3F7propargyl 3-ClH H BrEt 3-ClH H Cl
R3R4aR4bRvaRvbi-Pr 3-ClH H SCF3t-Bu 3-Cl5-BrPhCF3cyclopropyl3-ClH PhClEt 3-ClH PhBri-Pr 3-BrH 2-pyridyl CF3t-Bu 3-ClH 2-pyridyl ClMe 3-ClH 2-ClPhCF3Et 3-Cl5-Cl2-ClPhOCF3i-Pr 3-ClH 2-ClPhBrt-Bu 3-I H 2-ClPhClMe 3-Cl5-Me2-ClPhSCHF2propargyl 3-ClH 2-BrPhCF3i-Pr 3-ClH 2-MePhCF3t-Bu 3-Cl5-CN2-CNPhCF3Me 3-ClH 2-FPh CF3Et 3-ClH 2，6-F2PhCF3i-Pr 3-Cl5-Br2，4-F2PhCF3t-Bu 3-F H 2，5-F2PhCF3Me 3-Cl5-I 2-MeOPh CF3Et 3-ClH 3-Cl-2-pyridylCF3i-Pr 3-CNH 3-Cl-2-pyridylOCF3t-Bu 3-ClH 3-Cl-2-pyridylBrpropargyl 3-ClH 3-Cl-2-pyridylClEt 3-Cl5-Br3-Cl-2-pyridylSCHF2i-Pr 3-ClH 3-F-2-pyridyl CF3t-Bu 3-BrH 3-CF3-2-pyridyl CF3Me 3-ClH 3-Me-2-pyridylCF3Et 3-ClH 3-Br-2-pyridylCF3i-Pr 3-Cl5-Cl3-Br-2-pyridylOCF3t-Bu 3-ClH 3-Br-2-pyridylBri-Pr 3-ClH 3-Br-2-pyridylClMe 6-ClH H CF3Et 6-Br4-MeH OCF3i-Pr 6-ClH H OCF3t-Bu 6-ClCl MeBrMe 6-ClH EtBr
R3R4aR4bRvaRvbEt 6-ClH Me Cli-Pr 6-F 4-BrEt Clt-Bu 6-ClH Me Ipropargyl 6-ClH Me CF3cyclopropyl6-ClH Me OCF3i-Pr 6-Cl4-ClMe CF3t-Bu 6-ClH Me SCF3Me 6-ClH Me SCHF2Et 6-ClH Me OCHF2i-Pr 6-I 4-CNMe CF3t-Bu 6-ClH Me C2F5propargyl 6-ClH Me C2F5cyclopropyl6-ClH Et CF3i-Pr 6-ClH n-PrCF3t-Bu 6-Cl4-Bri-PrCF3Me 6-ClH Cl CF3Et 6-F H F CF3i-Pr 6-ClH Me SMet-Bu 6-Cl4-ClMe OMeMe 6-ClH Me OEtEt 6-I H Me n-C3F7i-Pr 6-ClH Me i-C3F7t-Bu 6-Cl4-F Me Etpropargyl 6-ClH Me OCF2CHF2Et 6-ClH Me SCF2CHF2i-Pr 6-ClH Me SO2Met-Bu 6-Cl4-ClMe SO2CF3Me 6-ClH CF3CF3Et 6-ClH CF3Mei-Pr 6-ClH OMe CF3t-Bu 6-BrH H CF3cyclopropyl6-Cl4-BrH OCHF2Et 6-ClH H C2F5i-Pr 6-ClH H C2F5t-Bu 6-F 4-MeH OCF3Me 6-ClH H OCF2CHF2
R3R4aR4bRvaRvbEt 6-ClH H SCF2CHF2i-Pr 6-CN4-ClH n-C3F7t-bu 6-ClH H i-C3F7propargyl 6-ClH H BrEt 6-ClH H Cli-Pr 6-ClH H SCF3t-Bu 6-Cl4-BrPh CF3cyclopropyl6-ClH Ph ClEt 6-F H Ph Bri-Pr 6-ClH 2-pyridyl CF3t-Bu 6-ClH 2-pyridyl ClMe 6-ClH 2-ClPh CF3Et 6-Br4-Cl2-ClPh OCF3i-Pr 6-ClH 2-ClPh Brt-Bu 6-ClH 2-ClPh ClMe 6-ClH 2-ClPh SCHF2propargyl 6-ClH 2-BrPh CF3i-Pr 6-BrH 2-MePh CF3t-Bu 6-Cl4-CN2-CNPh CF3Me 6-ClH 2-FPh CF3Et 6-ClH 2，6-F2Ph CF3i-Pr 6-Cl4-Br2，4-F2Ph CF3t-Bu 6-CNH 2，5-F2Ph CF3Me 6-Cl4-I 2-MeOPhCF3Et 6-ClH 3-Cl-2-pyridyl CF3i-Pr 6-BrH 3-Cl-2-pyridyl OCF3t-Bu 6-ClH 3-Cl-2-pyridyl Brpropargyl 6-ClH 3-Cl-2-pyridyl ClEt 6-Cl4-Br3-Cl-2-pyridyl SCHF2i-Pr 6-ClH 3-F-2-pyridyl CF3t-Bu 6-ClH 3-CF3-2-pyridyl CF3Me 6-ClH 3-Me-2-pyridyl CF3Et 6-ClH 3-Br-2-pyridyl CF3i-Pr 6-Cl4-Cl3-Br-2-pyridyl OCF3t-Bu 6-ClH 3-Br-2-pyridyl Bri-Pr 6-ClH 3-Br-2-pyridyl Cl
Table 5 R3R4aR4bRvaRvbMe 3-MeH H CF3Et 3-Me5-MeH OCF3i-Pr 3-MeH H OCF3t-Bu 3-Me5-ClMe BrMe 3-MeH Et BrEt 3-MeH Me Cli-Pr 3-Me5-BrEt Clt-Bu 3-MeH Me Ipropargyl 3-MeH Me CF3cyclopropyl3-MeH Me OCF3i-Pr 3-Me5-ClMe CF3t-Bu 3-MeH Me SCF3Me 3-Me5-CNMe SCHF2Et 3-MeH Me OCHF2i-Pr 3-MeH Me CF3t-Bu 3-MeH Me C2F5propargyl 3-MeH Me C2F5cyclopropyl3-MeH Et CF3i-Pr 3-MeH n-PrCF3t-Bu 3-Me5-Bri-PrCF3Me 3-MeH Cl CF3Et 3-MeH F CF3i-Pr 3-MeH Me SMet-Bu 3-Me5-ClMe OMeMe 3-MeH Me OEt
R3R4aR4bRvaRvbEt 3-MeH Me n-C3F7i-Pr 3-MeH Me i-C3F7t-Bu 3-Me5-F Me Etpropargyl 3-MeH Me OCF2CHF2Et 3-MeH Me SCF2CHF2i-Pr 3-MeH Me SO2Met-Bu 3-Me5-ClMe SO2CF3Me 3-MeH CF3CF3Et 3-MeH CF3Mei-Pr 3-MeH OMe CF3t-Bu 3-MeH HCF3cyclopropyl3-Me5-BrHOCHF2Et 3-MeH HC2F5i-Pr 3-Me5-MeHC2F5t-Bu 3-MeH HOCF3Me 3-MeH HOCF2CHF2Et 3-MeH HSCF2CHF2i-Pr 3-Me5-ClHn-C3F7t-Bu 3-MeH Hi-C3F7propargyl 3-MeH HBrEt 3-MeH HCli-Pr 3-MeH HSCF3t-Bu 3-Me5-BrPh CF3cyclopropyl3-MeH Ph ClEt 3-MeH Ph Bri-Pr 3-MeH 2-pyridylCF3t-Bu 3-MeH 2-pyridylClMe 3-MeH 2-ClPh CF3Et 3-Me5-Cl2-ClPh OCF3i-Pr 3-MeH 2-ClPh Brt-Bu 3-MeH 2-ClPh ClMe 3-MeH 2-ClPh SCHF2propargyl 3-MeH 2-BrPh CF3i-Pr 3-Me5-CN2-MePh CF3t-Bu 3-MeH 2-CNPh CF3Me 3-MeH 2-FPhCF3
R3R4aR4bRvaRvbEt 3-MeH 2，6-F2Ph CF3i-Pr 3-Me5-Br2，4-F2Ph CF3t-Bu 3-MeH 2，6-F2Ph CF3Me 3-Me5-I 2-MeOPhCF3Et 3-MeH 3-Cl-2-pyridyl CF3i-Pr 3-Me5-Me3-Cl-2-pyridyl OCF3t-Bu 3-MeH 3-Cl-2-pyridyl Brpropargyl 3-MeH 3-Cl-2-pyridyl ClEt 3-Me5-Br3-Cl-2-pyridyl SCHF2i-Pr 3-MeH 3-F-2-pyridyl CF3t-Bu 3-MeH 3-CF3-2-pyridyl CF3Me 3-MeH 3-Me-2-pyridyl CF3Et 3-MeH 3-Br-2-pyridyl CF3i-Pr 3-Me5-Cl3-Br-2-pyridyl OCF3t-Bu 3-MeH 3-Br-2-pyridyl Bri-Pr 3-MeH 3-Br-2-pyridyl ClMe 6-MeH H CF3Et 6-Me4-MeH OCF3i-Pr 6-MeH H OCF3t-Bu 6-MeCl Me BrMe 6-MeH Et BrEt 6-MeH Me Cli-Pr 6-Me4-BrEt Clt-Bu 6-MeH Me Ipropargyl 6-MeH Me CF3cyclopropyl6-MeH Me OCF3i-Pr 6-Me4-ClMe CF3t-Bu 6-MeH Me SCF3Me 6-MeH Me SCHF2Et 6-MeH Me OCHF2i-Pr 6-Me4-CNMe CF3t-Bu 6-MeH Me C2F5propargyl 6-MeH Me C2F5cyclopropyl6-MeH Et CF3i-Pr 6-MeH n-Pr CF3t-Bu 6-Me4-Bri-Pr CF3
R3R4aR4bRvaRvbMe 6-MeH Cl CF3Et 6-MeH FCF3i-Pr 6-MeH Me SMet-Bu 6-Me4-ClMe OMeMe 6-MeH Me OEtEt 6-MeH Me n-C3F7i-Pr 6-MeH Me i-C3F7t-Bu 6-Me4-F Me Etpropargyl 6-MeH Me OCF2CHF2Et 6-MeH Me SCF2CHF2i-Pr 6-MeH Me SO2Met-Bu 6-Me4-ClMe SO2CF3Me 6-MeH CF3CF3Et 6-MeH CF3Mei-Pr 6-MeH OMe CF3t-Bu 6-MeH HCF3cyclopropyl6-Me4-BrHOCHF2Et 6-MeH HC2F5i-Pr 6-MeH HC2F5t-Bu 6-Me4-MeHOCF3Me 6-MeH HOCF2CHF2Et 6-MeH HSCF2CHF2i-Pr 6-Me4-ClHn-C3F7t-Bu 6-MeH Hi-C3F7propargyl 6-MeH HBrEt 6-MeH HCli-Pr 6-MeH HSCF3t-Bu 6-Me4-BrPh CF3cyclopropyl6-MeH Ph ClEt 6-MeH Ph Bri-Pr 6-MeH 2-pyridylCF3t-Bu 6-MeH 2-pyridylClMe 6-MeH 2-ClPh CF3Et 6-Me4-Cl2-ClPh OCF3i-Pr 6-MeH 2-ClPh Brt-Bu 6-Me4-CN2-ClPh Cl
R3R4aR4bRvaRvbMe 6-MeH 2-ClPh SCHF2propargyl 6-MeH 2-BrPh CF3i-Pr 6-MeH 2-MePh CF3t-Bu 6-MeH 2-CNPh CF3Me 6-MeH 2-FPh CF3Et 6-MeH 2，6-F2Ph CF3i-Pr 6-Me4-Br2，4-F2Ph CF3t-Bu 6-MeH 2，6-F2Ph CF3Me 6-Me4-I 2-MeOPhCF3Et 6-MeH 3-Cl-2-pyridyl CF3i-Pr 6-MeH 3-Cl-2-pyridyl OCF3t-Bu 6-MeH 3-Cl-2-pyridyl Brpropargyl 6-MeH 3-Cl-2-pyridyl ClEt 6-Me4-Br3-Cl-2-pyridyl SCHF2i-Pr 6-MeH 3-F-2-pyridyl CF3t-Bu 6-MeH 3-CF3-2-pyridyl CF3Me 6-MeH 3-Me-2-pyridyl CF3Et 6-MeH 3-Br-2-pyridyl CF3i-Pr 6-Me4-Cl3-Br-2-pyridyl OCF3t-Bu 6-MeH 3-Br-2-pyridyl Bri-Pr 6-MeH 3-Br-2-pyridyl ClMe 3-ClH H CF3Et 3-Br5-MeH OCF3i-Pr 3-ClH H OCF3t-Bu 3-Cl5-ClMe BrMe 3-ClH Et BrEt 3-ClH Me Cli-Pr 3-Cl5-BrEt Clt-Bu 3-ClH Me Ipropargyl 3-ClH Me CF3cyclopropyl3-ClH Me OCF3i-Pr 3-Cl5-ClMe CF3t-Bu 3-ClH Me SCF3Me 3-F H Me SCHF2Et 3-ClH Me OCHF2i-Pr 3-Cl5-CNMe CF3
R3R4aR4bRvaRvbt-Bu 3-ClH Me C2F5propargyl 3-ClH Me C2F5cyclopropyl3-ClH Et CF3i-Pr 3-ClH n-Pr CF3t-Bu 3-Cl5-Bri-Pr CF3Me 3-ClH Cl CF3Et 3-BrH FCF3i-Pr 3-ClH Me SMet-Bu 3-Cl5-ClMe OMeMe 3-ClH Me OEtEt 3-ClH Me n-C3F7i-Pr 3-ClH Me i-C3F7t-Bu 3-Cl5-F Me Etpropargyl 3-ClH Me OCF2CHF2Et 3-ClH Me SCF2CHF2i-Pr 3-BrH Me SO2Met-Bu 3-Cl5-ClMe SO2CF3Me 3-C H CF3CF3Et 3-CNH CF3Mei-Pr 3-ClH OMe CF3t-Bu 3-ClH HCF3cyclopropyl3-Cl5-BrHOCHF2Et 3-ClH HC2F5i-Pr 3-ClH HC2F5t-Bu 3-ClH HOCF3Me 3-F H HOCF2CHF2Et 3-ClH HSCF2CHF2i-Pr 3-Cl5-ClHn-C3F7t-Bu 3-ClH Hi-C3F7propargyl 3-ClH HBrEt 3-ClH HCli-Pr 3-ClH HSCF3t-Bu 3-Cl5-BrPh CF3cyclopropyl3-ClH Ph ClEt 3-ClH Ph Bri-Pr 3-BrH 2-pyridylCF3
R3R4aR4bRvaRvbt-Bu 3-ClH 2-pyridyl ClMe 3-ClH 2-ClPh CF3Et 3-Cl5-Cl2-ClPh OCF3i-Pr 3-ClH 2-ClPh Brt-Bu 3-I H 2-ClPh ClMe 3-Cl5-Me2-ClPh SCHF2propargyl 3-ClH 2-BrPh CF3i-Pr 3-ClH 2-MePh CF3t-Bu 3-Cl5-CN2-CNPh CF3Me 3-ClH 2-FPh CF3Et 3-ClH 2，6-F2Ph CF3i-Pr 3-Cl5-Br2，4-F2Ph CF3t-Bu 3-F H 2，5-F2Ph CF3Me 3-Cl5-I 2-MeOPhCF3Et 3-ClH 3-Cl-2-pyridyl CF3i-Pr 3-CNH 3-Cl-2-pyridyl OCF3t-Bu 3-ClH 3-Cl-2-pyridyl Brpropargyl 3-ClH 3-Cl-2-pyridyl ClEt 3-Cl5-Br3-Cl-2-pyridyl SCHF2i-Pr 3-ClH 3-F-2-pyridyl CF3t-Bu 3-BrH 3-CF3-2-pyridyl CF3Me 3-ClH 3-Me-2-pyridyl CF3Et 3-ClH 3-Br-2-pyridyl CF3i-Pr 3-Cl5-Cl3-Br-2-pyridyl OCF3t-Bu 3-ClH 3-Br-2-pyridyl Bri-Pr 3-ClH 3-Br-2-pyridyl ClMe 6-ClH H CF3Et 6-Br4-MeH OCF3i-Pr 6-ClH H OCF3t-Bu 6-ClCl Me BrMe 6-ClH Et BrEt 6-ClH Me Cli-Pr 6-F 4-BrEt Clt-Bu 6-ClH Me Ipropargyl 6-ClH Me CF3cyclopropyl6-ClH Me OCF3
R3R4aR4bRyaRvbi-Pr 6-Cl4-ClMe CF3t-Bu 6-ClH Me SCF3Me 6-ClH Me SCHF2Et 6-ClH Me OCHF2i-Pr 6-I 4-CNMe CF3t-Bu 6-ClH Me C2F5propargyl 6-ClH Me C2F5cyclopropyl6-ClH Et CF3i-Pr 6-ClH n-PrCF3t-B u6-Cl4-Bri-PrCF3Me 6-ClH Cl CF3Et 6-F H F CF3i-Pr 6-ClH Me SMet-Bu 6-Cl4-ClMe OMeMe 6-ClH Me OEtEt 6-I H Me n-C3F7i-Pr 6-ClH Me i-C3F7t-Bu 6-Cl4-F Me Etpropargyl 6-ClH Me OCF2CHF2Et 6-ClH Me SCF2CHF2i-Pr 6-ClH Me SO2Met-Bu 6-Cl4-ClMe SO2CF3Me 6-ClH CF3CF3Et 6-ClH CF3Mei-Pr 6-ClH OMe CF3t-Bu 6-BrH H CF3cyclopropyl6-Cl4-BrH OCHF2Et 6-ClH H C2F5i-Pr 6-ClH H C2F5t-Bu 6-F 4-MeH OCF3Me 6-ClH H OCF2CHF2Et 6-ClH H SCF2CHF2i-Pr 6-CN4-ClH n-C3F7t-Bu 6-ClH H i-C3F7propargyl 6-ClH H BrEt 6-ClH H Cl
R3R4aR4bRvaRvbi-Pr 6-ClH H SCF3T-Bu 6-Cl4-BrPh CF3cyclopropyl6-ClH Ph ClEt 6-F H Ph Bri-Pr 6-ClH 2-pyridyl CF3t-Bu 6-ClH 2-pyridyl ClMe 6-ClH 2-ClPh CF3Et 6-Br4-Cl2-ClPh OCF3i-Pr 6-ClH 2-ClPh Brt-Bu 6-ClH 2-ClPh ClMe 6-ClH 2-ClPh SCHF2propargyl 6-ClH 2-BrPh CF3i-Pr 6-BrH 2-MePh CF3t-Bu 6-Cl4-CN2-CNPh CF3Me 6-ClH 2-FPh CF3Et 6-ClH 2，6-F2Ph CF3i-Pr 6-Cl4-Br2，4-F2Ph CF3t-Bu 6-CNH 2，6-F2Ph CF3Me 6-Cl4-I 2-MeOPhCF3Et 6-ClH 3-Cl-2-pyridyl CF3i-Pr 6-BrH 3-Cl-2-pyridyl OCF3t-Bu 6-ClH 3-Cl-2-pyridyl Brpropargyl 6-ClH 3-Cl-2-pyridyl ClEt 6-Cl4-Br3-Cl-2-pyridyl SCHF2i-Pr 6-ClH 3-F-2-pyridyl CF3t-Bu 6-ClH 3-CF3-2-pyridyl CF3Me 6-ClH 3-Me-2-pyridyl CF3Et 6-ClH 3-Br-2-pyridyl CF3i-Pr 6-Cl4-Cl3-Br-2-pyridyl OCF3t-Bu 6-ClH 3-Br-2-pyridyl Bri-Pr 6-ClH 3-Br-2-pyridyl Cl
Table 6 R3R4aR4bRvaRvbMe 3-MeH H CF3Et 3-Me5-MeH OCF3i-Pr 3-MeH H OCF3t-Bu 3-Me5-ClMe BrMe 3-MeH Et BrEt 3-MeH Me Cli-Pr 3-Me5-BrEt Clt-Bu 3-MeH Me Ipropargyl 3-MeH Me CF3cyclopropyl3-MeH Me OCF3i-Pr 3-Me5-ClMe CF3t-Bu 3-MeH Me SCF3Me 3-Me5-CNMe SCHF2Et 3-MeH Me OCHF2i-Pr 3-MeH Me CF3t-Bu 3-MeH Me C2F5propargyl 3-MeH Me C2F5cyclopropyl3-MeH Et CF3i-Pr 3-MeH n-PrCF3t-Bu 3-Me5-Bri-PrCF3Me 3-MeH Cl CF3Et 3-MeH F CF3i-Pr 3-MeH Me SMet-Bu 3-Me5-ClMe OMeMe 3-MeH Me OEtEt 3-MeH Me n-C3F7
R3R4aR4bRvaRvbi-Pr 3-MeH Me i-C3F7t-Bu 3-Me5-F Me Etpropargyl 3-MeH Me OCF2CHF2Et 3-MeH Me SCF2CHF2i-Pr 3-MeH Me SO2Met-Bu 3-Me5-ClMe SO2CF3Me 3-MeH CF3CF3Et 3-MeH CF3Mei-Pr 3-MeH OMe CF3t-Bu 3-MeH HCF3cyclopropyl3-Me5-BrHOCHF2Et 3-MeH HC2F5i-Pr 3-Me5-MeHC2F5t-Bu 3-MeH HOCF3Me 3-MeH HOCF2CHF2Et 3-MeH HSCF2CHF2i-Pr 3-Me5-ClHn-C3F7t-Bu 3-MeH Hi-C3F7propargyl 3-MeH HBrEt 3-MeH HCli-Pr 3-MeH HSCF3t-Bu 3-Me5-BrPh CF3cyclopropyl3-MeH Ph ClEt 3-MeH Ph Bri-Pr 3-MeH 2-pyridylCF3t-Bu 3-MeH 2-pyridylClMe 3-MeH 2-ClPh CF3Et 3-Me5-Cl2-ClPh OCF3i-Pr 3-MeH 2-ClPh Brt-Bu 3-MeH 2-ClPh ClMe 3-MeH 2-ClPh SCHF2propargyl 3-MeH 2-BrPh CF3i-Pr 3-Me5-CN2-MePh CF3t-Bu 3-MeH 2-CNPh CF3Me 3-MeH 2-FPhCF3Et 3-MeH 2，6-F2Ph CF3
R3R4aR4bRvaRvbi-Pr 3-Me5-Br2，4-F2Ph CF3t-Bu 3-MeH 2，5-F2Ph CF3Me 3-Me5-I 2-MeOPhCF3Et 3-MeH 3-Cl-2-pyridyl CF3i-Pr 3-Me5-Me3-Cl-2-pyridyl OCF3t-Bu 3-MeH 3-Cl-2-pyridyl Brpropargyl 3-MeH 3-Cl-2-pyridyl ClEt 3-Me5-Br3-Cl-2-pyridyl SCHF2i-Pr 3-MeH 3-F-2-pyridyl CF3t-Bu 3-MeH 3-CF3-2-pyridyl CF3Me 3-MeH 3-Me-2-pyridyl CF3Et 3-MeH 3-Br-2-pyridyl CF3i-Pr 3-Me5-Cl3-Br-2-pyridyl OCF3t-Bu 3-MeH 3-Br--pyridyl Bri-Pr 3-MeH 3-Br-2-pyridyl ClMe 6-MeH H CF3Et 6-Me4-MeH OCF3i-Pr 6-MeH H OCF3t-Bu 6-MeCl Me BrMe 6-MeH Et BrEt 6-MeH Me Cli-Pr 6-Me4-BrEt Clt-Bu 6-MeH Me IproPargyl 6-MeH Me CF3cyclopropyl6-MeH Me OCF3i-Pr 6-Me4-ClMe CF3t-Bu 6-MeH Me SCF3Me 6-MeH Me SCHF2Et 6-MeH Me OCHF2i-Pr 6-Me4-CNMe CF3t-Bu 6-MeH Me C2F5propargyl 6-MeH Me C2F5cyclopropyl6-MeH Et CF3i-Pr 6-MeH n-Pr CF3t-Bu 6-Me4-Bri-Pr CF3Me 6-MeH Cl CF3
R3R4aR4bRvaRvbEt 6-MeH FCF3i-Pr 6-MeH Me SMet-Bu 6-Me4-ClMe OMeMe 6-MeH Me OEtEt 6-MeH Me n-C3F7i-Pr 6-MeH Me i-C3F7t-Bu 6-Me4-F Me Etpropargyl 6-MeH Me OCF2CHF2Et 6-MeH Me SCF2CHF2i-Pr 6-MeH Me SO2Met-Bu 6-Me4-ClMe SO2CF3Me 6-MeH CF3CF3Et 6-MeH CF3Mei-Pr 6-MeH OMe CF3t-Bu 6-MeH HCF3cyclopropyl6-Me4-BrHOCHF2Et 6-MeH HC2F5i-Pr 6-MeH HC2F5t-Bu 6-Me4-MeHOCF3Me 6-MeH HOCF2CHF2Et 6-MeH HSCF2CHF2i-Pr 6-Me4-ClHn-C3F7t-Bu 6-MeH Hi-C3F7Propargyl 6-MeH HBrEt 6-MeH HCli-Pr 6-MeH HSCF3t-Bu 6-Me4-BrPh CF3cyclopropyl6-MeH Ph ClEt 6-MeH Ph Bri-Pr 6-MeH 2-pyridylCF3t-Bu 6-MeH 2-pyridylClMe 6-MeH 2-ClPh CF3Et 6-Me4-Cl2-ClPh OCF3i-Pr 6-MeH 2-ClPh Brt-Bu 6-Me4-CN2-ClPh ClMe 6-MeH 2-ClPh SCHF2
R3R4aR4bRvaRvbpropargyl 6-MeH 2-BrPh CF3i-Pr 6-MeH 2-MePh CF3t-Bu 6-MeH 2-CNPh CF3Me 6-MeH 2-FPh CF3Et 6-MeH 2，6-F2Ph CF3i-Pr 6-Me4-Br2，4-F2Ph CF3t-Bu 6-MeH 2，6-F2Ph CF3Me 6-Me4-I 2-MeOPhCF3Et 6-MeH 3-Cl-2-pyridyl CF3i-Pr 6-MeH 3-Cl-2-pyridyl OCF3t-Bu 6-MeH 3-Cl-2-pyridyl Brpropargyl 6-MeH 3-Cl-2-pyridyl ClEt 6-Me4-Br3-Cl-2-pyridyl SCHF2i-Pr 6-MeH 3-F-2-pyridyl CF3t-Bu 6-MeH 3-CF3-2-pyridyl CF3Me 6-MeH 3-Me-2-pyridyl CF3Et 6-MeH 3-Br-2-pyridyl CF3i-Pr 6-Me4-Cl3-Br-2-pyridyl OCF3t-Bu 6-MeH 3-Br-2-pyridyl Bri-Pr 6-MeH 3-Br-2-pyridyl ClMe 3-ClH H CF3Et 3-Br5-MeH OCF3i-Pr 3-ClH H OCF3t-Bu 3-Cl5-ClMe BrMe 3-ClH Et BrEt 3-ClH Me Cli-Pr 3-Cl5-BrEt Clt-Bu 3-ClH Me Ipropargyl 3-ClH Me CF3cyclopropyl3-ClH Me OCF3i-Pr 3-CL5-ClMe CF3t-Bu 3-ClH Me SCF3Me 3-F H Me SCHF2Et 3-ClH Me OCHF2i-Pr 3-Cl5-CNMe CF3t-Bu 3-ClH Me C2F5
R3R4aR4bRvaRvbpropargyl 3-ClH Me C2F5cyclopropyl3-ClH Et CF3i-Pr 3-ClH n-Pr CF3t-Bu 3-Cl5-Bri-Pr CF3Me 3-ClH Cl CF3Et 3-BrH FCF3i-Pr 3-ClH Me SMet-Bu 3-Cl5-ClMe OMeMe 3-ClH Me OEtEt 3-ClH Me n-C3F7i-Pr 3-ClH Me i-C3F7t-Bu 3-Cl5-F Me Etpropargyl 3-ClH Me OCF2CHF2Et 3-ClH Me SCF2CHF2i-Pr 3-BrH Me SO2Met-Bu 3-Cl5-ClMe SO2CF3Me 3-ClH CF3CF3Et 3-CNH CF3Mei-Pr 3-ClH OMe CF3t-Bu 3-ClH HCF3cyclopropyl3-Cl5-BrHOCHF2Et 3-ClH HC2F5i-Pr 3-ClH HC2F5t-Bu 3-ClH HOCF3Me 3-F H HOCF2CHF2Et 3-ClH HSCF2CHF2i-Pr 3-Cl5-ClHn-C3F7t-Bu 3-ClH Hi-C3F7propargyl 3-ClH HBrEt 3-ClH HCli-Pr 3-ClH HSCF3t-Bu 3-Cl5-BrPh CF3cyclopropyl3-ClH Ph ClEt 3-ClH Ph Bri-Pr 3-BrH 2-pyridylCF3t-Bu 3-ClH 2-pyridylCl
R3R4aR4bRvaRvbMe 3-ClH 2-ClPh CF3Et 3-Cl5-Cl2-ClPh OCF3i-Pr 3-ClH 2-ClPh Brt-Bu 3-I H 2-ClPh ClMe 3-Cl5-Me2-ClPh SCHF2propargyl 3-ClH 2-BrPh CF3i-Pr 3-ClH 2-MePh CF3t-Bu 3-Cl5-CN2-CNPh CF3Me 3-ClH 2-FPh CF3Et 3-ClH 2，6-F2Ph CF3i-Pr 3-Cl5-Br2，4-F2Ph CF3t-Bu 3-F H 2，5-F2Ph CF3Me 3-Cl5-I 2-MeOPhCF3Et 3-ClH 3-Cl-2-pyridyl CF3i-Pr 3-CNH 3-Cl-2-pyridyl OCF3t-Bu 3-ClH 3-Cl-2-pyridyl Brpropargyl 3-ClH 3-Cl-2-pyridyl ClEt 3-Cl5-Br3-Cl-2-pyridyl SCHF2i-Pr 3-ClH 3-F-2-pyridyl CF3t-Bu 3-BrH 3-CF3-2-pyridylCF3Me 3-ClH 3-Me-2-pyridyl CF3Et 3-ClH 3-Br-2-pyridyl CF3i-Pr 3-Cl5-Cl3-Br-2-pyridyl OCF3t-Bu 3-ClH 3-Br-2-pyridyl Bri-Pr 3-ClH 3-Br-2-pyridyl ClMe 6-ClH H CF3Et 6-Br4-MeH OCF3i_Pr 6-ClH H OCF3t-Bu 6-ClCl Me BrMe 6-ClH Et BrEt 6-ClH Me Cli-Pr 6-F 4-BrEt Clt-Bu 6-ClH Me Ipropargyl 6-ClH Me CF3cyclopropyl6-ClH Me OCF3i-Pr 6-Cl4-ClMe CF3
R3R4aR4bRvaRvbt-Bu 6-ClH Me SCF3Me 6-ClH Me SCHF2Et 6-ClH Me OCHF2i-Pr 6-I 4-CNMe CF3t-Bu 6-ClH Me C2F5propargyl 6-ClH Me C2F5cyclopropyl6-ClH Et CF3i-Pr 6-ClH n-PrCF3t-Bu 6-Cl4-Bri-PrCF3Me 6-ClH Cl CF3Et 6-F H F CF3i-Pr 6-ClH Me SMet-Bu 6-Cl4-ClMe OMeMe 6-ClH Me OEtEt 6-I H Me n-C3F7i-Pr 6-ClH Me i-C3F7t-Bu 6-Cl4-F Me Etpropargyl 6-ClH Me OCF2CHF2Et 6-ClH Me SCF2CHF2i-Pr 6-ClH Me SO2Met-Bu 6-Cl4-ClMe SO2CF3Me 6-ClH CF3CF3Et 6-ClH CF3Mei-Pr 6-ClH OMe CF3t-Bu 6-BrH H CF3cyclopropyl6-Cl4-BrH OCHF2Et 6-ClH H C2F5i-Pr 6-ClH H C2F5t-Bu 6-F 4-MeH OCF3Me 6-ClH H OCF2CHF2Et 6-ClH H SCF2CHF2i-Pr 6-CN4-ClH n-C3F7t-Bu 6-ClH H i-C3F7propargyl 6-ClH H BrEt 6-ClH H Cli-Pr 6-ClH H SCF3
R3R4aR4bRvaRvbt-Bu 6-Cl4-BrPh CF3cyclopropyl6-ClH Ph ClEt 6-F H Ph Bri-Pr 6-ClH 2-pyridyl CF3t-Bu 6-ClH 2-pyridyl ClMe 6-ClH 2-ClPh CF3Et 6-Br4-Cl2-ClPh OCF3i-Pr 6-ClH 2-ClPh Brt-Bu 6-ClH 2-ClPh ClMe 6-ClH 2-ClPh SCHF2propargyl 6-ClH 2-BrPh CF3i-Pr 6-BrH 2-MePh CF3t-Bu 6-Cl4-CN2-CNPh CF3Me 6-ClH 2-FPh CF3Et 6-ClH 2，6-F2Ph CF3i-Pr 6-Cl4-Br2，4-F2Ph CF3t-Bu 6-CNH 2，6-F2Ph CF3Me 6-Cl4-I 2-MeOPhCF3Et 6-ClH 3-Cl-2-pyridyl CF3i-Pr 6-BrH 3-Cl-2-pyridyl OCF3t-Bu 6-ClH 3-Cl-2-pyridyl Brpropargyl 6-ClH 3-Cl-2-pyridyl ClEt 6-Cl4-Br3-Cl-2-pyridyl SCHF2i-Pr 6-ClH 3-F-2-pyridyl CF3t-Bu 6-ClH 3-CF3-2-pyridyl CF3Me 6-ClH 3-Me-2-pyridyl CF3Et 6-ClH 3-Br-2-pyridyl CF3i-Pr 6-Cl4-Cl3-Br-2-pyridyl OCF3t-Bu 6-ClH 3-Br-2-pyridyl Bri-Pr 6-ClH 3-Br-2-pyridyl Cl
Table 7 R3R4aR4bRvaRvbMe 3-MeH H CF3Et 3-Me5-MeH OCF3i-Pr 3-MeH H OCF3t-Bu 3-Me5-ClMe BrMe 3-MeH Et BrEt 3-MeH Me Cli-Pr 3-Me5-BrEt Clt-Bu 3-MeH Me Ipropargyl 3-MeH Me CF3cyclopropyl3-MeH Me OCF3i-Pr 3-Me5-ClMe CF3t-Bu 3-MeH Me SCF3Me 3-Me5-CNMe SCHF2Et 3-MeH Me OCHF2i-Pr 3-MeH Me CF3t-Bu 3-MeH Me C2F5propargyl 3-MeH Me C2F5cyclopropyl3-MeH Et CF3i-Pr 3-MeH n-PrCF3t-Bu 3-Me5-Bri-PrCF3Me 3-MeH Cl CF3Et 3-MeH F CF3i-Pr 3-MeH Me SMet-Bu 3-Me5-ClMe OMeMe 3-MeH Me OEtEt 3-MeH Me n-C3F7
R3R4aR4bRvaRvbi-Pr 3-Me H Me i-C3F7t-Bu 3-Me 5-F Me Etpropargyl 3-Me H Me OCF2CHF2Et 3-Me H Me SCF2CHF2i-Pr 3-Me H Me SO2Met-Bu 3-Me 5-ClMe SO2CF3Me 3-Me H CF3CF3Et 3-Me H CF3Mei-Pr 3-Me H OMe CF3t-Bu 3-Me H HCF3cyclopropyl3-Me 5-BrHOCHF2Et 3-Me H HC2F5i-Pr 3-Me 5-MeHC2F5t-Bu 3-Me H HOCF3Me 3-Me H HOCF2CHF2Et 3-Me H HSCF2CHF2i-Pr 3-Me 5-ClHn-C3F7t-Bu 3-Me H Hi-C3F7propargyl 3-Me H HBrEt 3-Me H HCli-Pr 3-Me H HSCF3t-Bu 3-Me 5-BrPh CF3cyclopropyl3-Me H Ph ClEt 3-Me H Ph Bri-Pr 3-Me H 2-pyridylCF3t-Bu 3-Me H 2-pyridylClMe 3-Me H 2-ClPh CF3Et 3-Me 5-Cl2-ClPh OCF3i-Pr 3-Me H 2-ClPh Brt-Bu 3-Me H 2-ClPh ClMe 3-Me H 2-ClPh SCHF2propargyl 3-Me H 2-BrPh CF3i-Pr 3-Me 5-CN2-MePh CF3t-Bu 3-Me H 2-CNPh CF3Me 3-Me H 2-FPhCF3Et 3-Me H 2，6-F2PhCF3
R3R4aR4bRvaRvbi-Pr 3-Me 5-Br 2，4-F2Ph CF3t-Bu 3-Me H 2，5-F2Ph CF3Me 3-Me 5-I 2-MeOPhCF3Et 3-Me H 3-Cl-2-pyridyl CF3i-Pr 3-Me 5-Me 3-Cl-2-pyridyl OCF3t-Bu 3-Me H 3-Cl-2-pyridyl Brpropargyl 3-Me H 3-Cl-2-pyridyl ClEt 3-Me 5-Br 3-Cl-2-pyridyl SCHF2i-Pr 3-Me H 3-F-2-pyridyl CF3t-Bu 3-Me H 3-CF3-2-pyridyl CF3Me 3-Me H 3-Me-2-pyridyl CF3Et 3-Me H 3-Br-2-pyridyl CF3i-Pr 3-Me 5-Cl 3-Br-2-pyridyl OCF3t-Bu 3-Me H 3-Br-2-pyridyl Bri-Pr 3-Me H 3-Br-2-pyridyl ClMe 6-Me H H CF3Et 6-Me 4-Me H OCF3i-Pr 6-Me H H OCF3t-Bu 6-Me ClMe BrMe 6-Me H Et BrEt 6-Me H Me Cli-Pr 6-Me 4-Br Et Clt-Bu 6-Me H Me Ipropargyl 6-Me H Me CF3cyclopropyl6-Me H Me OCF3i-Pr 6-Me 4-Cl Me CF3t-Bu 6-Me H Me SCF3Me 6-Me H Me SCHF2Et 6-Me H Me OCHF2i-Pr 6-Me 4-CN Me CF3t-Bu 6-Me H Me C2F5propargyl 6-Me H Me C2F5cyclopropyl6-Me H Et CF3i-Pr 6-Me H n-Pr CF3t-Bu 6-Me 4-Br i-Pr CF3Me 6-Me H Cl CF3
R3R4aR4bRvaRvbEt 6-Me H FCF3i-Pr 6-Me H Me SMet-Bu 6-Me 4-Cl Me OMeMe 6-Me H Me OEtEt 6-Me H Me n-C3F7i-Pr 6-Me H Me i-C3F7t-Bu 6-Me 4-F Me Etpropargyl 6-Me H Me OCF2CHF2Et 6-Me H Me SCF2CHF2i-Pr 6-Me H Me SO2Met-Bu 6-Me 4-Cl Me SO2CF3Me 6-Me H CF3CF3Et 6-Me H CF3Mei-Pr 6-Me H OMe CF3t-Bu 6-Me H HCF3cyclopropyl6-Me 4-Br HOCHF2Et 6-Me H HC2F5i-Pr 6-Me H HC2F5t-Bu 6-Me 4-Me HOCF3Me 6-Me H HOCF2CHF2Et 6-Me H HSCF2CHF2i-Pr 6-Me 4-Cl Hn-C3F7t-Bu 6-Me H Hi-C3F7propargyl 6-Me H HBrEt 6-Me H HCli-Pr 6-Me H HSCF3t-Bu 6-Me 4-Br Ph CF3cyclopropyl6-Me H Ph ClEt 6-Me H Ph Bri-Pr 6-Me H 2-pyridylCF3t-Bu 6-Me H 2-pyridylClMe 6-Me H 2-ClPh CF3Et 6-Me 4-Cl 2-ClPh OCF3i-Pr 6-Me H 2-ClPh Brt-Bu 6-Me 4-CN 2-ClPh ClMe 6-Me H 2-ClPh SCHF2
R3R4aR4bRvaRvbpropargyl 6-MeH 2-BrPh CF3i-Pr 6-MeH 2-MePh CF3t-Bu 6-MeH 2-CNPh CF3Me 6-MeH 2-FPh CF3Et 6-MeH 2，6-F2Ph CF3i-Pr 6-Me4-Br2，4-F2Ph CF3t-Bu 6-MeH 2，6-F2Ph CF3Me 6-Me4-I 2-MeOPhCF3Et 6-MeH 3-Cl-2-pyridyl CF3i-Pr 6-MeH 3-Cl-2-pyridyl OCF3t-Bu 6-MeH 3-Cl-2-pyridyl Brpropargyl 6-MeH 3-Cl-2-pyridyl ClEt 6-Me4-Br3-Cl-2-pyridyl SCHF2i-Pr 6-MeH 3-F-2-pyridyl CF3t-Bu 6-MeH 3-CF3-2-pyridylCF3Me 6-MeH 3-Me-2-pyridyl CF3Et 6-MeH 3-Br-2-pyridyl CF3i-Pr 6-Me4-Cl3-Br-2-pyridyl OCF3t-Bu 6-MeH 3-Br-2-pyridyl Bri-Pr 6-MeH 3-Br-2-pyridyl ClMe 3-ClH H CF3Et 3-Br5-MeH OCF3i-Pr 3-ClH H OCF3t-Bu 3-Cl5-ClMe BrMe 3-ClH Et BrEt 3-ClH Me Cli-Pr 3-Cl5-BrEt Clt-Bu 3-ClH Me Ipropargyl 3-ClH Me CF3cyclopropyl3-ClH Me OCF3i-Pr 3-Cl5-ClMe CF3t-Bu 3-ClH Me SCF3Me 3-F H Me SCHF2Et 3-ClH Me OCHF2i-Pr 3-Cl5-CNMe CF3t-Bu 3-Cl H Me C2F5
R3R4aR4bRvaRvbpropargyl 3-ClH Me C2F5cyclopropyl3-ClH Et CF3i-Pr 3-ClH n-Pr CF3t-Bu 3-Cl5-Bri-Pr CF3Me 3-ClH Cl CF3Et 3-BrH FCF3i-Pr 3-ClH Me SMet-Bu 3-Cl5-ClMe OMeMe 3-ClH Me OEtEt 3-ClH Me n-C3F7i-Pr 3-ClH Me i-C3F7t-Bu 3-Cl5-F Me Etpropargyl 3-ClH Me OCF2CHF2Et 3-ClH Me SCF2CHF2i-Pr 3-BrH Me SO2Met-Bu 3-Cl5-ClMe SO2CF3Me 3-ClH CF3CF3Et 3-CNH CF3Mei-Pr 3-ClH OMe CF3t-Bu 3-ClH HCF3cyclopropyl3-Cl5-BrHOCHF2Et 3-ClH HC2F5i-Pr 3-ClH HC2F5t-Bu 3-ClH HOCF3Me 3-F H HOCF2CHF2Et 3-ClH HSCF2CHF2i-Pr 3-Cl5-ClHn-C3F7t-Bu 3-ClH Hi-C3F7propargyl 3-ClH HBrEt 3-ClH HCli-Pr 3-ClH HSCF3t-Bu 3-Cl5-BrPh CF3cyclopropyl3-ClH Ph ClEt 3-ClH Ph Bri-Pr 3-BrH 2-pyridylCF3t-Bu 3-ClH 2-pyridylCl
R3R4aR4bRvaRvbMe 3-ClH 2-ClPh CF3Et 3-Cl5-Cl2-ClPh OCF3i-Pr 3-ClH 2-ClPh Brt-Bu 3-I H 2-ClPh ClMe 3-Cl5-Me2-ClPh SCHF2propargyl 3-ClH 2-BrPh CF3i-Pr 3-ClH 2-MePh CF3t-Bu 3-Cl5-CN2-CNPh CF3Me 3-ClH 2-FPh CF3Et 3-ClH 2，6-F2Ph CF3i-Pr 3-Cl5-Br2，4-F2Ph CF3t-Bu 3-F H 2，6-F2Ph CF3Me 3-Cl5-I 2-MeOPhCF3Et 3-ClH 3-Cl-2-pyridyl CF3i-Pr 3-CNH 3-Cl-2-pyridyl OCF3t-Bu 3-ClH 3-Cl-2-pyridyl Brpropargyl 3-ClH 3-Cl-2-pyridyl ClEt 3-Cl5-Br3-Cl-2-pyridyl SCHF2i-Pr 3-ClH 3-F-2-pyridyl CF3t-Bu 3-BrH 3-CF3-2-pyridyl CF3Me 3-ClH 3-Me-2-pyridyl CF3Et 3-ClH 3-Br-2-pyridyl CF3i-Pr 3-Cl5-Cl3-Br-2-pyridyl OCF3t-Bu 3-ClH 3-Br-2-pyridyl Bri-Pr 3-ClH 3-Br-2-pyridyl ClMe 6-ClH H CF3Et 6-Br4-MeH OCF3i-Pr 6-ClH H OCF3t-Bu 6-ClCl Me BrMe 6-ClH Et BrEt 6-ClH Me Cli-Pr 6-F 4-BrEt Clt-Bu 6-ClH Me Ipropargyl 6-ClH Me CF3cyclopropyl6-ClH Me OCF3i-Pr 6-Cl4-ClMe CF3
R3R4aR4bRvaRvbt-Bu 6-ClH Me SCF3Me 6-ClH Me SCHF2Et 6-ClH Me OCHF2i-Pr 6-I 4-CNMe CF3t-Bu 6-ClH Me C2F5propargyl 6-ClH Me C2F5cyclopropyl6-ClH Et CF3i-Pr 6-ClH n-PrCF3t-Bu 6-Cl4-Bri-PrCF3Me 6-ClH Cl CF3Et 6-F H F CF3i-Pr 6-ClH Me SMet-Bu 6-Cl4-ClMe OMeMe 6-ClH Me OEtEt 6-I H Me n-C3F7i-Pr 6-ClH Me i-C3F7t-Bu 6-Cl4-F Me EtproPargyl 6-ClH Me OCF2CHF2Et 6-ClH Me SCF2CHF2i-Pr 6-ClH Me SO2Met-Bu 6-Cl4-ClMe SO2CF3Me 6-ClH CF3CF3Et 6-ClH CF3Mei-Pr 6-ClH OMe CF3t-Bu 6-BrH H CF3cyclopropyl6-Cl4-BrH OCHF2Et 6-ClH H C2F5i-Pr 6-ClH H C2F5t-Bu 6-F 4-MeH OCF3Me 6-ClH H OCF2CHF2Et 6-ClH H SCF2CHF2i-Pr 6-CN4-ClH n-C3F7t-Bu 6-ClH H i-C3F7propargyl 6-ClH H BrEt 6-ClH H Cli-Pr 6-ClH H SCF3
R3R4aR4bRvaRvbt-Bu 6-Cl4-BrPh CF3cyclopropyl6-ClH Ph ClEt 6-F H Ph Bri-Pr 6-ClH 2-pyridyl CF3t-Bu 6-ClH 2-pyridyl ClMe 6-ClH 2-ClPh CF3Et 6-Br4-Cl2-ClPh OCF3i-Pr 6-ClH 2-ClPh Brt-Bu 6-ClH 2-ClPh ClMe 6-ClH 2-ClPh SCHF2propargyl 6-ClH 2-BrPh CF3i-Pr 6-BrH 2-MePh CF3t-Bu 6-Cl4-CN2-CNPh CF3Me 6-ClH 2-FPh CF3Et 6-ClH 2，6-F2Ph CF3i-Pr 6-Cl4-Br2，4-F2Ph CF3t-Bu 6-CNH 2，6-F2Ph CF3Me 6-Cl4-I 2-MeOPhCF3Et 6-ClH 3-Cl-2-pyridyl CF3i-Pr 6-BrH 3-Cl-2-pyridyl OCF3t-Bu 6-ClH 3-Cl-2-pyridyl Brpropargyl 6-ClH 3-Cl-2-pyridyl ClEt 6-Cl4-Br3-Cl-2-pyridyl SCHF2i-Pr 6-ClH 3-F-2-pyridyl CF3t-Bu 6-ClH 3-CF3-2-pyridyl CF3Me 6-ClH 3-Me-2-pyridyl CF3Et 6-ClH 3-Br-2-pyridyl CF3i-Pr 6-Cl4-Cl3-Br-2-pyridyl OCF3t-Bu 6-ClH 3-Br-2-pyridyl Bri-Pr 6-ClH 3-Br-2-pyridyl Cl
Table 8 R3R4aR4bRvaRvbMe 3-Me H H CF3Et 3-Me 5-Me H OCF3i-Pr 3-Me H H OCF3t-Bu 3-Me 5-Cl MeBrMe 3-Me H EtBrEt 3-Me H MeCli-Pr 3-Me 5-Br EtClt-Bu 3-Me H MeIpropargyl 3-Me H MeCF3cyclopropyl3-Me H MeOCF3i-Pr 3-Me 5-Cl MeCF3t-Bu 3-Me H MeSCF3Me 3-Me 5-CN MeSCHF2Et 3-Me H MeOCHF2i-Pr 3-Me H MeCF3t-Bu 3-Me H MeC2F5propargyl 3-Me H MeC2F5cyclopropyl3-Me H EtCF3i-Pr 3-Me H n-Pr CF3t-Bu 3-Me 5-Br i-Pr CF3Me 3-Me H ClCF3Et 3-Me H F CF3i-Pr 3-Me H MeSMet-Bu 3-Me 5-Cl MeOMeMe 3-Me H MeOEtEt 3-Me H Men-C3F7
R3R4aR4bRvaRvbi-Pr 3-MeH Me i-C3F7t-Bu 3-Me5-F Me Etpropargyl 3-MeH Me OCF2CHF2Et 3-MeH Me SCF2CHF2i-Pr 3-MeH Me SO2Met-Bu 3-Me5-ClMe SO2CF3Me 3-MeH CF3CF3Et 3-MeH CF3Mei-Pr 3-MeH OMe CF3t-Bu 3-MeH HCF3cyclopropyl3-Me5-BrHOCHF2Et 3-MeH HC2F5i-Pr 3-Me5-MeHC2F5t-Bu 3-MeH HOCF3Me 3-MeH HOCF2CHF2Et 3-MeH HSCF2CHF2i-Pr 3-Me5-ClHn-C3F7t-Bu 3-MeH Hi-C3F7propargyl 3-MeH HBrEt 3-MeH HCli-Pr 3-MeH HSCF3t-Bu 3-Me5-BrPh CF3cyclopropyl3-MeH Ph ClEt 3-MeH Ph Bri-Pr 3-MeH 2-pyridylCF3t-Bu 3-MeH 2-pyridylClMe 3-MeH 2-ClPh CF3Et 3-Me5-Cl2-ClPh OCF3i-Pr 3-MeH 2-ClPh Brt-Bu 3-MeH 2-ClPh ClMe 3-MeH 2-ClPh SCHF2propargyl 3-MeH 2-BrPh CF3i-Pr 3-Me5-CN2-MePh CF3t-Bu 3-MeH 2-CNPh CF3Me 3-MeH 2-FPhCF3Et 3-MeH 2，6-F2Ph CF3
R3R4aR4bRvaRvbi-Pr 3-Me5-Br2，4-F2Ph CF3t-Bu 3-MeH 2，6-F2Ph CF3Me 3-Me5-I 2-MeOPhCF3Et 3-MeH 3-Cl-2-pyridyl CF3i-Pr 3-Me5-Me3-Cl-2-pyridyl OCF3t-Bu 3-MeH 3-Cl-2-pyridyl Brpropargyl 3-MeH 3-Cl-2-pyridyl ClEt 3-Me5-Br3-Cl-2-pyridyl SCHF2i-Pr 3-MeH 3-F-2-pyridyl CF3t-Bu 3-MeH 3-CF3-2-pyridyl CF3Me 3-MeH 3-Me-2-pyridyl CF3Et 3-MeH 3-Br-2-pyridyl CF3i-Pr 3-Me5-Cl3-Br-2-pyridyl OCF3t-Bu 3-MeH 3-Br-2-pyridyl Bri-Pr 3-MeH 3-Br-2-pyridyl ClMe 6-MeH H CF3Et 6-Me4-MeH OCF3i-Pr 6-MeH H OCF3t-Bu 6-MeCl Me BrMe 6-MeH Et BrEt 6-MeH Me Cli-Pr 6-Me4-BrEt Clt-Bu 6-MeH Me Ipropargyl 6-MeH Me CF3cyclopropyl6-MeH Me OCF3i-Pr 6-Me4-ClMe CF3t-Bu 6-MeH Me SCF3Me 6-MeH Me SCHF2Et 6-MeH Me OCHF2i-Pr 6-Me4-CNMe CF3t-Bu 6-MeH Me C2F5propargyl 6-MeH Me C2F5cyclopropyl6-MeH Et CF3i-Pr 6-MeH n-Pr CF3t-Bu 6-Me4-Bri-Pr CF3Me 6-MeH Cl CF3
R3R4aR4bRvaRvbEt 6-MeH FCF3i-Pr 6-MeH Me SMet-Bu 6-Me4-ClMe OMeMe 6-MeH Me OEtEt 6-MeH Me n-C3F7i-Pr 6-MeH Me i-C3F7t-Bu 6-Me4-F Me Etpropargyl 6-MeH Me OCF2CHF2Et 6-MeH Me SCF2CHF2i-Pr 6-MeH Me SO2Met-Bu 6-Me4-ClMe SO2CF3Me 6-MeH CF3CF3Et 6-MeH CF3Mei-Pr 6-MeH OMe CF3t-Bu 6-MeH HCF3cyclopropyl6-Me4-BrHOCHF2Et 6-MeH HC2F5i-Pr 6-MeH HC2F5t-Bu 6-Me4-MeHOCF3Me 6-MeH HOCF2CHF2Et 6-MeH HSCF2CHF2i-Pr 6-Me4-ClHn-C3F7t-Bu 6-MeH Hi-C3F7propargyl 6-MeH HBrEt 6-MeH HCli-Pr 6-MeH HSCF3t-Bu 6-Me4-BrPh Clcyclopropyl6-MeH Ph ClEt 6-MeH Ph Bri-Pr 6-MeH 2-pyridylCF3t-Bu 6-MeH 2-pyridylClMe 6-MeH 2-ClPh CF3Et 6-Me4-Cl2-ClPh OCF3i-Pr 6-MeH 2-ClPh Brt-Bu 6-Me4-CN2-ClPh ClMe 6-MeH 2-ClPh SCHF2
R3R4aR4bRvaRvbpropargyl 6-MeH 2-BrPh CF3i-Pr 6-MeH 2-MePh CF3t-Bu 6-MeH 2-CNPh CF3Me 6-MeH 2-FPh CF3Et 6-MeH 2，6-F2Ph CF3i-Pr 6-Me4-Br2，4-F2Ph CF3t-Bu 6-MeH 2，6-F2Ph CF3Me 6-Me4-I 2-MeOPhCF3Et 6-MeH 3-Cl-2-pyridyl CF3i-Pr 6-MeH 3-Cl-2-pyridyl OCF3t-Bu 6-MeH 3-Cl-2-pyridyl Brpropargyl 6-MeH 3-Cl-2-pyridyl ClEt 6-Me4-Br3-Cl-2-pyridyl SCHF2i-Pr 6-MeH 3-F-2-pyridyl CF3t-Bu 6-MeH 3-CF3-2-pyridyl CF3Me 6-MeH 3-Me-2-pyridyl CF3Et 6-MeH 3-Br-2-pyridyl CF3i-Pr 6-Me4-Cl3-Br-2-pyridyl OCF3t-Bu 6-MeH 3-Br-2-pyridyl Bri-Pr 6-MeH 3-Br-2-pyridyl ClMe 3-ClH H CF3Et 3-Br5-MeH OCF3i-Pr 3-ClH H OCF3t-Bu 3-Cl5-ClMe BrMe 3-ClH Et BrEt 3-ClH Me Cli-Pr 3-Cl5-BrEt Clt-Br 3-ClH Me Ipropargyl 3-ClH Me CF3cyclopropyl3-ClH Me OCF3i-Pr 3-Cl5-ClMe CF3t-Bu 3-ClH Me SCF3Me 3-F H Me SCHF2Et 3-ClH Me OCHF2i-Pr 3-Cl5-CNMe CF3t-Bu 3-ClH Me C2F5
R3R4aR4bRvaRvbpropargyl 3-Cl H Me C2F5cyclopropyl3-Cl H Et CF3i-Pr 3-Cl H n-Pr CF3t-Bu 3-Cl 5-Bri-Pr CF3Me 3-Cl H Cl CF3Et 3-Br H FCF3i-Pr 3-Cl H Me SMet-Bu 3-Cl 5-ClMe OMeMe 3-Cl H Me OEtEt 3-Cl H Me n-C3F7i-Pr 3-Cl H Me i-C3F7t-Bu 3-Cl 5-F Me Etpropargyl 3-Cl H Me OCF2CHF2Et 3-Cl H Me SCF2CHF2i-Pr 3-Br H Me SO2Mei-Bu 3-Cl 5-ClMe SO2CF3Me 3-Cl H CF3CF3Et 3-CN H CF3Mei-Pr 3-Cl H OMe CF3t-Bu 3-Cl H HCF3cyclopropyl3-Cl 5-BrHOCHF2Et 3-Cl H HC2F5i-Pr 3-Cl H HC2F5t-Bu 3-Cl H HOCF3Me 3-F H HOCF2CHF2Et 3-Cl H HSCF2CHF2i-Pr 3-Cl 5-ClHn-C3F7t-Bu 3-Cl H Hi-C3F7propargyl 3-Cl H HBrEt 3-Cl H HCli-Pr 3-Cl H HSCF3t-Bu 3-Cl 5-BrPh CF3cyclopropyl3-Cl H Ph ClEt 3-Cl H Ph Bri-Pr 3-Br H 2-pyridylCF3t-Bu 3-Cl H 2-pyridylCl
R3R4aR4bRvaRvbMe 3-ClH 2-ClPh CF3Et 3-Cl5-Cl2-ClPh OCF3i-Pr 3-ClH 2-ClPh Brt-Bu 3-I H 2-ClPh ClMe 3-Cl5-Me2-ClPh SCHF2propargyl 3-ClH 2-BrPh CF3i-Pr 3-ClH 2-MePh CF3t-Bu 3-Cl5-CN2-CNPh CF3Me 3-ClH 2-FPh CF3Et 3-ClH 2，6-F2Ph CF3i-Pr 3-Cl5-Br2，4-F2Ph CF3t-Bu 3-F H 2，6-F2Ph CF3Me 3-Cl5-I 2-MeOPhCF3Et 3-ClH 3-Cl-2-pyridyl CF3i-Pr 3-CNH 3-Cl-2-pyridyl OCF3t-Bu 3-ClH 3-Cl-2-pyridyl Brpropargyl 3-ClH 3-Cl-2-pyridyl ClEt 3-Cl5-Br3-Cl-2-pyridyl SCHF2i-Pr 3-ClH 3-F-2-pyridyl CF3t-Bu 3-BrH 3-CF3-2-pyridyl CF3Me 3-ClH 3-Me-2-pyridylCF3Et 3-ClH 3-Br-2-pyridylCF3i-Pr 3-Cl5-Cl3-Br-2-pyridylOCF3t-Bu 3-ClH 3-Br-2-pyridylBri-Pr 3-ClH 3-Br-2-pyridylClMe 6-ClH H CF3Et 6-Br4-MeH OCF3i-Pr 6-ClH H OCF3t-Bu 6-ClCl MeBrMe 6-ClH EtBrEt 6-ClH MeCli-Pr 6-F 4-BrEtClt-Bu 6-ClH MeIpropargyl 6-ClH MeCF3cyclopropyl6-ClH MeOCF3i-Pr 6-Cl4-ClMeCF3
R3R4aR4bRvaRvbt-Bu 6-Cl H MeSCF3Me 6-Cl H MeSCHF2Et 6-Cl H MeOCHF2i-Pr 6-l 4-CN MeCF3t-Bu 6-Cl H MeC2F5propargyl 6-Cl H MeC2F5cyclopropyl6-Cl H EtCF3i-Pr 6-Cl H n-Pr CF3t-Bu 6-Cl 4-Br i-Pr CF3Me 6-Cl H ClCF3Et 6-F H F CF3i-Pr 6-Cl H MeSMet-Bu 6-Cl 4-Cl MeOMeMe 6-Cl H MeOEtEt 6-l H Men-C3F7i-Pr 6-Cl H Mei-C3F7t-Bu 6-Cl 4-F MeEtpropargyl 6-Cl H MeOCF2CHF2Et 6-Cl H MeSCF2CHF2i-Pr 6-Cl H MeSO2Met-Bu 6-Cl 4-Cl MeSO2CF3Me 6-Cl H CF3CF3Et 6-Cl H CF3Mei-Pr 6-Cl H OMe CF3t-Bu 6-Br H H CF3cyclopropyl6-Cl 4-Br H OCHF2Et 6-Cl H H C2F5i-Pr 6-Cl H H C2F5t-Bu 6-F 4-Me H OCF3Me 6-Cl H H OCF2CHF2Et 6-Cl H H SCF2CHF2i-Pr 6-CN 4-Cl H n-C3F7t-Bu 6-Cl H H i-C3F7propargyl 6-Cl H H BrEt 6-Cl H H Cli-Pr 6-Cl H H SCF3
R3R4aR4bRvaRvbt-Bu 6-Cl4-BrPh CF3cyclopropyl6-ClH Ph ClEt 6-F H Ph Bri-Pr 6-ClH 2-pyridyl CF3t-Bu 6-ClH 2-pyridyl ClMe 6-ClH 2-ClPh CF3Et 6-Br4-Cl2-ClPh OCF3i-Pr 6-ClH 2-ClPh Brt-Bu 6-ClH 2-ClPh ClMe 6-ClH 2-ClPh SCHF2propargyl 6-ClH 2-BrPh CF3i-Pr 6-BrH 2-MePh CF3t-Bu 6-Cl4-CN2-CNPh CF3Me 6-ClH 2-FPh CF3Et 6-ClH 2，6-F2Ph CF3i-Pr 6-Cl4-Br2，4-F2Ph CF3t-Bu 6-CNH 2，6-F2Ph CF3Me 6-Cl4-I 2-MeOPhCF3Et 6-ClH 3-Cl-2-pyridyl CF3i-Pr 6-BrH 3-Cl-2-pyridyl OCF3t-Bu 6-ClH 3-Cl-2-pyridyl Brpropargyl 6-ClH 3-Cl-2-pyridyl ClEt 6-Cl4-Br3-Cl-2-pyridyl SCHF2i-Pr 6-ClH 3-F-2-pyridyl CF3t-Bu 6-ClH 3-CF3-2-pyridyl CF3Me 6-ClH 3-Me-2-pyridyl CF3Et 6-ClH 3-Br-2-pyridyl CF3i-Pr 6-Cl4-Cl3-Br-2-pyridyl OCF3t-Bu 6-ClH 3-Br-2-pyridyl Bri-Pr 6-ClH 3-Br-2-pyridyl Cl
Table 9 R3R4aR4bRvaRvbMe 3-Me H H CF3Et 3-Me 5-Me H OCF3i-Pr 3-Me H H OCF3t-Bu 3-Me 5-Cl MeBrMe 3-Me H EtBrEt 3-Me H MeCli-Pr 3-Me 5-Br EtClt-Bu 3-Me H MeIpropargyl 3-Me H MeCF3cyclopropyl3-Me H MeOCF3i-Pr 3-Me 5-Cl MeCF3t-Bu 3-Me H MeSCF3Me 3-Me 5-CN MeSCHF2Et 3-Me H MeOCHF2i-Pr 3-Me H MeCF3t-Bu 3-Me H MeC2F5propargyl 3-Me H MeC2F5cyclopropyl3-Me H EtCF3i-Pr 3-Me H n-Pr CF3t-Bu 3-Me 5-Br i-Pr CF3Me 3-Me H ClCF3Et 3-Me H F CF3i-Pr 3-Me H MeSMet-Bu 3-Me 5-Cl MeOMeMe 3-Me H MeOEtEt 3-Me H Men-C3F7
R3R4aR4bRvaRvbi-Pr 3-MeH Me i-C3F7t-Bu 3-Me5-F Me Etpropargyl 3-MeH Me OCF2CHF2Et 3-MeH Me SCF2CHF2i-Pr 3-MeH Me SO2Met-Bu 3-Me5-ClMe SO2CF3Me 3-MeH CF3CF3Et 3-MeH CF3Mei-Pr 3-MeH OMe CF3t-Bu 3-MeH HCF3cyclopropyl3-Me5-BrHOCHF2Et 3-MeH HC2F5i-Pr 3-Me5-MeHC2F5t-Bu 3-MeH HOCF3Me 3-MeH HOCF2CHF2Et 3-MeH HSCF2CHF2i-Pr 3-Me5-ClHn-C3F7t-Bu 3-MeH Hi-C3F7propargyl 3-MeH HBrEt 3-MeH HCli-Pr 3-MeH HSCF3t-Bu 3-Me5-BrPh CF3cyclopropyl3-MeH Ph ClEt 3-MeH Ph Bri-Pr 3-MeH 2-pyridylCF3t-Bu 3-MeH 2-pyridylClMe 3-MeH 2-ClPh CF3Et 3-Me5-Cl2-ClPh OCF3i-Pr 3-MeH 2-ClPh Brt-Bu 3-MeH 2-ClPh ClMe 3-MeH 2-ClPh SCHF2propargyl 3-MeH 2-BrPh CF3i-Pr 3-Me5-CN2-MePh CF3t-Bu 3-MeH 2-CNPh CF3Me 3-MeH 2-FPhCF3Et 3-MeH 2，6-F2Ph CF3
R3R4aR4bRvaRvbi-Pr 3-Me5-Br2，4-F2Ph CF3t-Bu 3-MeH 2，6-F2Ph CF3Me 3-Me5-I 2-MeOPhCF3Et 3-MeH 3-Cl-2-pyridyl CF3i-Pr 3-Me5-Me3-Cl-2-pyridyl OCF3t-Bu 3-MeH 3-Cl-2-pyridyl Brpropargyl 3-MeH 3-Cl-2-pyridyl ClEt 3-Me5-Br3-Cl-2-pyridyl SCHF2i-Pr 3-MeH 3-F-2-pyridyl CF3t-Bu 3-MeH 3-CF3-2-pyridyl CF3Me 3-MeH 3-Me-2-pyridyl CF3Et 3-MeH 3-Br-2-pyridyl CF3i-Pr 3-Me5-Cl3-Br-2-pyridyl OCF3t-Bu 3-MeH 3-Br-2-pyridyl Bri-Pr 3-MeH 3-Br-2-pyridyl ClMe 6-MeH H CF3Et 6-Me4-MeH OCF3i-Pr 6-MeH H OCF3t-Bu 6-MeCl Me BrMe 6-MeH Et BrEt 6-MeH Me Cli-Pr 6-Me4-BrEt Clt-Bu 6-MeH Me Ipropargyl 6-MeH Me CF3cyclopropyl6-MeH Me OCF3i-Pr 6-Me4-ClMe CF3t-Bu 6-MeH Me SCF3Me 6-MeH Me SCHF2Et 6-MeH Me OCHF2i-Pr 6-Me4-CNMe CF3t-Bu 6-MeH Me C2F5propargyl 6-MeH Me C2F5cyclopropyl6-MeH Et CF3i-Pr 6-MeH n-Pr CF3t-Bu 6-Me4-Bri-Pr CF3Me 6-MeH Cl CF3
R3R4aR4bRvaRvbEt 6-Me H FCF3i-Pr 6-Me H Me SMet-Bu 6-Me 4-ClMe OMeMe 6-Me H Me OEtEt 6-Me H Me n-C3F7i-Pr 6-Me H Me i-C3F7t-Bu 6-Me 4-F Me Etpropargyl 6-Me H Me OCF2CHF2Et 6-Me H Me SCF2CHF2i-Pr 6-Me H Me SO2Met-Bu 6-Me 4-ClMe SO2CF3Me 6-Me H CF3CF3Et 6-Me H CF3Mei-Pr 6-Me H OMe CF3t-Bu 6-Me H HCF3cyclopropyl6-Me 4-BrHOCHF2Et 6-Me H HC2F5i-Pr 6-Me H HC2F5t-Bu 6-Me 4-MeHOCF3Me 6-Me H HOCF2CHF2Et 6-Me H HSCF2CHF2i-Pr 6-Me 4-ClHn-C3F7t-Bu 6-Me H Hi-C3F7propargyl 6-Me H HBrEt 6-Me H HCli-Pr 6-Me H HSCF3t-Bu 6-Me 4-BrPh CF3cyclopropyl6-Me H Ph ClEt 6-Me H Ph Bri-Pr 6-Me H 2-pyridylCF3t-Bu 6-Me H 2-pyridylClMe 6-Me H 2-ClPh CF3Et 6-Me 4-Cl2-ClPh OCF3i-Pr 6-Me H 2-ClPh Brt-Bu 6-Me 4-CN2-ClPh ClMe 6-Me H 2-ClPh SCHF2
R3R4aR4bRvaRvbpropargyl 6-MeH 2-BrPh CF3i-Pr 6-MeH 2-MePh CF3t-Bu 6-MeH 2-CNPh CF3Me 6-MeH 2-FPh CF3Et 6-MeH 2，6-F2Ph CF3i-Pr 6-Me4-Br2，4-F2Ph CF3t-Bu 6-MeH 2，6-F2Ph CF3Me 6-Me4-I 2-MeOPhCF3Et 6-MeH 3-Cl-2-pyridyl CF3i-Pr 6-MeH 3-Cl-2-pyridyl OCF3t-Bu 6-MeH 3-Cl-2-pyridyl Brpropargyl 6-MeH 3-Cl-2-pyridyl ClEt 6-Me4-Br3-Cl-2-pyridyl SCHF2i-Pr 6-MeH 3-F-2-pyridyl CF3t-Bu 6-MeH 3-CF3-2-pyridyl CF3Me 6-MeH 3-Me-2-pyridyl CF3Et 6-MeH 3-Br-2-pyridyl CF3i-Pr 6-Me4-Cl3-Br-2-pyridyl OCF3t-Bu 6-MeH 3-Br-2-pyridyl Bri-Pr 6-MeH 3-Br-2-pyridyl ClMe 3-ClH H CF3Et 3-Br5-MeH OCF3i-Pr 3-ClH H OCF3t-Bu 3-Cl5-ClMe BrMe 3-ClH Et BrEt 3-ClH Me Cli-Pr 3-Cl5-BrEt Clt-Bu 3-ClH Me Ipropargyl 3-ClH Me CF3cyclopropyl3-ClH Me OCF3i-Pr 3-Cl5-ClMe CF3t-Bu 3-ClH Me SCF3Me 3-F H Me SCHF2Et 3-ClH Me OCHF2i-Pr 3-Cl5-CNMe CF3t-Bu 3-ClH Me C2F5
R3R4aR4bRvaRvbpropargyl 3-ClH Me C2F5cyclopropyl3-ClH Et CF3i-Pr 3-ClH n-Pr CF3t-Bu 3-Cl5-Bri-Pr CF3Me 3-ClH Cl CF3Et 3-BrH FCF3i-Pr 3-ClH Me SMet-Bu 3-Cl5-ClMe OMeMe 3-ClH Me OEtEt 3-ClH Me n-C3F7i-Pr 3-ClH Me i-C3F7t-Bu 3-Cl5-F Me Etpropargyl 3-ClH Me OCF2CHF2Et 3-ClH Me SCF2CHF2i-Pr 3-BrH Me SO2Met-Bu 3-Cl5-ClMe SO2CF3Me 3-ClH CF3CF3Et 3-CNH CF3Mei-Pr 3-ClH OMe CF3t-Bu 3-ClH HCF3cyclopropyl3-Cl5-BrHOCHF2Et 3-ClH HC2F5i-Pr 3-ClH HC2F5t-Bu 3-ClH HOCF3Me 3-F H HOCF2CHF2Et 3-ClH HSCF2CHF2i-Pr 3-Cl5-ClHn-C3F7t-Bu 3-ClH Hi-C3F7propargyl 3-ClH HBrEt 3-ClH HCli-Pr 3-ClH HSCF3t-Bu 3-Cl5-BrPh CF3cyclopropyl3-ClH Ph ClEt 3-ClH Ph Bri-Pr 3-BrH 2-pyridylCF3t-Bu 3-ClH 2-pyridylCl
R3R4aR4bRvaRvbMe 3-ClH 2-ClPhCF3Et 3-Cl5-Cl2-ClPhOCF3i-Pr 3-ClH 2-ClPhBrt-Bu 3-I H 2-ClPhClMe 3-Cl5-Me2-ClPhSCHF2propargyl 3-ClH 2-BrPhCF3i-Pr 3-ClH 2-MePhCF3t-Bu 3-Cl5-CN2-CNPhCF3Me 3-ClH 2-FPh CF3Et 3-ClH 2，6-F2PhCF3i-Pr 3-Cl5-Br2，4-F2PhCF3t-Bu 3-F H 2，5-F2PhCF3Me 3-Cl5-I 2-MeOPh CF3Et 3-ClH 3-Cl-2-pyridylCF3i-Pr 3-CNH 3-Cl-2-pyridylOCF3t-Bu 3-ClH 3-Cl-2-pyridylBrpropargyl 3-ClH 3-Cl-2-pyridylClEt 3-Cl5-Br3-Cl-2-pyridylSCHF2i-Pr 3-ClH 3-F-2-pyridyl CF3t-Bu 3-BrH 3-CF3-2-pyridyl CF3Me 3-ClH 3-Me-2-pyridylCF3Et 3-ClH 3-Br-2-pyridylCF3i-Pr 3-Cl5-Cl3-Br-2-pyridylOCF3t-Bu 3-ClH 3-Br-2-pyridylBri-Pr 3-ClH 3-Br-2-pyridylClMe 6-ClH H CF3Et 6-Br4-MeH OCF3i-Pr 6-ClH H OCF3t-Bu 6-ClCl MeBrMe 6-ClH EtBrEt 6-ClH MeCli-Pr 6-F 4-BrEtClt-Bu 6-ClH MeIpropargyl 6-ClH MeCF3cyclopropyl6-ClH MeOCF3i-Pr 6-Cl4-ClMeCF3
R3R4aR4bRvaRvbt-Bu 6-ClH Me SCF3Me 6-ClH Me SCHF2Et 6-ClH Me OCHF2i-Pr 6-I 4-CNMe CF3t-Bu 6-ClH Me C2F5propargyl 6-ClH Me C2F5cyclopropyl6-ClH Et CF3i-Pr 6-ClH n-PrCF3t-Bu 6-Cl4-Bri-PrCF3Me 6-ClH Cl CF3Et 6-F H F CF3i-Pr 6-ClH Me SMet-Bu 6-Cl4-ClMe OMeMe 6-ClH Me OEtEt 6-I H Me n-C3F7i-Pr 6-ClH Me i-C3F7t-Bu 6-Cl4-F Me Etpropargyl 6-ClH Me OCF2CHF2Et 6-ClH Me SCF2CHF2i-Pr 6-ClH Me SO2Met-Bu 6-Cl4-ClMe SO2CF3Me 6-ClH CF3CF3Et 6-ClH CF3Mei-Pr 6-ClH OMe CF3t-Bu 6-BrH H CF3cyclopropyl6-Cl4-BrH OCHF2Et 6-ClH H C2F5i-Pr 6-ClH H C2F5t-Bu 6-F 4-MeH OCF3Me 6-ClH H OCF2CHF2Et 6-ClH H SCF2CHF2i-Pr 6-CN4-ClH n-C3F7t-Bu 6-ClH H i-C3F7propargyl 6-ClH H BrEt 6-ClH H Cli-Pr 6-ClH H SCF3
R3R4aR4bRvaRvbt-Bu 6-Cl4-BrPh CF3cyclopropyl6-ClH Ph ClEt 6-F H Ph Bri-Pr 6-ClH 2-pyridyl CF3t-Bu 6-ClH 2-pyridyl ClMe 6-ClH 2-ClPh CF3Et 6-Br4-Cl2-ClPh OCF3i-Pr 6-ClH 2-ClPh Brt-Bu 6-ClH 2-ClPh ClMe 6-ClH 2-ClPh SCHF2propargyl 6-ClH 2-BrPh CF3i-Pr 6-BrH 2-MePh CF3t-Bu 6-Cl4-CN2-CNPh CF3Me 6-ClH 2-FPh CF3Et 6-ClH 2，6-F2Ph CF3i-Pr 6-Cl4-Br2，4-F2Ph CF3t-Bu 6-CNH 2，6-F2Ph CF3Me 6-Cl4-I 2-MeOPhCF3Et 6-ClH 3-Cl-2-pyridyl CF3i-Pr 6-BrH 3-Cl-2-pyridyl OCF3t-Bu 6-ClH 3-Cl-2-pyridyl Brpropargyl 6-ClH 3-Cl-2-pyridyl ClEt 6-Cl4-Br3-Cl-2-pyridyl SCHF2i-Pr 6-ClH 3-F-2-pyridyl CF3t-Bu 6-ClH 3-CF3-2-pyridyl CF3Me 6-ClH 3-Me-2-pyridyl CF3Et 6-ClH 3-Br-2-pyridyl CF3i-Pr 6-Cl4-Cl3-Br-2-pyridyl OCF3t-Bu 6-ClH 3-Br-2-pyridyl Bri-Pr 6-ClH 3-Br-2-pyridyl Cl
Table 10 R3R4aR4bR5aR5bMe 3-Me H H CF3Et 3-Me 5-Me H OCF3i-Pr 3-Me H H OCF3t-Bu 3-Me 5-Cl MeBrMe 3-Me H EtBrEt 3-Me H MeCli-Pr 3-Me 5-Br EtClt-Bu 3-Me H MeIpropargyl 3-Me H MeCF3cyclopropyl3-Me H MeOCF3i-Pr 3-Me 5-Cl MeCF3t-Bu 3-Me H MeSCF3Me 3-Me 5-CN MeSCHF2Et 3-Me H MeOCHF2i-Pr 3-Me H MeCF3t-Bu 3-Me H MeC2F5propargyl 3-Me H MeC2F5cyclopropyl3-Me H EtCF3i-Pr 3-Me H n-Pr CF3t-Bu 3-Me 5-Br i-Pr CF3Me 3-Me H ClCF3Et 3-Me H F CF3i-Pr 3-Me H MeSMet-Bu 3-Me 5-Cl MeOMeMe 3-Me H MeOEtEt 3-Me H Men-C3F7
R3R4aR4bR5aR5bi-Pr 3-MeH Me i-C3F7t-Bu 3-Me5-F Me Etpropargyl 3-MeH Me OCF2CHF2Et 3-MeH Me SCF2CHF2i-Pr 3-MeH Me SO2Met-Bu 3-Me5-ClMe SO2CF3Me 3-MeH CF3CF3Et 3-MeH CF3Mei-Pr 3-MeH OMe CF3t-Bu 3-MeH HCF3cyclopropyl3-Me5-BrHOCHF2Et 3-MeH HC2F5i-Pr 3-Me5-MeHC2F5t-Bu 3-MeH HOCF3Me 3-MeH HOCF2CHF2Et 3-MeH HSCF2CHF2i-Pr 3-Me5-ClHn-C3F7t-Bu 3-MeH Hi-C3F7propargyl 3-MeH HBrEt 3-MeH HCli-Pr 3-MeH HSCF3t-Bu 3-Me5-BrPh CF3cyclopropyl3-MeH Ph ClEt 3-MeH Ph Bri-Pr 3-MeH 2-pyridylCF3t-Bu 3-MeH 2-pyridylClMe 3-MeH 2-ClPh CF3Et 3-Me5-Cl2-ClPh OCF3i-Pr 3-MeH 2-ClPh Brt-Bu 3-MeH 2-ClPh ClMe 3-MeH 2-ClPh SCHF2propargyl 3-MeH 2-BrPh CF3i-Pr 3-Me5-CN2-MePh CF3t-Bu 3-MeH 2-CNPh CF3Me 3-MeH 2-FPhCF3Et 3-MeH 2，6-F2Ph CF3
R3R4aR4bR5aR5bi-Pr 3-Me5-Br2，4-F2Ph CF3t-Bu 3-MeH 2，5-F2Ph CF3Me 3-Me5-I 2-MeOPhCF3Et 3-MeH 3-Cl-2-pyridyl CF3i-Pr 3-Me5-Me3-Cl-2-pyridyl OCF3t-Bu 3-MeH 3-Cl-2-pyridyl Brpropargyl 3-MeH 3-Cl-2-pyridyl ClEt 3-Me5-Br3-Cl-2-pyridyl SCHF2i-Pr 3-MeH 3-F-2-pyridyl CF3t-Bu 3-MeH 3-CF3-2-pyridyl CF3Me 3-MeH 3-Me-2-pyridyl CF3Et 3-MeH 3-Br-2-pyridyl CF3i-Pr 3-Me5-Cl3-Br-2-pyridyl OCF3t-Bu 3-MeH 3-Br-2-pyridyl Bri-Pr 3-MeH 3-Br-2-pyridyl ClMe 6-MeH H CF3Et 6-Me4-MeH OCF3i-Pr 6-MeH H OCF3t-Bu 6-MeCl Me BrMe 6-MeH Et BrEt 6-MeH Me Cli-Pr 6-Me4-BrEt Clt-Bu 6-MeH Me Ipropargyl 6-MeH Me CF3cyclopropyl6-MeH Me OCF3i-Pr 6-Me4-ClMe CF3t-Bu 6-MeH Me SCF3Me 6-MeH Me SCHF2Et 6-MeH Me OCHF2i-Pr 6-Me4-CNMe CF3t-Bu 6-MeH Me C2F5propargyl 6-MeH Me C2F5cyclopropyl6-MeH Et CF3i-Pr 6-MeH n-Pr CF3t-Bu 6-Me4-Bri-Pr CF3Me 6-MeH Cl CF3
R3R4aR4bR5aR5bEt 6-MeH FCF3i-Pr 6-MeH Me SMet-Bu 6-Me4-ClMe OMeMe 6-MeH Me OEtEt 6-MeH Me n-C3F7i-Pr 6-MeH Me i-C3F7t-Bu 6-Me4-F Me Etpropargyl 6-MeH Me OCF2CHF2Et 6-MeH Me SCF2CHF2i-Pr 6-MeH Me SO2Met-Bu 6-Me4-ClMe SO2CF3Me 6-MeH CF3CF3Et 6-MeH CF3Mei-Pr 6-MeH OMe CF3t-Bu 6-MeH HCF3cyclopropyl6-Me4-BrHOCHF2Et 6-MeH HC2F5i-Pr 6-MeH HC2F5t-Bu 6-Me4-MeHOCF3Me 6-MeH HOCF2CHF2Et 6-MeH HSCF2CHF2i-Pr 6-Me4-ClHn-C3F7t-Bu 6-MeH Hi-C3F7propargyl 6-MeH HBrEt 6-MeH HCli-Pr 6-MeH HSCF3i-Bu 6-Me4-BrPh CF3cyclopropyl6-MeH Ph ClEt 6-MeH Ph Bri-Pr 6-MeH 2-pyridylCF3t-Bu 6-MeH 2-pyridylClMe 6-MeH 2-ClPh CF3Et 6-Me4-Cl2-ClPh OCF3i-Pr 6-MeH 2-ClPh Brt-Bu 6-Me4-CN2-ClPh ClMe 6-MeH 2-ClPh SCHF2
R3R4aR4bR5aR5bpropargyl 6-MeH 2-BrPh CF3i-Pr 6-MeH 2-MePh CF3t-Bu 6-MeH 2-CNPh CF3Me 6-MeH 2-FPh CF3Et 6-MeH 2，6-F2Ph CF3i-Pr 6-Me4-Br2，4-F2Ph CF3t-Bu 6-MeH 2，6-F2Ph CF3Me 6-Me4-I 2-MeOPhCF3Et 6-MeH 3-Cl-2-pyridyl CF3i-Pr 6-MeH 3-Cl-2-pyridyl OCF3t-Bu 6-MeH 3-Cl-2-pyridyl Brpropargyl 6-MeH 3-Cl-2-pyridyl ClEt 6-Me4-Br3-Cl-2-pyridyl SCHF2i-Pr 6-MeH 3-F-2-pyridyl CF3t-Bu 6-MeH 3-CF3-2-pyridyl CF3Me 6-MeH 3-Me-2-pyridyl CF3Et 6-MeH 3-Br-2-pyridyl CF3i-Pr 6-Me4-Cl3-Br-2-pyridyl OCF3t-Bu 6-MeH 3-Br-2-pyridyl Bri-Pr 6-MeH 3-Br-2-pyridyl ClMe 3-ClH H CF3Et 3-Br5-MeH OCF3i-Pr 3-ClH H OCF3t-Bu 3-Cl5-ClMe BrMe 3-ClH Et BrEt 3-ClH Me Cli-Pr 3-Cl5-BrEt Clt-Bu 3-ClH Me Ipropargyl 3-ClH Me CF3cyclopropyl3-ClH Me OCF3i-Pr 3-Cl5-ClMe CF3t-Bu 3-ClH Me SCF3Me 3-F H Me SCHF2Et 3-ClH Me OCHF2i-Pr 3-Cl5-CNMe CF3t-Bu 3-ClH Me C2F5
R3R4aR4bR5aR5bpropargyl 3-ClH Me C2F5cyclopropyl3-ClH Et CF3i-Pr 3-ClH n-Pr CF3t-Bu 3-Cl5-Bri-Pr CF3Me 3-ClH Cl CF3Et 3-BrH FCF3i-Pr 3-ClH Me SMet-Bu 3-Cl5-ClMe OMeMe 3-ClH Me OEtEt 3-ClH Me n-C3F7i-Pr 3-ClH Me i-C3F7t-Bu 3-Cl5-F Me Etpropargyl 3-ClH Me OCF2CHF2Et 3-ClH Me SCF2CHF2i-Pr 3-BrH Me SO2Met-Bu 3-Cl5-ClMe SO2CF3Me 3-ClH CF3CF3Et 3-CNH CF3Mei-Pr 3-ClH OMe CF3t-Bu 3-ClH HCF3cycloPropyl3-Cl5-BrHOCHF2Et 3-ClH HC2F5i-Pr 3-ClH HC2F5t-Bu 3-ClH HOCF3Me 3-F H HOCF2CHF2Et 3-ClH HSCF2CHF2i-Pr 3-Cl5-ClHn-C3F7t-Bu 3-ClH Hi-C3F7propargyl 3-ClH HBrEt 3-ClH HCli-Pr 3-ClH HSCF3t-Bu 3-Cl5-BrPh CF3cyclopropyl3-ClH Ph ClEt 3-ClH Ph Bri-Pr 3-BrH 2-pyridylCF3t-Bu 3-ClH 2-pyridylCl
R3R4aR4bR5aR5bMe 3-ClH 2-ClPh CF3Et 3-Cl5-Cl2-ClPh OCF3i-Pr 3-ClH 2-ClPh Brt-Bu 3-I H 2-ClPh ClMe 3-Cl5-Me2-ClPh SCHF2propargyl 3-ClH 2-BrPh CF3i-Pr 3-ClH 2-MePh CF3t-Bu 3-Cl5-CN2-CNPh CF3Me 3-ClH 2-FPh CF3Et 3-ClH 2，6-F2Ph CF3i-Pr 3-Cl5-Br2，4-F2Ph CF3t-Bu 3-F H 2，5-F2Ph CF3Me 3-Cl5-I 2-MeOPhCF3Et 3-ClH 3-Cl-2-pyridyl CF3i-Pr 3-CNH 3-Cl-2-pyridyl OCF3t-Bu 3-ClH 3-Cl-2-pyridyl Brpropargyl 3-ClH 3-Cl-2-pyridyl ClEt 3-Cl5-Br3-Cl-2-pyridyl SCHF2i-Pr 3-ClH 3-F-2-pyridyl CF3t-Bu 3-BrH 3-CF3-2-pyridyl CF3Me 3-ClH 3-Me-2-pyridyl CF3Et 3-ClH 3-Br-2-pyridyl CF3i-Pr 3-Cl5-Cl3-Br-2-Pyridyl OCF3t-Bu 3-ClH 3-Br-2-pyridyl Bri-Pr 3-ClH 3-Br-2-pyridyl ClMe 6-ClH H CF3Et 6-Br4-MeH OCF3i-Pr 6-ClH H OCF3t-Bu 6-ClCl Me BrMe 6-ClH Et BrEt 6-ClH Me Cli-Pr 6-F 4-BrEt Clt-Bu 6-ClH Me Ipropargyl 6-ClH Me CF3cyclopropyl6-ClH Me OCF3i-Pr 6-Cl4-ClMe CF3
R3R4aR4bR5aR5bt-Bu 6-Cl H MeSCF3Me 6-Cl H MeSCHF2Et 6-Cl H MeOCHF2i-Pr 6-I 4-CN MeCF3t-Bu 6-Cl H MeC2F5propargyl 6-Cl H MeC2F5cyclopropyl6-Cl H EtCF3i-Pr 6-Cl H n-Pr CF3t-Bu 6-Cl 4-Br i-Pr CF3Me 6-Cl H ClCF3Et 6-F H F CF3i-Pr 6-Cl H MeSMet-Bu 6-Cl 4-Cl MeOMeMe 6-Cl H MeOEtEt 6-I H Men-C3F7i-Pr 6-Cl H Mei-C3F7t-Bu 6-Cl 4-F MeEtpropargyl 6-Cl H MeOCF2CHF2Et 6-Cl H MeSCF2CHF2i-Pr 6-Cl H MeSO2Met-Bu 6-Cl 4-Cl MeSO2CF3Me 6-Cl H CF3CF3Et 6-Cl H CF3Mei-Pr 6-Cl H OMe CF3t-Bu 6-Br H H CF3cyclopropyl6-Cl 4-Br H OCHF2Et 6-Cl H H C2F5i-Pr 6-Cl H H C2F5t-Bu 6-F 4-Me H OCF3Me 6-Cl H H OCF2CHF2Et 6-Cl H H SCF2CHF2i-Pr 6-CN 4-Cl H n-C3F7t-Bu 6-Cl H H i-C3F7propargyl 6-Cl H H BrEt 6-Cl H H Cli-Pr 6-Cl H H SCF3
R3R4aR4bR5aR5bt-Bu 6-Cl4-BrPh CF3cyclopropyl6-ClH Ph ClEt 6-F H Ph Bri-Pr 6-ClH 2-pyridyl CF3t-Bu 6-ClH 2-pyridyl ClMe 6-ClH 2-ClPh CF3Et 6-Br4-Cl2-ClPh OCF3i-Pr 6-ClH 2-ClPh Brt-Bu 6-ClH 2-ClPh ClMe 6-ClH 2-ClPh SCHF2propargyl 6-ClH 2-BrPh CF3i-Pr 6-BrH 2-MePh CF3t-Bu 6-Cl4-CN2-CNPh CF3Me 6-ClH 2-FPh CF3Et 6-ClH 2，6-F2Ph CF3i-Pr 6-Cl4-Br2，4-F2Ph CF3t-Bu 6-CNH 2，6-F2Ph CF3Me 6-Cl4-I 2-MeOPhCF3Et 6-ClH 3-Cl-2-pyridyl CF3i-Pr 6-BrH 3-Cl-2-pyridyl OCF3t-Bu 6-ClH 3-Cl-2-pyridyl Brpropargyl 6-ClH 3-Cl-2-pyridyl ClEt 6-Cl4-Br3-Cl-2-pyridyl SCHF2i-Pr 6-ClH 3-F-2-pyridyl CF3t-Bu 6-ClH 3-CF3-2-pyridyl CF3Me 6-ClH 3-Me-2-pyridyl CF3Et 6-ClH 3-Br-2-pyridyl CF3i-Pr 6-Cl4-Cl3-Br-2-pyridyl OCF3t-Bu 6-ClH 3-Br-2-pyridyl Bri-Pr 6-ClH 3-Br-2-pyridyl Cl
Table 11 R3R4aR4bRvaRvbMe 3-Me H H CF3Et 3-Me 5-Me H OCF3i-Pr 3-Me H H OCF3t-Bu 3-Me 5-Cl MeBrMe 3-Me H EtBrEt 3-Me H MeCli-Pr 3-Me 5-Br EtClt-Bu 3-Me H MeIpropargyl 3-Me H MeCF3cyclopropyl3-Me H MeOCF3i-Pr 3-Me 5-Cl MeCF3t-Bu 3-Me H MeSCF3Me 3-Me 5-CN MeSCHF2Et 3-Me H MeOCHF2i-Pr 3-Me H MeCF3t-Bu 3-Me H MeC2F5propargyl 3-Me H MeC2F5cyclopropyl3-Me H EtCF3i-Pr 3-Me H n-Pr CF3t-Bu 3-Me 5-Br i-Pr CF3Me 3-Me H ClCF3Et 3-Me H F CF3i-Pr 3-Me H MeSMet-Bu 3-Me 5-Cl MeOMeMe 3-Me H MeOEtEt 3-Me H Men-C3F7
R3R4aR4bRvaRvbi-Pr 3-MeH Me i-C3F7t-Bu 3-Me5-F Me Etpropargyl 3-MeH Me OCF2CHF2Et 3-MeH Me SCF2CHF2i-Pr 3-MeH Me SO2Met-Bu 3-Me5-ClMe SO2CF3Me 3-MeH CF3CF3Et 3-MeH CF3Mei-Pr 3-MeH OMe CF3t-Bu 3-MeH HCF3cyclopropyl3-Me5-BrHOCHF2Et 3-MeH HC2F5i-Pr 3-Me5-MeHC2F5t-Bu 3-MeH HOCF3Me 3-MeH HOCF2CHF2Et 3-MeH HSCF2CHF2i-Pr 3-Me5-ClHn-C3F7t-Bu 3-MeH Hi-C3F7propargyl 3-MeH HBrEt 3-MeH HCli-Pr 3-MeH HSCF3t-Bu 3-Me5-BrPh CF3cyclopropyl3-MeH Ph ClEt 3-MeH Ph Bri-Pr 3-MeH 2-pyridylCF3t-Bu 3-MeH 2-pyridylClMe 3-MeH 2-ClPh CF3Et 3-Me5-Cl2-ClPh OCF3i-Pr 3-MeH 2-ClPh Brt-Bu 3-MeH 2-ClPh ClMe 3-MeH 2-ClPh SCHF2propargyl 3-MeH 2-BrPh CF3i-Pr 3-Me5-CN2-MePh CF3t-Bu 3-MeH 2-CNPh CF3Me 3-MeH 2-FPhCF3Et 3-MeH 2，6-F2Ph CF3
R3R4aR4bRvaRvbi-Pr 3-Me5-Br2，4-F2Ph CF3t-Bu 3-MeH 2，5-F2Ph CF3Me 3-Me5-I 2-MeOPhCF3Et 3-MeH 3-Cl-2-pyridyl CF3i-Pr 3-Me5-Me3-Cl-2-pyridyl OCF3t-Bu 3-MeH 3-Cl-2-pyridyl Brpropargyl 3-MeH 3-Cl-2-pyridyl ClEt 3-Me5-Br3-Cl-2-pyridyl SCHF2i-Pr 3-MeH 3-F-2-pyridyl CF3t-Bu 3-MeH 3-CF3-2-pyridyl CF3Me 3-MeH 3-Me-2-pyridyl CF3Et 3-MeH 3-Br-2-pyridyl CF3i-Pr 3-Me5-Cl3-Br-2-pyridyl OCF3t-Bu 3-MeH 3-Br-2-pyridyl Bri-Pr 3-MeH 3-Br-2-pyridyl ClMe 6-MeH H CF3Et 6-Me4-MeH OCF3i-Pr 6-MeH H OCF3t-Bu 6-MeCl Me BrMe 6-MeH Et BrEt 6-MeH Me Cli-Pr 6-Me4-BrEt Clt-Bu 6-MeH Me Ipropargyl 6-MeH Me CF3cyclopropyl6-MeH Me OCF3i-Pr 6-Me4-ClMe CF3t-Bu 6-MeH Me SCF3Me 6-MeH Me SCHF2Et 6-MeH Me OCHF2i-Pr 6-Me4-CNMe CF3t-Bu 6-MeH Me C2F5propargyl 6-MeH Me C2F5cyclopropyl6-MeH Et CF3i-Pr 6-MeH n-Pr CF3t-Bu 6-Me4-Bri-Pr CF3Me 6-MeH Cl CF3
R3R4aR4bRvaRvbEt 6-MeH FCF3i-Pr 6-MeH Me SMet-Bu 6-Me4-ClMe OMeMe 6-MeH Me OEtEt 6-MeH Me n-C3F7i-Pr 6-MeH Me i-C3F7t-Bu 6-Me4-F Me Etpropargyl 6-MeH Me OCF2CHF2Et 6-MeH Me SCF2CHF2i-Pr 6-MeH Me SO2Met-Bu 6-Me4-ClMe SO2CF3Me 6-MeH CF3CF3Et 6-MeH CF3Mei-Pr 6-MeH OMe CF3t-Bu 6-MeH HCF3cyclopropyl6-Me4-BrHOCHF2Et 6-MeH HC2F5i-Pr 6-MeH HC2F5t-Bu 6-Me4-MeHOCF3Me 6-MeH HOCF2CHF2Et 6-MeH HSCF2CHF2i-Pr 6-Me4-ClHn-C3F7t-Bu 6-MeH Hi-C3F7propargyl 6-MeH HBrEt 6-MeH HCli-Pr 6-MeH HSCF3t-Bu 6-Me4-BrPh CF3cyclopropyl6-MeH Ph ClEt 6-MeH Ph Bri-Pr 6-MeH 2-pyridylCF3t-Bu 6-MeH 2-pyridylClMe 6-MeH 2-ClPh CF3Et 6-Me4-Cl2-ClPh OCF3i-Pr 6-MeH 2-ClPh Brt-Bu 6-Me4-CN2-ClPh ClMe 6-MeH 2-ClPh SCHF2
R3R4aR4bRvaRvbpropargyl 6-MeH 2-BrPh CF3i-Pr 6-MeH 2-MePh CF3t-Bu 6-MeH 2-CNPh CF3Me 6-MeH 2-FPh CF3Et 6-MeH 2，6-F2Ph CF3i-Pr 6-Me4-Br2，4-F2Ph CF3t-Bu 6-MeH 2，6-F2Ph CF3Me 6-Me4-I 2-MeOPhCF3Et 6-MeH 3-Cl-2-pyridyl CF3i-Pr 6-MeH 3-Cl-2-pyridyl OCF3t-Bu 6-MeH 3-Cl-2-pyridyl Brpropargyl 6-MeH 3-Cl-2-pyridyl ClEt 6-Me4-Br3-Cl-2-pyridyl SCHF2i-Pr 6-MeH 3-F-2-pyridyl CF3t-Bu 6-MeH 3-CF3-2-pyridyl CF3Me 6-MeH 3-Me-2-pyridyl CF3Et 6-MeH 3-Br-2-pyridyl CF3i-Pr 6-Me4-Cl3-Br-2-pyridyl OCF3t-Bu 6-MeH 3-Br-2-pyridyl Bri-Pr 6-MeH 3-Br-2-pyridyl ClMe 3-ClH H CF3Et 3-Br5-MeH OCF3i-Pr 3-ClH H OCF3t-Bu 3-Cl5-ClMe BrMe 3-ClH Et BrEt 3-ClH Me Cli-Pr 3-Cl5-BrEt Clt-Bu 3-ClH Me Ipropargyl 3-ClH Me CF3cyclopropyl3-ClH Me OCF3i-Pr 3-Cl5-ClMe CF3t-Bu 3-ClH Me SCF3Me 3-F H Me SCHF2Et 3-ClH Me OCHF2i-Pr 3-Cl5-CNMe CF3t-Bu 3-ClH Me C2F5
R3R4aR4bRvaRvbpropargyl 3-ClH Me C2F5cyclopropyl3-ClH Et CF3i-Pr 3-ClH n-Pr CF3t-Bu 3-Cl5-Bri-Pr CF3Me 3-ClH Cl CF3Et 3-BrH FCF3i-Pr 3-ClH Me SMet-Bu 3-Cl5-ClMe OMeMe 3-ClH Me OEtEt 3-ClH Me n-C3F7i-Pr 3-ClH Me i-C3F7t-Bu 3-Cl5-F Me Etpropargyl 3-ClH Me OCF2CHF2Et 3-ClH Me SCF2CHF2i-Pr 3-BrH Me SO2Met-Bu 3-Cl5-ClMe SO2CF3Me 3-ClH CF3CF3Et 3-CNH CF3Mei-Pr 3-ClH OMe CF3t-Bu 3-ClH HCF3cyclopropyl3-Cl5-BrHOCHF2Et 3-ClH HC2F5i-Pr 3-ClH HC2F5t-Bu 3-ClH HOCF3Me 3-F H HOCF2CHF2Et 3-ClH HSCF2CHF2i-Pr 3-Cl5-ClHn-C3F7t-Bu 3-ClH Hi-C3F7propargyl 3-ClH HBrEt 3-ClH HCli-Pr 3-ClH HSCF3t-Bu 3-Cl5-BrPh CF3cyclopropyl3-ClH Ph ClEt 3-ClH Ph Bri-Pr 3-BrH 2-pyridylCF3t-Bu 3-ClH 2-pyridylCl
R3R4aR4bRvaRvbMe 3-ClH 2-ClPh CF3Et 3-Cl5-Cl2-ClPh OCF3i-Pr 3-ClH 2-ClPh Brt-Bu 3-I H 2-ClPh ClMe 3-Cl5-Me2-ClPh SCHF2propargyl 3-ClH 2-BrPh CF3i-Pr 3-ClH 2-MePh CF3t-Bu 3-Cl5-CN2-CNPh CF3Me 3-ClH 2-FPh CF3Et 3-ClH 2，6-F2Ph CF3i-Pr 3-Cl5-Br2，4-F2Ph CF3t-Bu 3-F H 2，6-F2Ph CF3Me 3-Cl5-I 2-MeOPhCF3Et 3-ClH 3-Cl-2-pyridyl CF3i-Pr 3-CNH 3-Cl-2-pyridyl OCF3t-Bu 3-ClH 3-Cl-2-pyridyl Brpropargyl 3-ClH 3-Cl-2-pyridyl ClEt 3-Cl5-Br3-Cl-2-pyridyl SCHF2i-Pr 3-ClH 3-F-2-pyridyl CF3t-Bu 3-BrH 3-CF3-2-pyridyl CF3Me 3-ClH 3-Me-2-pyridyl CF3Et 3-ClH 3-Br-2-pyridyl CF3i-Pr 3-Cl5-Cl3-Br-2-pyridyl OCF3t-Bu 3-ClH 3-Br-2-pyridyl Bri-Pr 3-ClH 3-Br-2-pyridyl ClMe 6-ClH H CF3Et 6-Br4-MeH OCF3i-Pr 6-ClH H OCF3t-Bu 6-ClCl Me BrMe 6-ClH Et BrEt 6-ClH Me Cli-Pr 6-F 4-BrEt Clt-Bu 6-ClH Me Ipropargyl 6-ClH Me CF3cyclopropyl6-ClH Me OCF3i-Pr 6-Cl4-ClMe CF3
R3R4aR4bRvaRvbt-Bu 6-ClH Me SCF3Me 6-ClH Me SCHF2Et 6-ClH Me OCHF2i-Pr 6-I 4-CNMe CF3t-Bu 6-ClH Me C2F5propargyl 6-ClH Me C2F5cyclopropyl6-ClH Et CF3i-Pr 6-ClH n-PrCF3t-Bu 6-Cl4-Bri-PrCF3Me 6-ClH Cl CF3Et 6-F H F CF3i-Pr 6-ClH Me SMet-Bu 6-Cl4-ClMe OMeMe 6-ClH Me OEtEt 6-I H Me n-C3F7i-Pr 6-ClH Me i-C3F7t-Bu 6-Cl4-F Me Etpropargyl 6-ClH Me OCF2CHF2Et 6-ClH Me SCF2CHF2i-Pr 6-ClH Me SO2Met-Bu 6-Cl4-ClMe SO2CF3Me 6-ClH CF3CF3Et 6-ClH CF3Mei-Pr 6-ClH OMe CF3t-Bu 6-BrH H CF3cyclopropyl6-Cl4-BrH OCHF2Et 6-ClH H C2F5i-Pr 6-ClH H C2F5t-Bu 6-F 4-MeH OCF3Me 6-ClH H OCF2CHF2Et 6-ClH H SCF2CHF2i-Pr 6-CN4-ClH n-C3F7t-Bu 6-ClH H i-C3F7propargyl 6-ClH H BrEt 6-ClH H Cli-Pr 6-ClH H SCF3
R3R4aR4bRvaRvbt-Bu 6-Cl4-BrPh CF3cyclopropyl6-ClH Ph ClEt 6-F H Ph Bri-Pr 6-ClH 2-pyridyl CF3t-Bu 6-ClH 2-pyridyl ClMe 6-ClH 2-ClPh CF3Et 6-Br4-Cl2-ClPh OCF3i-Pr 6-ClH 2-ClPh Brt-Bu 6-ClH 2-ClPh ClMe 6-ClH 2-ClPh SCHF2propargyl 6-ClH 2-BrPh CF3i-Pr 6-BrH 2-MePh CF3t-Bu 6-Cl4-CN2-CNPh CF3Me 6-ClH 2-FPh CF3Et 6-ClH 2，6-F2Ph CF3i-Pr 6-Cl4-Br2，4-F2Ph CF3t-Bu 6-CNH 2，6-F2Ph CF3Me 6-Cl4-I 2-MeOPhCF3Et 6-ClH 3-Cl-2-pyridyl CF3i-Pr 6-BrH 3-Cl-2-pyridyl OCF3t-Bu 6-ClH 3-Cl-2-pyridyl Brpropargyl 6-ClH 3-Cl-2-pyridyl ClEt 6-Cl4-Br3-Cl-2-pyridyl SCHF2i-Pr 6-ClH 3-F-2-pyridyl CF3t-Bu 6-ClH 3-CF3-2-pyridyl CF3Me 6-ClH 3-Me-2-pyridyl CF3Et 6-ClH 3-Br-2-pyridyl CF3i-Pr 6-Cl4-Cl3-Br-2-pyridyl OCF3t-Bu 6-ClH 3-Br-2-pyridyl Bri-Pr 6-ClH 3-Br-2-pyridyl Cl
Table 12 R3R4aR4bR5aR5bMe 3-Me H H CF3Et 3-Me 5-Me H OCF3i-Pr 3-Me H H OCF3t-Bu 3-Me 5-Cl MeBrMe 3-Me H EtBrEt 3-Me H MeCli-Pr 3-Me 5-Br EtClt-Bu 3-Me H MeIpropargyl 3-Me H MeCF3cyclopropyl3-Me H MeOCF3i-Pr 3-Me 5-Cl MeCF3t-Bu 3-Me H MeSCF3Me 3-Me 5-CN MeSCHF2Et 3-Me H MeOCHF2i-Pr 3-Me H MeCF3t-Bu 3-Me H MeC2F5propargyl 3-Me H MeC2F5cyclopropyl3-Me H EtCF3i-Pr 3-Me H n-Pr CF3t-Bu 3-Me 5-Br i-Pr CF3Me 3-Me H ClCF3Et 3-Me H F CF3i-Pr 3-Me H MeSMet-Bu 3-Me 5-Cl MeOMeMe 3-Me H MeOEtEt 3-Me H Men-C3F7
R3R4aR4bR5aR5bi-Pr 3-MeH Me i-C3F7t-Bu 3-Me5-F Me Etpropargyl 3-MeH Me OCF2CHF2Et 3-MeH Me SCF2CHF2i-Pr 3-MeH Me SO2Met-Bu 3-Me5-ClMe SO2CF3Me 3-MeH CF3CF3Et 3-MeH CF3Mei-Pr 3-MeH OMe CF3t-Bu 3-MeH HCF3cyclopropyl3-Me5-BrHOCHF2Et 3-MeH HC2F5i-Pr 3-Me5-MeHC2F5t-Bu 3-MeH HOCF3Me 3-MeH HOCF2CHF2Et 3-MeH HSCF2CHF2i-Pr 3-Me5-ClHn-C3F7t-Bu 3-MeH Hi-C3F7propargyl 3-MeH HBrEt 3-MeH HCli-Pr 3-MeH HSCF3t-Bu 3-Me5-BrPh CF3cyclopropyl3-MeH Ph ClEt 3-MeH Ph Bri-Pr 3-MeH 2-pyridylCF3t-Bu 3-MeH 2-pyridylClMe 3-MeH 2-ClPh CF3Et 3-Me5-Cl2-ClPh OCF3i-Pr 3-MeH 2-ClPh Brt-Bu 3-MeH 2-ClPh ClMe 3-MeH 2-ClPh SCHF2propargyl 3-MeH 2-BrPh CF3i-Pr 3-Me5-CN2-MePh CF3t-Bu 3-MeH 2-CNPh CF3Me 3-MeH 2-FPhCF3Et 3-MeH 2，6-F2Ph CF3
R3R4aR4bR5aR5bi-Pr 3-Me5-Br2，4-F2Ph CF3t-Bu 3-MeH 2，6-F2Ph CF3Me 3-Me5-I 2-MeOPhCF3Et 3-MeH 3-Cl-2-pyridyl CF3i-Pr 3-Me5-Me3-Cl-2-pyridyl OCF3t-Bu 3-MeH 3-Cl-2-pyridyl Brpropargyl 3-MeH 3-Cl-2-pyridyl ClEt 3-Me5-Br3-Cl-2-pyridyl SCHF2i-Pr 3-MeH 3-F-2-pyridyl CF3t-Bu 3-MeH 3-CF3-2-pyridyl CF3Me 3-MeH 3-Me-2-pyridyl CF3Et 3-MeH 3-Br-2-pyridyl CF3i-Pr 3-Me5-Cl3-Br-2-pyridyl OCF3t-Bu 3-MeH 3-Br-2-pyridyl Bri-Pr 3-MeH 3-Br-2-pyridyl ClMe 6-MeH H CF3Et 6-Me4-MeH OCF3i-Pr 6-MeH H OCF3t-Bu 6-MeCl Me BrMe 6-MeH Et BrEt 6-MeH Me Cli-Pr 6-Me4-BrEt Clt-Bu 6-MeH Me Ipropargyl 6-MeH Me CF3cyclopropyl6-MeH Me OCF3i-Pr 6-Me4-ClMe CF3t-Bu 6-MeH Me SCF3Me 6-MeH Me SCHF2Et 6-MeH Me OCHF2i-Pr 6-Me4-CNMe CF3t-Bu 6-MeH Me C2F5propargyl 6-MeH Me C2F5cyclopropyl6-MeH Et CF3i-Pr 6-MeH n-Pr CF3t-Bu 6-Me4-Bri-Pr CF3Me 6-MeH Cl CF3
R3R4aR4bR5aR5bEt 6-MeH FCF3i-Pr 6-MeH Me SMet-Bu 6-Me4-ClMe OMeMe 6-MeH Me OEtEt 6-MeH Me n-C3F7i-Pr 6-MeH Me i-C3F7t-Bu 6-Me4-F Me Etpropargyl 6-MeH Me OCF2CHF2Et 6-MeH Me SCF2CHF2i-Pr 6-MeH Me SO2Met-Bu 6-Me4-ClMe SO2CF3Me 6-MeH CF3CF3Et 6-MeH CF3Mei-Pr 6-MeH OMe CF3t-Bu 6-MeH HCF3cyclopropyl6-Me4-BrHOCHF2Et 6-MeH HC2F5i-Pr 6-MeH HC2F5t-Bu 6-Me4-MeHOCF3Me 6-MeH HOCF2CHF2Et 6-MeH HSCF2CHF2i-Pr 6-Me4-ClHn-C3F7t-Bu 6-MeH Hi-C3F7propargyl 6-MeH HBrEt 6-MeH HCli-Pr 6-MeH HSCF3t-Bu 6-Me4-BrPh CF3cyclopropyl6-MeH Ph ClEt 6-MeH Ph Bri-Pr 6-MeH 2-pyridylCF3t-Bu 6-MeH 2-pyridylClMe 6-MeH 2-ClPh CF3Et 6-Me4-Cl2-ClPh OCF3i-Pr 6-MeH 2-ClPh Brt-Bu 6-Me4-CN2-ClPh ClMe 6-MeH 2-ClPh SCHF2
R3R4aR4bR5aR5bpropargyl 6-MeH 2-BrPh CF3i-Pr 6-MeH 2-MePh CF3t-Bu 6-MeH 2-CNPh CF3Me 6-MeH 2-FPh CF3Et 6-MeH 2，6-F2Ph CF3i-Pr 6-Me4-Br2，4-F2Ph CF3t-Bu 6-MeH 2，6-F2Ph CF3Me 6-Me4-I 2-MeOPhCF3Et 6-MeH 3-Cl-2-pyridyl CF3i-Pr 6-MeH 3-Cl-2-pyridyl OCF3t-Bu 6-MeH 3-Cl-2-pyridyl Brpropargyl 6-MeH 3-Cl-2-pyridyl ClEt 6-Me4-Br3-Cl-2-pyridyl SCHF2i-Pr 6-MeH 3-F-2-pyridyl CF3t-Bu 6-MeH 3-CF3-2-pyridyl CF3Me 6-MeH 3-Me-2-pyridyl CF3Et 6-MeH 3-Br-2-pyridyl CF3i-Pr 6-Me4-Cl3-Br-2-pyridyl OCF3t-Bu 6-MeH 3-Br-2-pyridyl Bri-Pr 6-MeH 3-Br-2-pyridyl ClMe 3-ClH H CF3Et 3-Br5-MeH OCF3i-Pr 3-ClH H OCF3t-Bu 3-Cl5-ClMe BrMe 3-ClH Et BrEt 3-ClH Me Cli-Pr 3-Cl5-BrEt Clt-Bu 3-ClH Me Ipropargyl 3-ClH Me CF3cyclopropyl3-ClH Me OCF3i-Pr 3-Cl5-ClMe CF3t-Bu 3-ClH Me SCF3Me 3-F H Me SCHF2Et 3-ClH Me OCHF2i-Pr 3-Cl5-CNMe CF3t-Bu 3-ClH Me C2F5
R3R4aR4bR5aR5bpropargyl 3-ClH Me C2F5cyclopropyl3-ClH Et CF3i-Pr 3-ClH n-Pr CF3t-Bu 3-Cl5-Bri-Pr CF3Me 3-ClH Cl CF3Et 3-BrH FCF3i-Pr 3-ClH Me SMet-Bu 3-Cl5-ClMe OMeMe 3-ClH Me OEtEt 3-ClH Me n-C3F7i-Pr 3-ClH Me i-C3F7t-Bu 3-Cl5-F Me Etpropargyl 3-ClH Me OCF2CHF2Et 3-ClH Me SCF2CHF2i-Pr 3-BrH Me SO2Met-Bu 3-Cl5-ClMe SO2CF3Me 3-ClH CF3CF3Et 3-CNH CF3Mei-Pr 3-ClH OMe CF3t-Bu 3-ClH HCF3cyclopropyl3-Cl5-BrHOCHF2Et 3-ClH HC2F5i-Pr 3-ClH HC2F5t-Bu 3-ClH HOCF3Me 3-F H HOCF2CHF2Et 3-ClH HSCF2CHF2i-Pr 3-Cl5-ClHn-C3F7t-Bu 3-ClH Hi-C3F7propargyl 3-ClH HBrEt 3-ClH HCli-Pr 3-ClH HSCF3t-Bu 3-Cl5-BrPh CF3cyclopropyl3-ClH Ph ClEt 3-ClH Ph Bri-Pr 3-BrH 2-pyridylCF3t-Bu 3-ClH 2-pyridylCl
R3R4aR4bR5aR5bMe 3-ClH 2-ClPh CF3Et 3-Cl5-Cl2-ClPh OCF3i-Pr 3-ClH 2-ClPh Brt-Bu 3-I H 2-ClPh ClMe 3-Cl5-Me2-ClPh SCHF2propargyl 3-ClH 2-BrPh CF3i-Pr 3-ClH 2-MePh CF3t-Bu 3-Cl5-CN2-CNPh CF3Me 3-ClH 2-FPh CF3Et 3-ClH 2，6-F2Ph CF3i-Pr 3-Cl5-Br2，4-F2Ph CF3t-Bu 3-F H 2，6-F2Ph CF3Me 3-Cl5-I 2-MeOPhCF3Et 3-ClH 3-Cl-2-pyridyl CF3i-Pr 3-CNH 3-Cl-2-pyridyl OCF3t-Bu 3-ClH 3-Cl-2-pyridyl Brpropargyl 3-ClH 3-Cl-2-pyridyl ClEt 3-Cl5-Br3-Cl-2-pyridyl SCHF2i-Pr 3-ClH 3-F-2-pyridyl CF3t-Bu 3-BrH 3-CF3-2-pyridyl CF3Me 3-ClH 3-Me-2-pyridyl CF3Et 3-ClH 3-Br-2-pyridyl CF3i-Pr 3-Cl5-Cl3-Br-2-pyridyl OCF3t-Bu 3-ClH 3-Br-2-pyridyl Bri-Pr 3-ClH 3-Br-2-pyridyl ClMe 6-ClH H CF3Et 6-Br4-MeH OCF3i-Pr 6-ClH H OCF3t-Bu 6-ClCl Me BrMe 6-ClH Et BrEt 6-ClH Me Cli-Pr 6-F 4-BrEt Clt-Bu 6-ClH Me Ipropargyl 6-ClH Me CF3cyclopropyl6-ClH Me OCF3i-Pr 6-Cl4-ClMe CF3
R3R4aR4bR5aR5bt-Bu 6-ClH Me SCF3Me 6-ClH Me SCHF2Et 6-ClH Me OCHF2i-Pr 6-I 4-CNMe CF3t-Bu 6-ClH Me C2F5propargyl 6-ClH Me C2F5cyclopropyl6-ClH Et CF3i-Pr 6-ClH n-PrCF3t-Bu 6-Cl4-Bri-PrCF3Me 6-ClH Cl CF3Et 6-F H F CF3i-Pr 6-ClH Me SMet-Bu 6-Cl4-ClMe OMeMe 6-ClH Me OEtEt 6-I H Me n-C3F7i-Pr 6-ClH Me i-C3F7t-Bu 6-Cl4-F Me Etpropargyl 6-ClH Me OCF2CHF2Et 6-ClH Me SCF2CHF2i-Pr 6-ClH Me SO2Met-Bu 6-Cl4-ClMe SO2CF3Me 6-ClH CF3CF3Et 6-ClH CF3Mei-Pr 6-ClH OMe CF3t-Bu 6-BrH H CF3cyclopropyl6-Cl4-BrH OCHF2Et 6-ClH H C2F5i-Pr 6-ClH H C2F5t-Bu 6-F 4-MeH OCF3Me 6-ClH H OCF2CHF2Et 6-ClH H SCF2CHF2i-Pr 6-CN4-ClH n-C3F7t-Bu 6-ClH H i-C3F7propargyl 6-ClH H BrEt 6-ClH H Cli-Pr 6-ClH H SCF3
R3R4aR4bR5aR5bt-Bu 6-Cl4-BrPh CF3cyclopropyl6-ClH Ph ClEt 6-F H Ph Bri-Pr 6-ClH 2-pyridyl CF3t-Bu 6-ClH 2-pyridyl ClMe 6-ClH 2-ClPh CF3Et 6-Br4-Cl2-ClPh OCF3i-Pr 6-ClH 2-ClPh Brt-Bu 6-ClH 2-ClPh ClMe 6-ClH 2-ClPh SCHF2propargyl 6-ClH 2-BrPh CF3i-Pr 6-BrH 2-MePh CF3t-Bu 6-Cl4-CN2-CNPh CF3Me 6-ClH 2-FPh CF3Et 6-ClH 2，6-F2Ph CF3i-Pr 6-Cl4-Br2，4-F2Ph CF3t-Bu 6-CNH 2，6-F2Ph CF3Me 6-Cl4-I 2-MeOPhCF3Et 6-ClH 3-Cl-2-pyridyl CF3i-Pr 6-BrH 3-Cl-2-pyridyl OCF3t-Bu 6-ClH 3-Cl-2-pyridyl Brpropargyl 6-ClH 3-Cl-2-pyridyl ClEt 6-Cl4-Br3-Cl-2-pyridyl SCHF2i-Pr 6-ClH 3-F-2-pyridyl CF3t-Bu 6-ClH 3-CF3-2-pyridyl CF3Me 6-ClH 3-Me-2-pyridyl CF3Et 6-ClH 3-Br-2-pyridyl CF3i-Pr 6-Cl4-Cl3-Br-2-pyridyl OCF3t-Bu 6-ClH 3-Br-2-pyridyl Bri-Pr 6-ClH 3-Br-2-pyridyl Cl
Table 13 R3R4aR4bRvaRvbMe 3-MeH H CF3Et 3-Me5-MeH OCF3i-Pr 3-MeH H OCF3t-Bu 3-Me5-ClMe BrMe 3-MeH Et BrEt 3-MeH Me Cli-Pr 3-Me5-BrEt Clt-Bu 3-MeH Me Ipropargyl 3-MeH Me CF3cyclopropyl3-MeH Me OCF3i-Pr 3-Me5-ClMe CF3t-Bu 3-MeH Me SCF3Me 3-Me5-CNMe SCHF2Et 3-MeH Me OCHF2i-Pr 3-MeH Me CF3t-Bu 3-MeH Me C2F5propargyl 3-MeH Me C2F5cyclopropyl3-MeH Et CF3i-Pr 3-MeH n-PrCF3t-Bu 3-Me5-Bri-PrCF3Me 3-MeH i-PrOCF3Et 3-MeH Me SMei-Pr 3-MeH Me OMet-Bu 3-Me5-ClMe OEtMe 3-MeH Me n-C3F7Et 3-MeH Me i-C3F7
R3R4aR4bRvaRvbi-Pr 3-MeH Me Ett-Bu 3-Me5-F Me OCF2CHF2propargyl 3-MeH Me SCF2CHF2Et 3-MeH Me SO2Mei-Pr 3-MeH Me SO2CF3t-Bu 3-Me5-ClCHF2CF3Me 3-MeH CHF2MeEt 3-MeH Ph CF3i-Pr 3-MeH Ph Clt-Bu 3-MeH Ph Brcyclopropyl3-Me5-Br2-pyridyl CF3Et 3-MeH 2-pyridyl Cli-Pr 3-Me5-Me2-ClPh CF3t-Bu 3-MeH 2-ClPh OCF3Me 3-MeH 2-ClPh BrEt 3-MeH 2-ClPh Cli-Pr 3-Me5-Cl2-ClPh SCHF2t-Bu 3-MeH 2-BrPh CF3propargyl 3-MeH 2-MePh CF3Et 3-MeH 2-CNPh CF3i-Pr 3-MeH 2-FPh CF3t-Bu 3-Me5-Br2，6-F2Ph CF3cyclopropyl3-MeH 2，4-F2Ph CF3Et 3-MeH 2，5-F2Ph CF3i-Pr 3-MeH 2-MeOPhCF3t-Bu 3-MeH 3-Cl-2-pyridyl CF3Me 3-MeH 3-Cl-2-pyridyl OCF3Et 3-Me5-Cl3-Cl-2-pyridyl Bri-Pr 3-MeH 3-Cl-2-pyridyl Clt-Bu 3-MeH 3-Cl-2-pyridyl SCHF2Me 3-MeH 3-F-2-pyridyl CF3propargyl 3-MeH 3-CF3-2-pyridyl CF3i-Pr 3-Me5-CN3-Me-2-pyridyl CF3t-Bu 3-MeH 3-Br-2-pyridyl CF3Me 3-MeH 3-Br-2-pyridyl OCF3Et 3-MeH 3-Br-2-pyridyl Br
R3R4aR4bRvaRvbi-Pr 3-Me5-Br3-Br-2-pyridylClMe 6-MeH H CF3Et 6-Me4-MeH OCF3i-Pr 6-MeH H OCF3t-Bu 6-MeCl MeBrMe 6-MeH EtBrEt 6-MeH MeCli-Pr 6-Me4-BrEtClt-Bu 6-MeH MeIpropargyl 6-MeH MeCF3cyclopropyl6-MeH MeOCF3i-Pr 6-Me4-ClMeCF3t-Bu 6-MeH MeSCF3Me 6-MeH MeSCHF2Et 6-MeH MeOCHF2i-Pr 6-Me4-CNMeCF3t-Bu 6-MeH MeC2F5propargyl 6-MeH MeC2F5cyclopropyl6-MeH EtCF3i-Pr 6-MeH n-Pr CF3t-Bu 6-Me4-Bri-Pr CF3Me 6-MeH MeSMeEt 6-MeH MeOMei-Pr 6-MeH MeOEtt-Bu 6-Me4-ClMen-C3F7Me 6-MeH Mei-C3F7Et 6-MeH MeEti-Pr 6-MeH MeOCF2CHF2t-Bu 6-Me4-F MeSCF2CHF2propargyl 6-MeH MeSO2MeEt 6-MeH MeSO2CF3i-Pr 6-MeH CF3CF3t-Bu 6-Me4-ClCF3MeMe 6-MeH PhCf3Et 6-MeH PhCli-Pr 6-MeH PhBr
R3R4aR4bRvaRvbt-Bu 6-MeH 2-pyridyl CF3cyclopropyl6-Me4-Br2-pyridyl ClEt 6-MeH 2-ClPh CF3i-Pr 6-MeH 2-ClPh OCF3t-Bu 6-Me4-Me2-ClPh BrMe 6-MeH 2-ClPh ClEt 6-MeH 2-ClPh SCHF2i-Pr 6-Me4-Cl2-BrPh CF3t-Bu 6-MeH 2-Meph CF3propargyl 6-MeH 2-CNPh CF3Et 6-MeH 2-FPh CF3i-Pr 6-MeH 2，6-F2Ph CF3t-Bu 6-Me4-Br2，4-F2Ph CF3cyclopropyl6-MeH 2，5-F2Ph CF3Et 6-MeH 2-MeOPhCF3i-Pr 6-MeH 3-Cl-2-pyridyl CF3t-Bu 6-MeH 3-Cl-2-pyridyl OCF3Me 6-MeH 3-Cl-2-pyridyl BrEt 6-Me4-Cl3-Cl-2-pyridyl Cli-Pr 6-MeH 3-Cl-2-pyridyl SCHF2t-Bu 6-Me4-CN3-F-2-pyridyl CF3Me 6-MeH 3-CF3-2-pyridyl CF3propargyl 6-MeH 3-Me-2-pyridyl CF3i-Pr 6-MeH 3-Br-2-pyridyl CF3t-Bu 6-MeH 3-Br-2-pyridyl OCF3Me 6-MeH 3-Br-2-pyridyl BrEt 6-MeH 3-Br-2-pyridyl ClMe 3-ClH Me BrEt 3-Br5-MeEt Bri-Pr 3-ClH Me Clt-Bu 3-Cl5-ClEt ClMe 3-ClH Me IEt 3-ClH Me CF3i-Pr 3-Cl5-BrMe OCF3t-Bu 3-ClH Me CF3
R3R4aR4bRvaRvbpropargyl 3-ClH Me SCF3cyclopropyl3-ClH Me SCHF2i-Pr 3-Cl5-ClMe OCHF2t-Bu 3-ClH Me CF3Me 3-F H Me C2F5Et 3-ClH Me C2F5i-Pr 3-Cl5-CNEt CF3t-Bu 3-ClH n-Pr CF3propargyl 3-ClH i-Pr CF3cyclopropyl3-ClH Me SMei-Pr 3-ClH Me OMet-Bu 3-Cl5-BrMe OEtMe 3-ClH Me n-C3F7Et 3-BrH Me i-C3F7i-Pr 3-ClH Me Ett-Bu 3-Cl5-ClMe OCF2CHF2Me 3-ClH Me SCF2CHF2Et 3-ClH Me SO2Mei-Pr 3-ClH Me SO2CF3t-Bu 3-Cl5-F CF3CF3propargyl 3-ClH CF3MeEt 3-ClH Ph CF3i-Pr 3-BrH Ph Clt-Bu 3-Cl5-ClPh BrMe 3-ClH 2-pyridylCF3Et 3-CNH 2-pyridylCli-Pr 3-ClH 2-ClPh CF3t-Bu 3-ClH 2-ClPh OCF3cyclopropyl3-Cl5-Br2-ClPh BrEt 3-ClH 2-ClPh Cli-Pr 3-ClH 2-ClPh OCF3t-Bu 3-ClH 2-BrPh CF3Me 3-F H 2-MePh CF3Et 3-ClH 2-CNPh CF3i-Pr 3-Cl5-Cl2-FPhCF3t-Bu 3-ClH 2，6-F2Ph CF3
R3R4aR4bRvaRvbpropargyl 3-ClH 2，4-F2Ph CF3Et 3-ClH 2，5-F2Ph CF3i-Pr 3-ClH 2-MeOPhCF3t-Bu 3-Cl5-Br3-Cl-2-pyridyl CF3cyclopropyl3-ClH 3-Cl-2-pyridyl OCF3Et 3-ClH 3-Cl-2-pyridyl Bri-Pr 3-BrH 3-Cl-2-pyridyl Clt-Bu 3-ClH 3-Cl-2-pyridyl SCHF2Me 3-ClH 3-F-2-pyridyl CF3Et 3-Cl5-Cl3-CF3-2-pyridyl CF3i-Pr 3-ClH 3-Me-2-pyridyl CF3t-Bu 3-I H 3-Br-2-pyridyl CF3Me 3-Cl5-Me3-Br-2-pyridyl OCF3propargyl 3-ClH 3-Br-2-pyridyl Bri-Pr 3-ClH 3-Br-2-pyridyl ClMe 6-ClH Et BrEt 6-Br4-MeMe Cli-Pr 6-ClH Et Clt-Bu 6-ClCl Me IMe 6-ClH Me CF3Et 6-ClH Me OCF3i-Pr 6-F 4-BrMe CF3t-Bu 6-ClH Me SCF3propargyl 6-ClH Me SCHF2cyclopropyl6-ClH Me OCHF2i-Pr 6-Cl4-ClMe CF3t-Bu 6-ClH Me C2F5Me 6-ClH Me C2F5Et 6-ClH Et CF3i-Pr 6-l 4-CNn-Pr CF3t-Bu 6-ClH i-Pr CF3propargyl 6-ClH Me SMecyclopropyl6-ClH Me OMei-Pr 6-ClH Me OEtt-Bu 6-Cl4-BrMe n-C3F7Me 6-ClH Me i-C3F7
R3R4aR4bRvaRvbEt 6-F H Me Eti-Pr 6-ClH Me OCF2CHF2t-Bu 6-Cl4-ClMe SCF2CHF2Me 6-ClH Me SO2MeEt 6-I H Me SO2CF3i-Pr 6-ClH CF3CF3t-Bu 6-Cl4-F CF3Mepropargyl 6-ClH Ph CF3Et 6-ClH Ph Cli-Pr 6-ClH Ph Brt-Bu 6-Cl4-Cl2-pyridyl CF3Me 6-ClH 2-pyridyl ClEt 6-ClH 2-ClPh CF3i-Pr 6-ClH 2-ClPh OCF3t-Bu 6-BrH 2-ClPh Brcyclopropyl6-Cl4-Br2-ClPh ClEt 6-ClH 2-ClPh SCHF2i-Pr 6-ClH 2-BrPh CF3t-Bu 6-F 4-Me2-MePh CF3Me 6-ClH 2-CNPh CF3Et 6-ClH 2-FPh CF3i-Pr 6-CN4-Cl2，6-F2Ph CF3t-Bu 6-ClH 2，4-F2Ph CF3propargyl 6-ClH 2，5-F2Ph CF3Et 6-ClH 2-MeOPhCF3i-Pr 6-ClH 3-Cl-2-pyridyl CF3t-Bu 6-Cl4-Br3-Cl-2-pyridyl OCF3cyclopropyl6-ClH 3-Cl-2-pyridyl BrEt 6-F H 3-Cl-2-pyridyl Cli-Pr 6-ClH 3-Cl-2-pyridyl SCHF2t-Bu 6-ClH 3-F-2-pyridyl CF3Me 6-ClH 3-CF3-2-pyridyl CF3Et 6-Br4-Cl3-Me-2-pyridyl CF3i-Pr 6-ClH 3-Br-2-pyridyl CF3t-Bu 6-ClH 3-Br-2-pyridyl OCF3Me 6-ClH 3-Br-2-pyridyl Br
R3R4aR4bRvaRvbpropargyl 6-ClH 3-Br-2-pyridylClTable 14 R3R4aR4bRvaRvbMe 3-MeH H CF3Et 3-Me5-MeH OCF3i-Pr 3-MeH H OCF3t-Bu 3-Me5-ClMeBrMe 3-MeH EtBrEt 3-MeH MeCli-Pr 3-Me5-BrEtClt-Bu 3-MeH MeIpropargyl 3-MeH MeCF3cyclopropyl3-MeH MeOCF3i-Pr 3-Me5-ClMeCF3t-Bu 3-MeH MeSCF3Me 3-Me5-CNMeSCHF2Et 3-MeH MeOCHF2i-Pr 3-MeH MeCF3t-Bu 3-MeH MeC2F5propargyl 3-MeH MeC2F5cyclopropyl3-MeH EtCF3i-Pr 3-MeH n-Pr CF3t-Bu 3-Me5-Bri-Pr CF3Me 3-MeH i-Pr OCF3Et 3-MeH MeSMe
R3R4aR4bRvaRvbi-Pr 3-MeH Me OMet-Bu 3-Me5-ClMe OEtMe 3-MeH Me n-C3F7Et 3-MeH Me i-C3F7i-Pr 3-MeH Me Ett-Bu 3-Me5-F Me OCF2CHF2propargyl 3-MeH Me SCF2CHF2Et 3-MeH Me SO2Mei-Pr 3-MeH Me SO2CF3t-Bu 3-Me5-ClCHF2CF3Me 3-MeH CHF2MeEt 3-MeH Ph CF3i-Pr 3-MeH Ph Clt-Bu 3-MeH Ph Brcyclopropyl3-Me5-Br2-pyridyl CF3Et 3-MeH 2-pyridyl Cli-Pr 3-Me5-Me2-ClPh CF3t-Bu 3-MeH 2-ClPh OCF3Me 3-MeH 2-ClPh BrEt 3-MeH 2-ClPh Cli-Pr 3-Me5-Cl2-ClPh SCHF2t-Bu 3-MeH 2-BrPh CF3propargyl 3-MeH 2-MePh CF3Et 3-MeH 2-CNPh CF3i-Pr 3-MeH 2-FPh CF3t-Bu 3-Me5-Br2，6-F2Ph CF3cyclopropyl3-MeH 2，4-F2Ph CF3Et 3-MeH 2，5-F2Ph CF3i-Pr 3-MeH 2-MeOPhCF3t-Bu 3-MeH 3-Cl-2-pyridyl CF3Me 3-MeH 3-Cl-2-pyridyl OCF3Et 3-Me5-Cl3-Cl-2-pyridyl Bri-Pr 3-MeH 3-Cl-2-pyridyl Clt-Bu 3-MeH 3-Cl-2-pyridyl SCHF2Me 3-MeH 3-F-2-pyridyl CF3propargyl 3-MeH 3-CF3-2-pyridyl CF3
R3R4aR4bRvaRvbi-Pr 3-Me5-CN3-Me-2-pyridylCF3t-Bu 3-MeH 3-Br-2-pyridylCF3Me 3-MeH 3-Br-2-pyridylOCF3Et 3-MeH 3-Br-2-pyridylBri-Pr 3-Me5-Br3-Br-2-pyridylClMe 6-MeH H CF3Et 6-Me4-MeH OCF3i-Pr 6-MeH H OCF3t-Bu 6-MeCl MeBrMe 6-MeH EtBrEt 6-MeH MeCli-Pr 6-Me4-BrEtClt-Bu 6-MeH MeIpropargyl 6-MeH MeCF3cyclopropyl6-MeH MeOCF3i-Pr 6-Me4-ClMeCF3t-Bu 6-MeH MeSCF3Me 6-MeH MeSCHF2Et 6-MeH MeOCHF2i-Pr 6-Me4-CNMeCF3t-Bu 6-MeH MeC2F5propargyl 6-MeH MeC2F5cyclopropyl6-MeH EtCF3i-Pr 6-MeH n-Pr CF3t-Bu 6-Me4-Bri-Pr CF3Me 6-MeH MeSMeEt 6-MeH MeOMei-Pr 6-MeH MeOEtt-Bu 6-Me4-ClMen-C3F7Me 6-MeH Mei-C3F7Et 6-MeH MeEti-Pr 6-MeH MeOCF2CHF2t-Bu 6-Me4-F MeSCF2CHF2propargyl 6-MeH MeSO2MeEt 6-MeH MeSO2CF3i-Pr 6-MeH CF3CF3
R3R4aR4bRvaRvbt-Bu 6-Me4-ClCF3MeMe 6-MeH Ph CF3Et 6-MeH Ph Cli-Pr 6-MeH Ph Brt-Bu 6-MeH 2-pyridyl CF3cyclopropyl6-Me4-Br2-pyridyl ClEt 6-MeH 2-ClPh CF3i-Pr 6-MeH 2-ClPh OCF3t-Bu 6-Me4-Me2-ClPh BrMe 6-MeH 2-ClPh ClEt 6-MeH 2-ClPh SCHF2i-Pr 6-Me4-Cl2-BrPh CF3t-Bu 6-MeH 2-MePh CF3propargyl 6-MeH 2-CNPh CF3Et 6-MeH 2-FPh CF3i-Pr 6-MeH 2，6-F2Ph CF3t-Bu 6-Me4-Br2，4-F2Ph CF3cyclopropyl6-MeH 2，5-F2Ph CF3Et 6-MeH 2-MeOPhCF3i-Pr 6-MeH 3-Cl-2-pyridyl CF3t-Bu 6-MeH 3-Cl-2-pyridyl OCF3Me 6-MeH 3-Cl-2-pyridyl BrEt 6-Me4-Cl3-Cl-2-pyridyl Cli-Pr 6-MeH 3-Cl-2-pyridyl SCHF2t-Bu 6-Me4-CN3-F-2-pyridyl CF3Me 6-MeH 3-CF3-2-pyridyl CF3propargyl 6-MeH 3-Me-2-pyridyl CF3i-Pr 6-MeH 3-Br-2-pyridyl CF3t-Bu 6-MeH 3-Br-2-pyridyl OCF3Me 6-MeH 3-Br-2-pyridyl BrEt 6-MeH 3-Br-2-pyridyl ClMe 3-ClH Me BrEt 3-Br5-MeEt Bri-Pr 3-ClH Me Clt-Bu 3-Cl5-ClEt ClMe 3-ClH Me I
R3R4aR4bRvaRvbEt 3-ClH Me CF3i-Pr 3-Cl5-BrMe OCF3t-Bu 3-ClH Me CF3propargyl 3-ClH Me SCF3cyclopropyl3-ClH Me SCHF2i-Pr 3-Cl5-ClMe OCHF2t-Bu 3-ClH Me CF3Me 3-F H Me C2F5Et 3-ClH Me C2F5i-Pr 3-Cl5-CNEt CF3t-Bu 3-ClH n-Pr CF3propargyl 3-ClH i-Pr CF3cyclopropyl3-ClH Me SMei-Pr 3-ClH Me OMet-Bu 3-Cl5-BrMe OEtMe 3-ClH Me n-C3F7Et 3-BrH Me i-C3F7i-Pr 3-ClH Me Ett-Bu 3-Cl5-ClMe OCF2CHF2Me 3-ClH Me SCF2CHF2Et 3-ClH Me SO2Mei-Pr 3-ClH Me SO2CF3t-Bu 3-Cl5-F CF3CF3propargyl 3-ClH CF3MeEt 3-ClH Ph CF3i-Pr 3-BrH Ph Clt-Bu 3-Cl5-ClPh BrMe 3-ClH 2-pyridylCF3Et 3-CNH 2-pyridylCli-Pr 3-ClH 2-ClPh CF3t-Bu 3-ClH 2-ClPh OCF3cyclopropyl3-Cl5-Br2-ClPh BrEt 3-ClH 2-ClPh Cli-Pr 3-ClH 2-ClPh OCF3t-Bu 3-ClH 2-BrPh CF3Me 3-F H 2-MePh CF3
R3R4aR4bRvaRvbEt 3-ClH 2-CNPh CF3i-Pr 3-Cl5-Cl2-FPh CF3t-Bu 3-ClH 2，6-F2Ph CF3propargyl 3-ClH 2，4-F2Ph CF3Et 3-ClH 2，5-F2Ph CF3i-Pr 3-ClH 2-MeOPhCF3t-Bu 3-Cl5-Br3-Cl-2-pyridyl CF3cyclopropyl3-ClH 3-Cl-2-pyridyl OCF3Et 3-ClH 3-Cl-2-pyridyl Bri-Pr 3-BrH 3-Cl-2-pyridyl Clt-Bu 3-ClH 3-Cl-2-pyridyl SCHF2Me 3-ClH 3-F-2-pyridyl CF3Et 3-Cl5-Cl3-CF3-2-pyridyl CF3i-Pr 3-ClH 3-Me-2-pyridyl CF3t-Bu 3-I H 3-Br-2-pyridyl CF3Me 3-Cl5-Me3-Br-2-pyridyl OCF3propargyl 3-ClH 3-Br-2-pyridyl Bri-Pr 3-ClH 3-Br-2-pyridyl ClMe 6-ClH Et BrEt 6-Br4-MeMe Cli-Pr 6-ClH Et Clt-Bu 6-ClCl Me IMe 6-ClH Me CF3Et 6-ClH Me OCF3i-Pr 6-F 4-BrMe CF3t-Bu 6-ClH Me SCF3propargyl 6-ClH Me SCHF2cyclopropyl6-ClH Me OCHF2i-Pr 6-Cl4-ClMe CF3t-Bu 6-ClH Me C2F5Me 6-ClH Me C2F5Et 6-ClH Et CF3i-Pr 6-I 4-CNn-Pr CF3t-Bu 6-ClH i-Pr CF3propargyl 6-ClH Me SMecyclopropyl6-ClH Me OMe
R3R4aR4bRvaRvbi-Pr 6-ClH Me OEtt-Bu 6-Cl4-BrMe n-C3F7Me 6-ClH Me i-C3F7Et 6-F H Me Eti-Pr 6-ClH Me OCF2CHF2t-Bu 6-Cl4-ClMe SCF2CHF2Me 6-ClH Me SO2MeEt 6-I H Me SO2CF3i-Pr 6-ClH CF3CF3t-Bu 6-Cl4-F CF3Mepropargyl 6-ClH Ph CF3Et 6-ClH Ph Cli-Pr 6-ClH Ph Brt-Bu 6-Cl4-Cl2-pyridyl CF3Me 6-ClH 2-pyridyl ClEt 6-ClH 2-ClPh CF3i-Pr 6-ClH 2-ClPh OCF3t-Bu 6-BrH 2-ClPh Brcyclopropyl6-Cl4-Br2-ClPh ClEt 6-ClH 2-ClPh SCHF2i-Pr 6-ClH 2-BrPh CF3t-Bu 6-F 4-Me2-MePh CF3Me 6-ClH 2-CNPh CF3Et 6-ClH 2-FPh CF3i-Pr 6-CN4-Cl2，6-F2Ph CF3t-Bu 6-ClH 2，4-F2Ph CF3propargyl 6-ClH 2，5-F2Ph CF3Et 6-ClH 2-MeOPhCF3i-Pr 6-ClH 3-Cl-2-pyridyl CF3t-Bu 6-Cl4-Br3-Cl-2-pyridyl OCF3cyclopropyl6-ClH 3-Cl-2-pyridyl BrEt 6-F H 3-Cl-2-pyridyl Cli-Pr 6-ClH 3-Cl-2-pyridyl SCHF2t-Bu 6-ClH 3-F-2-pyridyl CF3Me 6-ClH 3-CF3-2-pyridyl CF3Et 6-Br4-Cl3-Me-2-pyridyl CF3
R3R4aR4bRvaRvbi-Pr 6-ClH 3-Br-2-pyridylCF3t-Bu 6-ClH 3-Br-2-pyridylOCF3Me 6-ClH 3-Br-2-pyridylBrpropargyl 6-ClH 3-Br-2-pyridylClTable 15 R3R4aR4bRvaRvbMe 3-MeH H CF3Et 3-Me5-MeH OCF3i-Pr 3-MeH H OCF3t-Bu 3-Me5-ClMeBrMe 3-MeH EtBrEt 3-MeH MeCli-Pr 3-Me5-BrEtClt-Bu 3-MeH MeIpropargyl 3-MeH MeCF3cyclopropyl3-MeH MeOCF3i-Pr 3-Me5-ClMeCF3t-Bu 3-MeH MeSCF3Me 3-Me5-CNMeSCHF2Et 3-MeH MeOCHF2i-Pr 3-MeH MeCF3t-Bu 3-MeH MeC2F5propargyl 3-MeH MeC2F5cyclopropyl3-MeH EtCF3i-Pr 3-MeH n-Pr CF3
R3R4aR4bRvaRvbt-Bu 3-Me5-Bri-Pr CF3Me 3-MeH i-Pr OCF3Et 3-MeH MeSMei-Pr 3-MeH MeOMet-Bu 3-Me5-ClMeOEtMe 3-MeH Men-C3F7Et 3-MeH Mei-C3F7i-Pr 3-MeH MeEtt-Bu 3-Me5-F MeOCF2CHF2propargyl 3-MeH MeSCF2CHF2Et 3-MeH MeSO2Mei-Pr 3-MeH MeSO2CF3t-Bu 3-Me5-ClCHF2CF3Me 3-MeH CHF2MeEt 3-MeH PhCF3i-Pr 3-MeH PhClt-Bu 3-MeH PhBrcyclopropyl3-Me5-Br2-pyridyl CF3Et 3-MeH 2-pyridyl Cli-Pr 3-Me5-Me2-ClPhCF3t-Bu 3-MeH 2-ClPhOCF3Me 3-MeH 2-ClPhBrEt 3-MeH 2-ClPhCli-Pr 3-Me5-Cl2-ClPhSCHF2t-Bu 3-MeH 2-BrPhCF3propargyl 3-MeH 2-MePhCF3Et 3-MeH 2-CNPhCF3i-Pr 3-MeH 2-FPh CF3t-Bu 3-Me5-Br2，6-F2PhCF3cyclopropyl3-MeH 2，4-F2PhCF3Et 3-MeH 2，5-F2PhCF3i-Pr 3-MeH 2-MeOPh CF3t-Bu 3-MeH 3-Cl-2-pyridylCF3Me 3-MeH 3-Cl-2-pyridylOCF3Et 3-Me5-Cl3-Cl-2-pyridylBri-Pr 3-MeH 3-Cl-2-pyridylCl
R3R4aR4bRvaRvbt-Bu 3-MeH 3-Cl-2-pyridyl SCHF2Me 3-MeH 3-F-2-pyridyl CF3propargyl 3-MeH 3-CF3-2-pyridyl CF3i-Pr 3-Me5-CN3-Me-2-pyridyl CF3t-Bu 3-MeH 3-Br-2-pyridyl CF3Me 3-MeH 3-Br-2-pyridyl OCF3Et 3-MeH 3-Br-2-pyridyl Bri-Pr 3-Me5-Br3-Br-2-pyridyl ClMe 6-MeH H CF3Et 6-Me4-MeH OCF3i-Pr 6-MeH H OCF3t-Bu 6-MeCl Me BrMe 6-MeH Et BrEt 6-MeH Me Cli-Pr 6-Me4-BrEt Clt-Bu 6-MeH Me Ipropargyl 6-MeH Me CF3cyclopropyl6-MeH Me OCF3i-Pr 6-Me4-ClMe CF3t-Bu 6-MeH Me SCF3Me 6-MeH Me SCHF2Et 6-MeH Me OCHF2i-Pr 6-Me4-CNMe CF3t-Bu 6-MeH Me C2F5propargyl 6-MeH Me C2F5cyclopropyl6-MeH Et CF3i-Pr 6-MeH n-Pr CF3t-Bu 6-Me4-Bri-Pr CF3Me 6-MeH Me SMeEt 6-MeH Me OMei-Pr 6-MeH Me OEtt-Bu 6-Me4-ClMe n-C3F7Me 6-MeH Me i-C3F7Et 6-MeH Me Eti-Pr 6-MeH Me OCF2CHF2t-Bu 6-Me4-F Me SCF2CHF2
R3R4aR4bRvaRvbpropargyl 6-MeH Me SO2MeEt 6-MeH Me SO2CF3i-Pr 6-MeH CF3CF3t-Bu 6-Me4-ClCF3MeMe 6-MeH Ph CF3Et 6-MeH Ph Cli-Pr 6-MeH Ph Brt-Bu 6-MeH 2-pyridyl CF3cyclopropyl6-Me4-Br2-pyridyl ClEt 6-MeH 2-ClPh CF3i-Pr 6-MeH 2-ClPh OCF3t-Bu 6-Me4-Me2-ClPh BrMe 6-MeH 2-ClPh ClEt 6-MeH 2-ClPh SCHF2i-Pr 6-Me4-Cl2-BrPh CF3t-Bu 6-MeH 2-MePh CF3propargyl 6-MeH 2-CNPh CF3Et 6-MeH 2-FPh CF3i-Pr 6-MeH 2，6-F2Ph CF3t-Bu 6-Me4-Br2，4-F2Ph CF3cyclopropyl6-MeH 2，5-F2Ph CF3Et 6-MeH 2-MeOPhCF3i-Pr 6-MeH 3-Cl-2-pyridyl CF3t-Bu 6-MeH 3-Cl-2-pyridyl OCF3Me 6-MeH 3-Cl-2-pyridyl BrEt 6-Me4-Cl3-Cl-2-pyridyl Cli-Pr 6-MeH 3-Cl-2-pyridyl SCHF2t-Bu 6-Me4-CN3-F-2-pyridyl CF3Me 6-MeH 3-CF3-2-pyridyl CF3propargyl 6-MeH 3-Me-2-pyridyl CF3i-Pr 6-MeH 3-Br-2-pyridyl CF3t-Bu 6-MeH 3-Br-2-pyridyl OCF3Me 6-MeH 3-Br-2-pyridyl BrEt 6-MeH 3-Br-2-pyridyl ClMe 3-ClH Me BrEt 3-Br5-MeEt Br
R3R4aR4bRvaRvbi-Pr 3-ClH Me Clt-Bu 3-Cl5-ClEt ClMe 3-ClH Me lEt 3-ClH Me CF3i-Pr 3-Cl5-BrMe OCF3t-Bu 3-ClH Me CF3propargyl 3-ClH Me SCF3cyclopropyl3-ClH Me SCHF2i-Pr 3-Cl5-ClMe OCHF2t-Bu 3-ClH Me CF3Me 3-F H Me C2F5Et 3-ClH Me C2F5i-Pr 3-Cl5-CNEt CF3t-Bu 3-ClH n-Pr CF3propargyl 3-ClH i-Pr CF3cyclopropyl3-ClH Me SMei-Pr 3-ClH Me OMet-Bu 3-Cl5-BrMe OEtMe 3-ClH Me n-C3F7Et 3-BrH Me i-C3F7i-Pr 3-ClH Me Ett-Bu 3-Cl5-ClMe OCF2CHF2Me 3-ClH Me SCF2CHF2Et 3-ClH Me SO2Mei-Pr 3-ClH Me SO2CF3t-Bu 3-Cl5-F CF3CF3propargyl 3-ClH CF3MeEt 3-ClH Ph CF3i-Pr 3-BrH Ph Clt-Bu 3-Cl5-ClPh BrMe 3-ClH 2-pyridylCF3Et 3-CNH 2-pyridylCli-Pr 3-ClH 2-ClPh CF3t-Bu 3-ClH 2-ClPh OCF3cyclopropyl3-Cl5-Br2-ClPh BrEt 3-ClH 2-ClPh Cl
R3R4aR4bRvaRvbi-Pr 3-ClH 2-ClPh OCF3t-Bu 3-ClH 2-BrPh CF3Me 3-F H 2-MePh CF3Et 3-ClH 2-CNPh CF3i-Pr 3-Cl5-Cl2-FPh CF3t-Bu 3-ClH 2，6-F2Ph CF3propargyl 3-ClH 2，4-F2Ph CF3Et 3-ClH 2，5-F2Ph CF3i-Pr 3-ClH 2-MeOPhCF3t-Bu 3-Cl5-Br3-Cl-2-pyridyl CF3cyclopropyl3-ClH 3-Cl-2-pyridyl OCF3Et 3-ClH 3-Cl-2-pyridyl Bri-Pr 3-BrH 3-Cl-2-pyridyl Clt-Bu 3-ClH 3-Cl-2-pyridyl SCHF2Me 3-ClH 3-F-2-pyridyl CF3Et 3-Cl5-Cl3-CF3-2-pyridyl CF3i-Pr 3-ClH 3-Me-2-pyridylCF3t-Bu 3-l H 3-Br-2-pyridylCF3Me 3-Cl5-Me3-Br-2-pyridylOCF3propargyl 3-ClH 3-Br-2-pyridylBri-Pr 3-ClH 3-Br-2-pyridylClMe 6-ClH EtBrEt 6-Br4-MeMeCli-Pr 6-ClH EtClt-Bu 6-ClCl MeIMe 6-ClH MeCF3Et 6-ClH MeOCF3i-Pr 6-F 4-BrMeCF3t-Bu 6-ClH MeSCF3propargyl 6-ClH MeSCHF2cyclopropyl6-ClH MeOCHF2i-Pr 6-Cl4-ClMeCF3t-Bu 6-ClH MeC2F5Me 6-ClH MeC2F5Et 6-ClH EtCF3i-Pr 6-I 4-CNn-Pr CF3
R3R4aR4bRvaRvbt-Bu 6-ClH i-Pr CF3propargyl 6-ClH MeSMecyclopropyl6-ClH MeOMei-Pr 6-ClH MeOEtt-Bu 6-Cl4-BrMen-C3F7Me 6-ClH Mei-C3F7Et 6-F H MeEti-Pr 6-ClH MeOCF2CHF2t-Bu 6-Cl4-ClMeSCF2CHF2Me 6-ClH MeSO2MeEt 6-I H MeSO2CF3i-Pr 6-ClH CF3CF3t-Bu 6-Cl4-F CF3Mepropargyl 6-ClH PhCF3Et 6-ClH PhCli-Pr 6-ClH PhBrt-Bu 6-Cl4-Cl2-pyridyl CF3Me 6-ClH 2-pyridyl ClEt 6-ClH 2-ClPHCF3i-Pr 6-ClH 2-ClPhOCF3t-Bu 6-BrH 2-ClPhBrcyclopropyl6-Cl4-Br2-ClPhClEt 6-ClH 2-ClPhSCHF2i-Pr 6-ClH 2-BrPhCF3t-Bu 6-F 4-Me2-MePhCF3Me 6-ClH 2-CNPhCF3Et 6-ClH 2-FPh CF3i-Pr 6-CN4-Cl2，6-F2PhCF3t-Bu 6-ClH 2，4-F2PhCF3propargyl 6-ClH 2，5-F2PhCF3Et 6-ClH 2-MeOPh CF3i-Pr 6-ClH 3-Cl-2-pyridylCF3t-Bu 6-Cl4-Br3-Cl-2-pyridylOCF3cyclopropyl6-ClH 3-Cl-2-pyridylBrEt 6-F H 3-Cl-2-pyridylCli-Pr 6-ClH 3-Cl-2-pyridylSCHF2
R3R4aR4bRvaRvbt-Bu 6-ClH 3-F-2-pyridyl CF3Me 6-ClH 3-CF3-2-pyridyl CF3Et 6-Br4-Cl3-Me-2-pyridyl CF3i-Pr 6-ClH 3-Br-2-pyridyl CF3t-Bu 6-ClH 3-Br-2-pyridyl OCF3Me 6-ClH 3-Br-2-pyridyl Brpropargyl 61-Cl H 3-Br-2-pyridyl ClTable 16 R3R4aR4bRvaRvbMe 3-MeH H CF3Et 3-Me5-MeH OCF3i-Pr 3-MeH H OCF3t-Bu 3-Me5-ClMe BrMe 3-MeH Et BrEt 3-MeH Me Cli-Pr 3-Me5-BrEt Clt-Bu 3-MeH Me Ipropargyl 3-MeH Me CF3cyclopropyl3-MeH Me OCF3i-Pr 3-Me5-ClMe CF3t-Bu 3-MeH Me SCF3Me 3-Me5-CNMe SCHF2Et 3-MeH Me OCHF2i-Pr 3-MeH Me CF3t-Bu 3-MeH Me C2F5
R3R4aR4bRvaRvbropargyl 3-MeH MeC2F5cyclopropyl3-MeH EtCF3i-Pr 3-MeH n-Pr CF3t-Bu 3-Me5-Bri-Pr CF3Me 3-MeH i-Pr OCF3Et 3-MeH MeSMei-Pr 3-MeH MeOMet-Bu 3-Me5-ClMeOEtMe 3-MeH Men-C3F7Et 3-MeH Mei-C3F7i-Pr 3-MeH MeEtt-Bu 3-Me5-F MeOCF2CHF2propargyl 3-MeH MeSCF2CHF2Et 3-MeH MeSO2Mei-Pr 3-MeH MeSO2CF3t-Bu 3-Me5-ClCHF2CF3Me 3-MeH CHF2MeEt 3-MeH PhCF3i-Pr 3-MeH PhClt-Bu 3-MeH PhBrcyclopropyl3-Me5-Br2-pyridyl CF3Et 3-MeH 2-pyridyl Cli-Pr 3-Me5-Me2-ClPhCF3t-Bu 3-MeH 2-ClPhOCF3Me 3-MeH 2-ClPhBrEt 3-MeH 2-ClPhCli-Pr 3-Me5-Cl2-ClPhSCHF2t-Bu 3-MeH 2-BrPhCF3propargyl 3-MeH 2-MePhCF3Et 3-MeH 2-CNPhCF3i-Pr 3-MeH 2-FPh CF3t-Bu 3-Me5-Br2，6-F2PhCF3cyclopropyl3-MeH 2，4-F2PhCF3Et 3-MeH 2，5-F2PhCF3i-Pr 3-MeH 2-MeOPh CF3t-Bu 3-MeH 3-Cl-2-pyridylCF3
R3R4aR4bRvaRvbMe 3-MeH 3-Cl-2-pyridyl OCF3Et 3-Me5-Cl3-Cl-2-pyridyl Bri-Pr 3-MeH 3-Cl-2-pyridyl Clt-Bu 3-MeH 3-Cl-2-pyridyl SCHF2Me 3-MeH 3-F-2-pyridyl CF3propargyl 3-MeH 3-CF3-2-pyridyl CF3i-Pr 3-Me5-CN3-Me-2-pyridyl CF3t-Bu 3-MeH 3-Br-2-pyridyl CF3Me 3-MeH 3-Br-2-pyridyl OCF3Et 3-MeH 3-Br-2-pyridyl Bri-Pr 3-Me5-Br3-Br-2-pyridyl ClMe 6-MeH H CF3Et 6-Me4-MeH OCF3i-Pr 6-MeH H OCF3t-Bu 6-MeCl Me BrMe 6-MeH Et BrEt 6-MeH Me Cli-Pr 6-Me4-BrEt Clt-Bu 6-MeH Me Ipropargyl 6-MeH Me CF3cyclopropyl6-MeH Me OCF3i-Pr 6-Me4-ClMe CF3t-Bu 6-MeH Me SCF3Me 6-MeH Me SCHF2Et 6-MeH Me OCHF2i-Pr 6-Me4-CNMe CF3t-Bu 6-MeH Me C2F5propargyl 6-MeH Me C2F5cyclopropyl6-MeH Et CF3i-Pr 6-MeH n-Pr CF3t-Bu 6-Me4-Bri-Pr CF3Me 6-MeH Me SMeEt 6-MeH Me OMei-Pr 6-MeH Me OEtt-Bu 6-Me4-ClMe n-C3F7Me 6-MeH Me i-C3F7
R3R4aR4bRvaRvbEt 6-MeH Me Eti-Pr 6-MeH Me OCF2CHF2t-Bu 6-Me4-F Me SCF2CHF2propargyl 6-MeH Me SO2MeEt 6-MeH Me SO2CF3i-Pr 6-MeH CF3CF3t-Bu 6-Me4-ClCF3MeMe 6-MeH Ph CF3Et 6-MeH Ph Cli-Pr 6-MeH Ph Brt-Bu 6-MeH 2-pyridyl CF3cyclopropyl6-Me4-Br2-pyridyl ClEt 6-MeH 2-ClPh CF3i-Pr 6-MeH 2-ClPh OCF3t-Bu 6-Me4-Me2-ClPh BrMe 6-MeH 2-ClPh ClEt 6-MeH 2-ClPh SCHF2i-Pr 6-Me4-Cl2-BrPh CF3t-Bu 6-MeH 2-MePh CF3propargyl 6-MeH 2-CNPh CF3Et 6-MeH 2-FPh CF3i-Pr 6-MeH 2，6-F2Ph CF3t-Bu 6-Me4-Br2，4-F2Ph CF3cyclopropyl6-MeH 2，5-F2Ph CF3Et 6-MeH 2-MeOPhCF3i-Pr 6-MeH 3-Cl-2-pyridyl CF3t-Bu 6-MeH 3-Cl-2-pyridyl OCF3Me 6-MeH 3-Cl-2-pyridyl BrEt 6-Me4-Cl3-Cl-2-pyridyl Cli-Pr 6-MeH 3-Cl-2-pyridyl SCHF2t-Bu 6-Me4-CN3-F-2-pyridyl CF3Me 6-MeH 3-CF3-2-pyridyl CF3propargyl 6-MeH 3-Me-2-pyridyl CF3i-Pr 6-MeH 3-Br-2-pyridyl CF3t-Bu 6-MeH 3-Br-2-pyridyl OCF3Me 6-MeH 3-Br-2-pyridyl Br
R3R4aR4bRvaRvbEt 6-MeH 3-Br-2-pyridylClMe 3-ClH MeBrEt 3-Br5-MeEtBri-Pr 3-ClH MeClt-Bu 3-Cl5-ClEtClMe 3-ClH MeIEt 3-ClH MeCF3i-Pr 3-Cl5-BrMeOCF3t-Bu 3-ClH MeCF3propargyl 3-ClH MeSCF3cyclopropyl3-ClH MeSCHF2i-Pr 3-Cl5-ClMeOCHF2t-Bu 3-ClH MeCF3Me 3-FHMeC2F5Et 3-ClH MeC2F5i-Pr 3-Cl5-CNEtCF3t-Bu 3-ClH n-Pr CF3propargyl 3-ClH i-Pr CF3cyclopropyl3-ClH MeSMei-Pr 3-ClH MeOMet-Bu 3-Cl5-BrMeOEtMe 3-ClH Men-C3F7Et 3-BrH Mei-C3F7i-Pr 3-ClH MeEtt-Bu 3-Cl5-ClMeOCF2CHF2Me 3-ClH MeSCF2CHF2Et 3-ClH MeSO2Mei-Pr 3-ClH MeSO2CF3t-Bu 3-Cl5-F CF3CF3propargyl 3-ClH CF3MeEt 3-ClH PhCF3i-Pr 3-BrH PhClt-Bu 3-Cl5-ClPhBrMe 3-ClH 2-pyridyl CF3Et 3-CNH 2-pyridyl Cli-Pr 3-ClH 2-ClPhCF3
R3R4aR4bRvaRvbt-Bu 3-ClH 2-ClPh OCF3cyclopropyl3-Cl5-Br2-ClPh BrEt 3-ClH 2-ClPh Cli-Pr 3-ClH 2-ClPh OCF3t-Bu 3-ClH 2-BrPh CF3Me 3-F H 2-MePh CF3Et 3-ClH 2-CNPh CF3i-Pr 3-Cl5-Cl2-FPh CF3t-Bu 3-ClH 2，6-F2Ph CF3propargyl 3-ClH 2，4-F2Ph CF3Et 3-ClH 2，5-F2Ph CF3i-Pr 3-ClH 2-MeOPhCF3t-Bu 3-Cl5-Br3-Cl-2-pyridyl CF3cyclopropyl3-ClH 3-Cl-2-pyridyl OCF3Et 3-ClH 3-Cl-2-pyridyl Bri-Pr 3-BrH 3-Cl-2-pyridyl Clt-Bu 3-ClH 3-Cl-2-pyridyl SCHF2Me 3-ClH 3-F-2-pyridyl CF3Et 3-Cl5-Cl3-CF3-2-pyridyl CF3i-Pr 3-ClH 3-Me-2-pyridyl CF3t-Bu 3-I H 3-Br-2-pyridyl CF3Me 3-Cl5-Me3-Br-2-pyridyl OCF3propargyl 3-ClH 3-Br-2-pyridyl Bri-Pr 3-ClH 3-Br-2-pyridyl ClMe 6-ClH Et BrEt 6-Br4-MeMe Cli-Pr 6-ClH Et Clt-Bu 6-ClCl Me IMe 6-ClH Me CF3Et 6-ClH Me OCF3i-Pr 6-F 4-BrMe CF3t-Bu 6-ClH Me SCF3propargyl 6-ClH Me SCHF2cyclopropyl6-ClH Me OCHF2i-Pr 6-Cl4-ClMe CF3t-Bu 6-ClH Me C2F5
R3R4aR4bRvaRvbMe 6-ClH MeC2F5Et 6-ClH EtCF3i-Pr 6-I 4-CNn-Pr CF3t-Bu 6-ClH i-Pr CF3propargyl 6-ClH MeSMecyclopropyl6-ClH MeOMei-Pr 6-ClH MeOEtt-Bu 6-Cl4-BrMen-C3F7Me 6-ClH Mei-C3F7Et 6-F H MeEti-Pr 6-ClH MeOCF2CHF2t-Bu 6-Cl4-ClMeSCF2CHF2Me 6-ClH MeSO2MeEt 6-I H MeSO2CF3i-Pr 6-ClH CF3CF3t-Bu 6-Cl4-F CF3Mepropargyl 6-ClH PhCF3Et 6-ClH PhCli-Pr 6-ClH PhBrt-Bu 6-Cl4-Cl2-pyridyl CF3Me 6-ClH 2-pyridyl ClEt 6-ClH 2-ClPhCF3i-Pr 6-ClH 2-ClPhOCF3t-Bu 6-BrH 2-ClPhBrcyclopropyl6-Cl4-Br2-ClPhClEt 6-ClH 2-ClPhSCHF2i-Pr 6-ClH 2-BrPhCF3t-Bu 6-F 4-Me2-MePhCF3Me 6-ClH 2-CNPhCF3Et 6-ClH 2-FPh CF3i-Pr 6-CN4-Cl2，6-F2PhCF3t-Bu 6-ClH 2，4-F2PhCF3propargyl 6-ClH 2，5-F2PhCF3Et 6-ClH 2-MeOPh CF3i-Pr 6-ClH 3-Cl-2-pyridylCF3t-Bu 6-Cl4-Br3-Cl-2-pyridylOCF3
R3R4aR4bRvaRvbcyclopropyl6-ClH 3-Cl-2-pyridyl BrEt 6-F H 3-Cl-2-pyridyl Cli-Pr 6-ClH 3-Cl-2-pyridyl SCHF2t-Bu 6-ClH 3-F-2-pyridyl CF3Me 6-ClH 3-CF3-2-pyridyl CF3Et 6-Br4-Cl3-Me-2-pyridyl CF3i-Pr 6-ClH 3-Br-2-pyridyl CF3t-Bu 6-ClH 3-Br-2-pyridyl OCF3Me 6-ClH 3-Br-2-pyridyl Brpropargyl 6-ClH 3-Br-2-pyridyl ClTable 17 R3R4aR4bRvaRvbMe 3-MeH H CHF2Et 3-Me5-MeH CH2CF3i-Pr 3-MeH H CH2CF3t-Bu 3-Me5-ClMe CH2CF3Me 3-MeH Et CH2CF3Et 3-MeH Me CF2CHF2i-Pr 3-Me5-BrEt CHF2t-Bu 3-MeH Me CHF2propargyl 3-MeH Me CBrF2cyclopropyl3-MeH Me CH2Fi-Pr 3-Me5-ClMe CH2CF3t-Bu 3-MeH Me EtMe 3-Me5-CNMe n-PrEt 3-MeH Me CH2C2F5
R3R4aR4bRvaRvbi-Pr 3-MeH Me CH2CF3t-Bu 3-MeH Me CF3propargyl 3-MeH Me C2F5cyclopropyl3-MeH Et CHF2i-Pr 3-MeH n-Pr CH2CF3t-Bu 3-Me5-Bri-Pr CHF2Me 3-MeH Cl CH2CF3Et 3-MeH FCH2CF3i-Pr 3-MeH Me CH2Clt-Bu 3-Me5-ClMe CClF2Me 3-MeH Me CH2CH2ClEt 3-MeH Me n-C3F7i-Pr 3-MeH Me i-C3F7t-Bu 3-Me5-F Me Allylpropargyl 3-MeH Et CF2CHF2Et 3-MeH Et i-C3F7i-Pr 3-MeH n-Pr CF2CHF2t-Bu 3-Me5-Cli-Pr CF2CHF2Me 3-MeH CF3CF2CHF2Et 3-MeH CF3Mei-Pr 3-MeH OMe CH2CF3t-Bu 3-MeH HCH2CF3cyclopropyl3-Me5-BrHCH2CF3Et 3-MeH HC2F5i-Pr 3-Me5-MeHC2F5t-Bu 3-MeH HC2F5Me 3-MeH HCF2CHF2Et 3-MeH i-Pr CH2CF3i-Pr 3-Me5-ClHn-C3F7t-Bu 3-MeH Hi-C3F7propargyl 3-MeH Ph CH2CF3Et 3-MeH Ph CF2CHF2i-Pr 3-MeH Ph CHF2t-Bu 3-Me5-Br2-pyridylCH2CF3cyclopropyl3-MeH 2-pyridylCF2CHF2Et 3-MeH 2-ClPh CH2CF3
R3R4aR4bRvaRvbi-Pr 3-MeH 2-ClPh CF2CHF2t-Bu 3-MeH 2-ClPh CHF2Me 3-MeH 2-ClPh EtEt 3-Me5-Cl2-ClPh CBrF2i-Pr 3-MeH 2-BrPh CH2CF3t-Bu 3-MeH 2-MePh CF2CHF2Me 3-MeH 2-CNPh CH2CF3propargyl 3-MeH 2-FPh CH2CF3i-Pr 3-Me5-CN2，6-F2Ph CF2CHF2t-Bu 3-MeH 2，4-F2Ph CH2CF3Me 3-MeH 2，5-F2Ph CH2CF3Et 3-MeH 2-MeOPhCF2CHF2i-Pr 3-Me5-Br3-Cl-2-pyridyl CH2CF3t-Bu 3-MeH 3-Cl-2-pyridyl CF2CHF2Me 3-Me5-I 3-Cl-2-pyridyl CF3Et 3-MeH 3-Cl-2-pyridyl CHF2i-Pr 3-Me5-Me3-Cl-2-pyridyl CBrF2t-Bu 3-MeH 3-F-2-pyridyl CH2CF3propargyl 3-MeH 3-CF3-2-pyridyl CF2CHF2Et 3-Me5-Br3-Me-2-pyridyl CH2CF3i-Pr 3-MeH 3-Br-2-pyridyl CF3t-Bu 3-MeH 3-Br-2-pyridyl CH2CF3Me 3-MeH 3-Br-2-pyridyl CF2CHF2Et 3-MeH 3-Br-2-pyridyl CClF2Me 6-MeH H CHF2Et 6-Me4-MeH CH2CF3i-Pr 6-MeH H CH2CF3t-Bu 6-MeCl Me CH2CF3Me 6-MeH Et CH2CF3Et 6-MeH Me CF2CHF2i-Pr 6-Me4-BrEt CHF2t-Bu 6-MeH Me CHF2propargyl 6-MeH Me CBrF2cyclopropyl6-MeH Me CH2Fi-Pr 6-Me4-ClMe CH2CF3t-Bu 6-MeH Me Et
R3R4aR4bRvaRvbMe 6-MeH Me n-PrEt 6-MeH Me CH2C2F5i-Pr 6-Me4-CNMe CH2CF3t-Bu 6-MeH Me CF3propargyl 6-MeH Me C2F5cyclopropyl6-MeH Et CHF2i-Pr 6-MeH n-PrCH2CF3t-Bu 6-Me4-Bri-PrCHF2Me 6-MeH Cl CH2CF3Et 6-MeH F CH2CF3i-Pr 6-MeH Me CH2Clt-Bu 6-Me4-ClMe CClF2Me 6-MeH Me CH2CH2ClEt 6-MeH Me n-C3F7i-Pr 6-MeH Me i-C3F7t-Bu 6-Me4-F Me Allylpropargyl 6-MeH Me CF2CHF2Et 6-MeH Me i-C3F7i-Pr 6-MeH Me CF2CHF2t-Bu 6-Me4-ClMe CF2CHF2Me 6-MeH CF3CF2CHF2Et 6-MeH CF3Mei-Pr 6-MeH OMe CH2CF3t-Bu 6-MeH H CH2CF3cyclopropyl6-Me4-BrH CH2CF3Et 6-MeH H C2F5i-Pr 6-MeH H C2F5t-Bu 6-Me4-MeH C2F5Me 6-MeH H CF2CHF2Et 6-MeH H CH2CF3i-Pr 6-Me4-ClH n-C3F7t-Bu 6-MeH H i-C3F7propargyl 6-MeH H CH2CF3Et 6-MeH H CF2CHF2i-Pr 6-MeH H CHF2t-Bu 6-Me4-BrPh CH2CF3
R3R4aR4bRvaRvbcyclopropyl6-MeH Ph CF2CHF2Et 6-MeH Ph CH2CF3i-Pr 6-MeH 2-pyridyl CF2CHF2t-Bu 6-MeH 2-pyridyl CHF2Me 6-MeH 2-ClPh EtEt 6-Me4-Cl2-ClPh CBrF2i-Pr 6-MeH 2-ClPh CH2CF3t-Bu 6-Me4-CN2-ClPh CF2CHF2Me 6-MeH 2-ClPh CH2CF3propargyl 6-MeH 2-BrPh CH2CF3i-Pr 6-MeH 2-MePh CF2CHF2t-Bu 6-MeH 2-CNPh CH2CF3Me 6-MeH 2-FPh CH2CF3Et 6-MeH 2，6-F2Ph CF2CHF2i-Pr 6-Me4-Br2，4-F2Ph CH2CF3t-Bu 6-MeH 2，5-F2Ph CF2CHF2Me 6-Me4-I 2-MeOPhCF3Et 6-MeH 3-Cl-2-pyridyl CHF2i-Pr 6-MeH 3-Cl-2-pyridyl CBrF2t-Bu 6-MeH 3-Cl-2-pyridyl CH2CF3propargyl 6-MeH 3-Cl-2-pyridyl CF2CHF2Et 6-Me4-Br3-Cl-2-pyridyl CH2CF3i-Pr 6-MeH 3-F-2-pyridyl CF3t-Bu 6-MeH 3-CF3-2-pyridyl CH2CF3Me 6-MeH 3-Me-2-pyridyl CF2CHF2Et 6-MeH 3-Br-2-pyridyl CClF2i-Pr 6-Me4-Cl3-Br-2-pyridyl CH2CF3t-Bu 6-MeH 3-Br-2-pyridyl CF3i-Pr 6-MeH 3-Br-2-pyridyl CF2CHF2Me 3-ClH H CHF2Et 3-Br5-MeH CH2CF3i-Pr 3-ClH H CH2CF3t-Bu 3-Cl5-ClMe CH2CF3Me 3-ClH Et CH2CF3Et 3-ClH Me CF2CHF2i-Pr 3-Cl5-BrEt CHF2
R3R4aR4bRvaRvbt-Bu 3-ClH Me CHF2propargyl 3-ClH Me CBrF2cyclopropyl3-ClH Me CH2Fi-Pr 3-Cl5-ClMe CH2CF3t-Bu 3-ClH Me EtMe 3-F H Me n-PrEt 3-ClH Me CH2C2F5i-Pr 3-Cl5-CNMe CH2CF3t-Bu 3-ClH Me CF3propargyl 3-ClH Me C2F5cyclopropyl3-ClH Et CHF2i-Pr 3-ClH n-PrCH2CF3t-Bu 3-Cl5-Bri-PrCHF2Me 3-ClH Cl CH2CF3Et 3-BrH F CH2CF3i-Pr 3-ClH Me CH2Clt-Bu 3-Cl5-ClMe CClF2Me 3-ClH Me CH2CH2ClEt 3-ClH Me n-C3F7i-Pr 3-ClH Me i-C3F7t-Bu 3-Cl5-F Me Allylpropargyl 3-ClH Me CF2CHF2Et 3-ClH Me i-C3F7i-Pr 3-BrH Me CF2CHF2t-Bu 3-Cl5-ClMe CF2CHF2Me 3-ClH CF3CF2CHF2Et 3-CNH CF3Mei-Pr 3-ClH OMe CH2CF3t-Bu 3-ClH H CH2CF3cyclopropyl3-Cl5-BrH CH2CF3Et 3-ClH H C2F5i-Pr 3-ClH H C2F5t-Bu 3-ClH H C2F5Me 3-F H H CF2CHF2Et 3-ClH H CH2CF3i-Pr 3-Cl5-ClH n-C3F7
R3R4aR4bRvaRvbt-Bu 3-ClH H i-C3F7propargyl3-ClH H CH2CF3Et 3-ClH H CF2CHF2i-Pr 3-ClH H CHF2t-Bu 3-Cl5-BrPhCH2CF3cyclopropyl 3-ClH PhCF2CHF2Et 3-ClH PhCH2CF3i-Pr 3-BrH 2-pyridyl CF2CHF2t-Bu 3-ClH 2-pyridyl CHF2Me 3-ClH 2-ClPhEtEt 3-Cl5-Cl2-ClPhCBrF2i-Pr 3-ClH 2-ClPhCH2CF3t-Bu 3-I H 2-ClPhCF2CHF2Me 3-Cl5-Me2-ClPhCH2CF3propargyl3-ClH 2-BrPhCH2CF3i-Pr 3-ClH 2-MePhCF2CHF2t-Bu 3-Cl5-CN2-CNPhCH2CF3Me 3-ClH 2-FPh CH2CF3Et 3-ClH 2，6-F2PhCF2CHF2i-Pr 3-Cl5-Br2，4-F2PhCH2CF3t-Bu 3-F H 2，5-F2PhCF2CHF2Me 3-Cl5-I 2-MeOPh CF3Et 3-ClH 3-Cl-2-pyridylCHF2i-Pr 3-CNH 3-Cl-2-pyridylCBrF2t-Bu 3-ClH 3-Cl-2-pyridylCH2CF3propargyl3-ClH 3-Cl-2-pyridylCF2CHF2Et 3-Cl5-Br3-Cl-2-pyridylCH2CF3i-Pr 3-ClH 3-F-2-pyridyl CF3t-Bu 3-BrH 3-CF3-2-pyridyl CH2CF3Me 3-ClH 3-Me-2-pyridylCF2CHF2Et 3-ClH 3-Br-2-pyridylCClF2i-Pr 3-Cl5-Cl3-Br-2-pyridylCH2CF3t-Bu 3-ClH 3-Br-2-pyridylCF3i-Pr 3-ClH 3-Br-2-pyridylCF2CHF2Me 6-ClH EtCHF2Et 6-Br4-MeMeCH2CF3
R3R4aR4bRvaRvbi-Pr 6-ClH Et CH2CF3t-Bu 6-ClCl Me CH2CF3Me 6-ClH Me CH2CF3Et 6-ClH Me CF2CHF2i-Pr 6-F 4-BrMe CHF2t-Bu 6-ClH Me CHF2propargyl 6-ClH Me CBrF2cyclopropyl6-ClH Me CH2Fi-Pr 6-Cl4-ClMe CH2CF3t-Bu 6-ClH Me EtMe 6-ClH Me n-PrEt 6-ClH Et CH2C2F5i-Pr 6-I 4-CNn-Pr CH2CF3t-Bu 6-ClH i-Pr CF3propargyl 6-ClH Cl C2F5cyclopropyl6-ClH F CHF2i-Pr 6-ClH Me CH2CF3t-Bu 6-Cl4-BrMe CHF2Me 6-ClH Me CH2CF3Et 6-F H Me CH2CF3i-Pr 6-ClH Me CH2Clt-Bu 6-Cl4-ClMe CClF2Me 6-ClH Me CH2CH2ClEt 6-I H Me n-C3F7i-Pr 6-ClH Me i-C3F7t-Bu 6-Cl4-F Me Allylpropargyl 6-ClH CF3CF2CHF2Et 6-ClH CF3i-C3F7i-Pr 6-ClH OMeCF2CHF2t-Bu 6-Cl4-ClH CF2CHF2Me 6-ClH H CF2CHF2Et 6-ClH H Mei-Pr 6-ClH H CH2CF3t-Bu 6-BrH H CH2CF3cyclopropyl6-Cl4-BrH CH2CF3Et 6-ClH H C2F5
R3R4aR4bRvaRvbi-Pr 6-ClH H C2F5t-Bu 6-F 4-MeH C2F5Me 6-ClH H CF2CHF2Et 6-ClH H CH2CF3i-Pr 6-CN4-ClH n-C3F7t-Bu 6-ClH Phi-C3F7propargyl6-ClH PhCH2CF3Et 6-ClH PhCF2CHF2i-Pr 6-ClH 2-pyridyl CHF2t-Bu 6-Cl4-Br2-pyridyl CH2CF3cyclopropyl 6-ClH 2-ClPhCF2CHF2Et 6-F H 2-ClPhCH2CF3i-Pr 6-ClH 2-ClPhCF2CHF2t-Bu 6-ClH 2-ClPhCHF2Me 6-ClH 2-ClPhEtEt 6-Br4-Cl2-BrPhCBrF2i-Pr 6-ClH 2-MePhCH2CF3t-Bu 6-ClH 2-CNPhCF2CHF2Me 6-ClH 2-FPh CH2CF3propargyl6-ClH 2，6-F2PhCH2CF3i-Pr 6-BrH 2，4-F2PhCF2CHF2t-Bu 6-Cl4-CN2，5-F2PhCH2CF3Me 6-ClH 2-MeOPh CH2CF3Et 6-ClH 3-Cl-2-pyridylCF2CHF2i-Pr 6-Cl4-Br3-Cl-2-pyridylCH2CF3t-Bu 6-CNH 3-Cl-2-pyridylCF2CHF2Me 6-Cl4-I 3-Cl-2-pyridylCF3Et 6-ClH 3-Cl-2-pyridylCHF2i-Pr 6-BrH 3-F-2-pyridyl CBrF2t-Bu 6-ClH 3-CF3-2-pyridyl CH2CF3propargyl6-ClH 3-Me-2-pyridylCF2CHF2Et 6-Cl4-Br3-Br-2-pyridylCH2CF3i-Pr 6-ClH 3-Br-2-pyridylCF3t-Bu 6-ClH 3-Br-2-pyridylCH2CF3Me 6-ClH 3-Br-2-pyridylCF2CHF2
Table 18 R3R4aR4bRvaRvbMe 3-Me H H CHF2Et 3-Me 5-Me H CH2CF3i-Pr 3-Me H H CH2CF3t-Bu 3-Me 5-Cl Me CH2CF3Me 3-Me H Et CH2CF3Et 3-Me H Me CF2CHF2i-Pr 3-Me 5-Br Et CHF2t-Bu 3-Me H Me CHF2propargyl 3-Me H Me CBrF2cyclopropyl3-Me H Me CH2Fi-Pr 3-Me 5-Cl Me CH2CF3t-Bu 3-Me H Me EtMe 3-Me 5-CN Me n-PrEt 3-Me H Me CH2C2F5i-Pr 3-Me H Me CH2CF3t-Bu 3-Me H Me CF3propargyl 3-Me H Me C2F5cyclopropyl3-Me H Et CHF2i-Pr 3-Me H n-PrCH2CF3t-Bu 3-Me 5-Br i-PrCHF2Me 3-Me H Cl CH2CF3Et 3-Me H F CH2CF3i-Pr 3-Me H Me CH2Clt-Bu 3-Me 5-Cl Me CClF2Me 3-Me H Me CH2CH2ClEt 3-Me H Me n-C3F7
R3R4aR4bRvaRvbi-Pr 3-Me H Me i-C3F7t-Bu 3-Me 5-F Me Allylpropargyl 3-Me H Et CF2CHF2Et 3-Me H Et i-C3F7i-Pr 3-Me H n-Pr CF2CHF2t-Bu 3-Me 5-Cli-Pr CF2CHF2Me 3-Me H CF3CF2CHF2Et 3-Me H CF3Mei-Pr 3-Me H OMe CH2CF3t-Bu 3-Me H HCH2CF3cyclopropyl3-Me 5-BrHCH2CF3Et 3-Me H HC2F5i-Pr 3-Me 5-MeHC2F5t-Bu 3-Me H HC2F5Me 3-Me H HCF2CHF2Et 3-Me H i-Pr CH2CF3i-Pr 3-Me 5-ClHn-C3F7t-Bu 3-Me H Hi-C3F7propargyl 3-Me H Ph CH2CF3Et 3-Me H Ph CF2CHF2i-Pr 3-Me H Ph CHF2t-Bu 3-Me 5-Br2-pyridylCH2CF3cyclopropyl3-Me H 2-pyridylCF2CHF2Et 3-Me H 2-ClPh CH2CF3i-Pr 3-Me H 2-ClPh CF2CHF2t-Bu 3-Me H 2-ClPh CHF2Me 3-Me H 2-ClPh EtEt 3-Me 5-Cl2-ClPh CBrF2i-Pr 3-Me H 2-BrPh CH2CF3t-Bu 3-Me H 2-MePh CF2CHF2Me 3-Me H 2-CNPh CH2CF3propargyl 3-Me H 2-FPhCH2CF3i-Pr 3-Me 5-CN2，6-F2Ph CF2CHF2t-Bu 3-Me H 2，4-F2Ph CH2CF3Me 3-Me H 2，5-F2Ph CH2CF3Et 3-Me H 2-MeOPh CF2CHF2
R3R4aR4bRvaRvbi-Pr 3-Me5-Br3-Cl-2-pyridyl CH2CF3t-Bu 3-MeH 3-Cl-2-pyridyl CF2CHF2Me 3-Me5-I 3-Cl-2-pyridyl CF3Et 3-MeH 3-Cl-2-pyridyl CHF2i-Pr 3-Me5-Me3-Cl-2-pyridyl CBrF2t-Bu 3-MeH 3-F-2-pyridyl CH2CF3propargyl 3-MeH 3-CF3-2-pyridyl CF2CHF2Et 3-Me5-Br3-Me-2-pyridyl CH2CF3i-Pr 3-MeH 3-Br-2-pyridyl CF3t-Bu 3-MeH 3-Br-2-pyridyl CH2CF3Me 3-MeH 3-Br-2-pyridyl CF2CHF2Et 3-MeH 3-Br-2-pyridyl CClF2Me 6-MeH H CHF2Et 6-Me4-MeH CH2CF3i-Pr 6-MeH H CH2CF3t-Bu 6-MeCl Me CH2CF3Me 6-MeH Et CH2CF3Et 6-MeH Me CF2CHF2i-Pr 6-Me4-BrEt CHF2t-Bu 6-MeH Me CHF2propargyl 6-MeH Me CBrF2cyclopropyl6-MeH Me CH2Fi-Pr 6-Me4-ClMe CH2CF3t-Bu 6-MeH Me EtMe 6-MeH Me n-PrEt 6-MeH Me CH2C2F5i-Pr 6-Me4-CNMe CH2CF3t-Bu 6-MeH Me CF3propargyl 6-MeH Me C2F5cyclopropyl6-MeH Et CHF2i-Pr 6-MeH n-Pr CH2CF3t-Bu 6-Me4-Bri-Pr CHF2Me 6-MeH Cl CH2CF3Et 6-MeH F CH2CF3i-Pr 6-MeH Me CH2Clt-Bu 6-Me4-ClMe CClF2
R3R4aR4bRvaRvbMe 6-Me H Me CH2CH2ClEt 6-Me H Me n-C3F7i-Pr 6-Me H Me i-C3F7t-Bu 6-Me 4-F Me Allylpropargyl6-Me H Me CF2CHF2Et 6-Me H Me i-C3F7i-Pr 6-Me H Me CF2CHF2t-Bu 6-Me 4-ClMe CF2CHF2Me 6-Me H CF3CF2CHF2Et 6-Me H CF3Mei-Pr 6-Me H OMe CH2CF3t-Bu 6-Me H HCH2CF3cyclopropyl 6-Me 4-BrHCH2CF3Et 6-Me H HC2F5i-Pr 6-Me H HC2F5t-Bu 6-Me 4-MeHC2F5Me 6-Me H HCF2CHF2Et 6-Me H HCH2CF3i-Pr 6-Me 4-ClHn-C3F7t-Bu 6-Me H Hi-C3F7propargyl6-Me H HCH2CF3Et 6-Me H HCF2CHF2i-Pr 6-Me H HCHF2t-Bu 6-Me 4-BrPh CH2CF3cyclopropyl 6-Me H Ph CF2CHF2Et 6-Me H Ph CH2CF3i-Pr 6-Me H 2-pyridylCF2CHF2t-Bu 6-Me H 2-pyridylCHF2Me 6-Me H 2-ClPh EtEt 6-Me 4-Cl2-ClPh CBrF2i-Pr 6-Me H 2-ClPh CH2CF3t-Bu 6-Me 4-CN2-ClPh CF2CHF2Me 6-Me H 2-ClPh CH2CF3propargyl6-Me H 2-BrPh CH2CF3i-Pr 6-Me H 2-MePh CF2CHF2t-Bu 6-Me H 2-CNPh CH2CF3
R3R4aR4bRvaRvbMe 6-MeH 2-FPh CH2CF3Et 6-MeH 2，6-F2PhCF2CHF2i-Pr6-Me4-Br 2，4-F2PhCH2CF3t-Bu6-MeH 2，5-F2PhCF2CHF2Me 6-Me4-I2-MeOPh CF3Et 6-MeH 3-Cl-2-pyridylCHF2i-Pr6-MeH 3-Cl-2-pyridylCBrF2t-Bu6-MeH 3-Cl-2-pyridylCH2CF3propargyl 6-MeH 3-Cl-2-pyridylCF2CHF2Et 6-Me4-Br 3-Cl-2-pyridylCH2CF3i-Pr6-MeH 3-F-2-pyridyl CF3t-Bu6-MeH 3-CF3-2-pyridyl CH2CF3Me 6-MeH 3-Me-2-pyridylCF2CHF2Et 6-MeH 3-Br-2-pyridylCClF2i-Pr6-Me4-Cl 3-Br-2-pyridylCH2CF3t-Bu6-MeH 3-Br-2-pyridylCF3i-Pr6-MeH 3-Br-2-pyridylCF2CHF2Me 3-ClH H CHF2Et 3-Br5-Me H CH2CF3i-Pr3-ClH H CH2CF3t-Bu3-Cl5-Cl MeCH2CF3Me 3-ClH EtCH2CF3Et 3-ClH MeCF2CHF2i-Pr3-Cl5-Br EtCHF2t-Bu3-ClH MeCHF2propargyl 3-ClH MeCBrF2cyclopropyl 3-ClH MeCH2Fi-Pr3-Cl5-Cl MeCH2CF3t-Bu3-ClH MeEtMe 3-F H Men-PrEt 3-ClH MeCH2C2F5i-Pr3-Cl5-CN MeCH2CF3t-Bu3-ClH MeCF3propargyl 3-ClH MeC2F5cyclopropyl 3-ClH EtCHF2i-Pr3-ClH n-Pr CH2CF3
R3R4aR4bRvaRvbt-Bu 3-Cl 5-Br i-Pr CHF2Me 3-Cl H Cl CH2CF3Et 3-Br H FCH2CF3i-Pr 3-Cl H Me CH2Clt-Bu 3-Cl 5-Cl Me CClF2Me 3-Cl H Me CH2CH2ClEt 3-Cl H Me n-C3F7i-Pr 3-Cl H Me i-C3F7t-Bu 3-Cl 5-F Me Allylpropargyl 3-Cl H Me CF2CHF2Et 3-Cl H Me i-C3F7i-Pr 3-Br H Me CF2CHF2t-Bu 3-Cl 5-Cl Me CF2CHF2Me 3-Cl H CF3CF2CHF2Et 3-CN H CF3Mei-Pr 3-Cl H OMe CH2CF3t-Bu 3-Cl H HCH2CF3cyclopropyl3-Cl 5-Br HCH2CF3Et 3-Cl H HC2F5i-Pr 3-Cl H HC2F5t-Bu 3-Cl H HC2F5Me 3-F H HCF2CHF2Et 3-Cl H HCH2CF3i-Pr 3-Cl 5-Cl Hn-C3F7t-Bu 3-Cl H Hi-C3F7propargyl 3-Cl H HCH2CF3Et 3-Cl H HCF2CHF2i-Pr 3-Cl H HCHF2t-Bu 3-Cl 5-Br Ph CH2CF3cyclopropyl3-Cl H Ph CF2CHF2Et 3-Cl H Ph CH2CF3i-Pr 3-Br H 2-pyridylCF2CHF2t-Bu 3-Cl H 2-pyridylCHF2Me 3-Cl H 2-ClPh EtEt 3-Cl 5-Cl 2-ClPh CBrF2i-Pr 3-Cl H 2-ClPh CH2CF3
R3R4aR4bRvaRvbt-Bu 3-IH 2-ClPhCF2CHF2Me 3-Cl 5-Me 2-ClPhCH2CF3propargyl 3-Cl H 2-BrPhCH2CF3i-Pr 3-Cl H 2-MePhCF2CHF2t-Bu 3-Cl 5-CN 2-CNPhCH2CF3Me 3-Cl H 2-FPh CH2CF3Et 3-Cl H 2，6-F2PhCF2CHF2i-Pr 3-Cl 5-Br 2，4-F2PhCH2CF3t-Bu 3-FH 2，5-F2PhCF2CHF2Me 3-Cl 5-I2-MeOPh CF3Et 3-Cl H 3-Cl-2-pyridylCHF2i-Pr 3-CN H 3-Cl-2-pyridylCBrF2t-Bu 3-Cl H 3-Cl-2-pyridylCH2CF3propargyl 3-Cl H 3-Cl-2-pyridylCF2CHF2Et 3-Cl 5-Br 3-Cl-2-pyridylCH2CF3i-Pr 3-Cl H 3-F-2-pyridyl CF3t-Bu 3-Br H 3-CF3-2-pyridyl CH2CF3Me 3-Cl H 3-Me-2-pyridylCF2CHF2Et 3-Cl H 3-Br-2-PyridylCClF2i-Pr 3-Cl 5-Cl 3-Br-2-pyridylCH2CF3t-Bu 3-Cl H 3-Br-2-pyridylCF3i-Pr 3-Cl H 3-Br-2-pyridylCF2CHF2Me 6-Cl H EtCHF2Et 6-Br 4-Me MeCH2CF3i-Pr 6-Cl H EtCH2CF3t-Bu 6-Cl Cl MeCH2CF3Me 6-Cl H MeCH2CF3Et 6-Cl H MeCF2CHF2i-Pr 6-F4-Br MeCHF2t-Bu 6-Cl H MeCHF2propargyl 6-Cl H MeCBrF2cyclopropyl6-Cl H MeCH2Fi-Pr 6-Cl 4-Cl MeCH2CF3t-Bu 6-Cl H MeEtMe 6-Cl H Men-PrEt 6-Cl H EtCH2C2F5
R3R4aR4bRvaRvbi-Pr 6-I4-CN n-Pr CH2CF3t-Bu 6-Cl H i-Pr CF3propargyl 6-Cl H Cl C2F5cyclopropyl6-Cl H FCHF2i-Pr 6-Cl H Me CH2CF3t-Bu 6-Cl 4-Br Me CHF2Me 6-Cl H Me CH2CF3Et 6-FH Me CH2CF3i-Pr 6-Cl H Me CH2Clt-Bu 6-Cl 4-Cl Me CClF2Me 6-Cl H Me CH2CH2ClEt 6-IH Me n-C3F7i-Pr 6-Cl H Me i-C3F7t-Bu 6-Cl 4-F Me Allylpropargyl 6-Cl H CF3CF2CHF2Et 6-Cl H CF3i-C3F7i-Pr 6-Cl H OMe CF2CHF2t-Bu 6-Cl 4-Cl HCF2CHF2Me 6-Cl H HCF2CHF2Et 6-Cl H HMei-Pr 6-Cl H HCH2CF3t-Bu 6-Br H HCH2CF3cyclopropyl6-Cl 4-Br HCH2CF3Et 6-Cl H HC2F5i-Pr 6-Cl H HC2F5t-Bu 6-F4-Me HC2F5Me 6-Cl H HCF2CHF2Et 6-Cl H HCH2CF3i-Pr 6-CN 4-Cl Hn-C3F7t-Bu 6-Cl H Ph i-C3F7propargyl 6-Cl H Ph CH2CF3Et 6-Cl H Ph CF2CHF2i-Pr 6-Cl H 2-pyridylCHF2t-Bu 6-Cl 4-Br 2-pyridylCH2CF3cyclopropyl6-Cl H 2-ClPh CF2CHF2Et 6-FH 2-ClPh CH2CF3
R3R4aR4bRvaRvbi-Pr 6-ClH 2-ClPh CF2CHF2t-Bu 6-ClH 2-ClPh CHF2Me 6-ClH 2-ClPh EtEt 6-Br4-Cl2-BrPh CBrF2i-Pr 6-ClH 2-MePh CH2CF3t-Bu 6-ClH 2-CNPh CF2CHF2Me 6-ClH 2-FPh CH2CF3propargyl 6-ClH 2，6-F2Ph CH2CF3i-Pr 6-BrH 2，4-F2Ph CF2CHF2t-Bu 6-Cl4-CN2，5-F2Ph CH2CF3Me 6-ClH 2-MeOPhCH2CF3Et 6-ClH 3-Cl-2-pyridyl CF2CHF2i-Pr 6-Cl4-Br3-Cl-2-pyridyl CH2CF3t-Bu 6-CNH 3-Cl-2-pyridyl CF2CHF2Me 6-Cl4-I 3-Cl-2-pyridyl CF3Et 6-ClH 3-Cl-2-pyridyl CHF2i-Pr 6-BrH 3-F-2-pyridyl CBrF2t-Bu 6-ClH 3-CF3-2-pyridyl CH2CF3propargyl 6-ClH 3-Me-2-pyridyl CF2CHF2Et 6-Cl4-Br3-Br-2-pyridyl CH2CF3i-Pr 6-ClH 3-Br-2-pyridyl CF3t-Bu 6-ClH 3-Br-2-pyridyl CH2CF3Me 6-ClH 3-Br-2-pyridyl CF2CHF2Table 19 R3R4aR4bRvaRvbMe 3-MeH H CHF2
R3R4aR4bRvaRvbEt 3-Me5-MeH CH2CF3i-Pr 3-MeH H CH2CF3t-Bu 3-Me5-ClMe CH2CF3Me 3-MeH Et CH2CF3Et 3-MeH Me CF2CHF2i-Pr 3-Me5-BrEt CHF2t-Bu 3-MeH Me CHF2propargyl 3-MeH Me CBrF2cyclopropyl3-MeH Me CH2Fi-Pr 3-Me5-ClMe CH2CF3t-Bu 3-MeH Me EtMe 3-Me5-CNMe n-PrEt 3-MeH Me CH2C2F5i-Pr 3-MeH Me CH2CF3t-Bu 3-MeH Me CF3propargyl 3-MeH Me C2F5cyclopropyl3-MeH Et CHF2i-Pr 3-MeH n-PrCH2CF3t-Bu 3-Me5-Bri-PrCHF2Me 3-MeH Cl CH2CF3Et 3-MeH F CH2CF3i-Pr 3-MeH Me CH2Clt-Bu 3-Me5-ClMe CClF2Me 3-MeH Me CH2CH2ClEt 3-MeH Me n-C3F7i-Pr 3-MeH Me i-C3F7t-Bu 3-Me5-F Me Allylpropargyl 3-MeH Et CF2CHF2Et 3-MeH Et i-C3F7i-Pr 3-MeH n-PrCF2CHF2t-Bu 3-Me5-Cli-PrCF2CHF2Me 3-MeH CF3CF2CHF2Et 3-MeH CF3Mei-Pr 3-MeH OMe CH2CF3t-Bu 3-MeH H CH2CF3cyclopropyl3-Me5-BrH CH2CF3
R3R4aR4bRvaRvbEt 3-MeH H C2F5i-Pr 3-Me5-MeH C2F5t-Bu 3-MeH H C2F5Me 3-MeH H CF2CHF2Et 3-MeH i-Pr CH2CF3i-Pr 3-Me5-ClH n-C3F7t-Bu 3-MeH H i-C3F7propargyl 3-MeH Ph CH2CF3Et 3-MeH Ph CF2CHF2i-Pr 3-MeH Ph CHF2t-Bu 3-Me5-Br2-pyridyl CH2CF3cyclopropyl3-MeH 2-pyridyl CF2CHF2Et 3-MeH 2-ClPh CH2CF3i-Pr 3-MeH 2-ClPh CF2CHF2t-Bu 3-MeH 2-ClPh CHF2Me 3-MeH 2-ClPh EtEt 3-Me5-Cl2-ClPh CBrF2i-Pr 3-MeH 2-BrPh CH2CF3t-Bu 3-MeH 2-MePh CF2CHF2Me 3-MeH 2-CNPh CH2CF3propargyl 3-MeH 2-FPh CH2CF3i-Pr 3-Me5-CN2，6-F2Ph CF2CHF2t-Bu 3-MeH 2，4-F2Ph CH2CF3Me 3-MeH 2，5-F2Ph CH2CF3Et 3-MeH 2-MeOPhCF2CHF2i-Pr 3-Me5-Br3-Cl-2-pyridyl CH2CF3t-Bu 3-MeH 3-Cl-2-pyridyl CF2CHF2Me3-Me5-I 3-Cl-2-pyridyl CF3Et 3-MeH 3-Cl-2-pyridyl CHF2i-Pr 3-Me5-Me3-Cl-2-pyridyl CBrF2t-Bu 3-MeH 3-F-2-pyridyl CH2CF3propargyl 3-MeH 3-CF3-2-pyridyl CF2CHF2Et 3-Me5-Br3-Me-2-pyridyl CH2CF3i-Pr 3-MeH 3-Br-2-pyridyl CF3t-Bu 3-MeH 3-Br-2-pyridyl CH2CF3Me 3-MeH 3-Br-2-pyridyl CF2CHF2
R3R4aR4bRvaRvbEt 3-MeH 3-Br-2-pyridylCClF2Me 6-MeH H CHF2Et 6-Me4-MeH CH2CF3i-Pr 6-MeH H CH2CF3t-Bu 6-MeCl MeCH2CF3Me 6-MeH EtCH2CF3Et 6-MeH MeCF2CHF2i-Pr 6-Me4-BrEtCHF2t-Bu 6-MeH MeCHF2propargyl 6-MeH MeCBrF2cyclopropyl6-MeH MeCH2Fi-Pr 6-Me4-ClMeCH2CF3t-Bu 6-MeH MeEtMe 6-MeH Men-PrEt 6-MeH MeCH2C2F5i-Pr 6-Me4-CNMeCH2CF3t-Bu 6-MeH MeCF3propargyl 6-MeH MeC2F5cyclopropyl6-MeH EtCHF2i-Pr 6-MeH n-Pr CH2CF3t-Bu 6-Me4-Bri-Pr CHF2Me 6-MeH ClCH2CF3Et 6-MeH F CH2CF3i-Pr 6-MeH MeCH2Clt-Bu 6-Me4-ClMeCClF2Me 6-MeH MeCH2CH2ClEt 6-MeH Men-C3F7i-Pr 6-MeH Mei-C3F7t-Bu 6-Me4-F MeAllylpropargyl 6-MeH MeCF2CHF2Et 6-MeH Mei-C3F7i-Pr 6-MeH MeCF2CHF2t-Bu 6-Me4-ClMeCF2CHF2Me 6-MeH CF3CF2CHF2Et 6-MeH CF3Mei-Pr 6-MeH OMe CH2CF3
R3R4aR4bRvaRvbt-Bu 6-MeH H CH2CF3cyclopropyl6-Me4-BrH CH2CF3Et 6-MeH H C2F5i-Pr 6-MeH H C2F5t-Bu 6-Me4-MeH C2F5Me 6-MeH H CF2CHF2Et 6-MeH H CH2CF3i-Pr 6-Me4-ClH n-C3F7t-Bu 6-MeH H i-C3F7propargyl 6-MeH H CH2CF3Et 6-MeH H CF2CHF2i-Pr 6-MeH H CHF2t-Bu 6-Me4-BrPhCH2CF3cyclopropyl6-MeH PhCF2CHF2Et 6-MeH PhCH2CF3i-Pr 6-MeH 2-pyridyl CF2CHF2t-Bu 6-MeH 2-pyridyl CHF2Me 6-MeH 2-ClPhEtEt 6-Me4-Cl2-ClPhCBrF2i-Pr 6-MeH 2-ClPhCH2CF3t-Bu 6-Me4-CN2-ClPhCF2CHF2Me 6-MeH 2-ClPhCH2CF3propargyl 6-MeH 2-BrPhCH2CF3i-Pr 6-MeH 2-MePhCF2CHF2t-Bu 6-MeH 2-CNPhCH2CF3Me 6-MeH 2-FPh CH2CF3Et 6-MeH 2，6-F2PhCF2CHF2i-Pr 6-Me4-Br2，4-F2PhCH2CF3t-Bu 6-MeH 2，5-F2PhCF2CHF2Me 6-Me4-I 2-MeOPh CF3Et 6-MeH 3-Cl-2-pyridylCHF2i-Pr 6-MeH 3-Cl-2-pyridylCBrF2t-Bu 6-MeH 3-Cl-2-pyridylCH2CF3propargyl 6-MeH 3-Cl-2-pyridylCF2CHF2Et 6-Me4-Br3-Cl-2-pyridylCH2CF3i-Pr 6-MeH 3-F-2-pyridyl CF3
R3R4aR4bRvaRvbt-Bu 6-MeH 3-CF3-2-pyridyl CH2CF3Me 6-MeH 3-Me-2-pyridyl CF2CHF2Et 6-MeH 3-Br-2-pyridyl CClF2i-Pr 6-Me4-Cl3-Br-2-puridyl CH2CF3t-Bu 6-MeH 3-Br-2-pyridyl CF3i-Pr 6-MeH 3-Br-2-pyridyl CF2CHF2Me 3-ClH H CHF2Et 3-Br5-MeH CH2CF3i-Pr 3-ClH H CH2CF3t-Bu 3-Cl5-ClMe CH2CF3Me 3-ClH Et CH2CF3Et 3-ClH Me CF2CHF2i-Pr 3-Cl5-BrEt CHF2t-Bu 3-ClH Me CHF2proparyl 3-ClH Me CBrF2cyclopropyl3-ClH Me CH2Fi-Pr 3-Cl5-ClMe CH2CF3t-Bu 3-ClH Me EtMe 3-F H Me n-PrEt 3-ClH Me CH2C2F5i-Pr 3-Cl5-CNMe CH2CF3t-Bu 3-ClH Me CF3propargyl 3-ClH Me C2F5cyclopropyl3-ClH Et CHF2i-Pr 3-ClH n-Pr CH2CF3t-Bu 3-Cl5-Bri-Pr CHF2Me 3-ClH Cl CH2CF3Et 3-BrH F CH2CF3i-Pr 3-ClH Me CH2Clt-Bu 3-Cl5-ClMe CClF2Me 3-ClH Me CH2CH2ClEt 3-ClH Me n-C3F7i-Pr 3-ClH Me i-C3F7t-Bu 3-Cl5-F Me Allylpropargyl 3-ClH Me CF2CHF2Et 3-ClH Me i-C3F7
R3R4aR4bRvaRvbi-Pr 3-BrH MeCF2CHF2t-Bu 3-Cl5-ClMeCF2CHF2Me 3-ClH CF3CF2CHF2Et 3-CNH CF3Mei-Pr 3-ClH OMe CH2CF3t-Bu 3-ClH H CH2CF3cyclopropyl3-Cl5-BrH CH2CF3Et 3-ClH H C2F5i-Pr 3-ClH H C2F5t-Bu 3-ClH H C2F5Me 3-F H H CF2CHF2Et 3-ClH H CH2CF3i-Pr 3-Cl5-ClH n-C3F7t-Bu 3-ClH H i-C3F7propargyl 3-ClH H CH2CF3Et 3-ClH H CF2CHF2i-Pr 3-ClH H CHF2t-Bu 3-Cl5-BrPhCH2CF3cyclopropyl3-ClH PhCF2CHF2Et 3-ClH PhCH2CF3i-Pr 3-BrH 2-pyridyl CF2CHF2t-Bu 3-ClH 2-pyridyl CHF2Me 3-ClH 2-ClPhEtEt 3-Cl5-Cl2-ClPhCBrF2i-Pr 3-ClH 2-ClPhCH2CF3t-Bu 3-I H 2-ClPhCF2CHF2Me 3-Cl5-Me2-ClPhCH2CF3propargyl 3-ClH 2-BrPhCH2CF3i-Pr 3-ClH 2-MePhCF2CHF2t-Bu 3-Cl5-CN2-CNPhCH2CF3Me 3-ClH 2-FPh CH2CF3Et 3-ClH 2，6-F2PhCF2CHF2i-Pr 3-Cl5-Br2，4-F2PhCH2CF3t-Bu 3-F H 2，5-F2PhCF2CHF2Me 3-Cl5-I 2-MeOPh CF3Et 3-ClH 3-Cl-2-pyridylCHF2
R3R4aR4bRvaRvbi-Pr 3-CNH 3-Cl-2-pyridyl CBrF2t-Bu 3-ClH 3-Cl-2-pyridyl CH2CF3propargyl 3-ClH 3-Cl-2-pyridyl CF2CHF2Et 3-Cl5-Br3-Cl-2-pyridyl CH2CF3i-Pr 3-ClH 3-F-2-pyridyl CF3t-Bu 3-BrH 3-CF3-2-pyridyl CH2CF3Me 3-ClH 3-Me-2-pyridyl CF2CHF2Et 3-ClH 3-Br-2-pyridyl CClF2i-Pr 3-Cl5-Cl3-Br-2-pyridyl CH2CF3t-Bu 3-ClH 3-Br-2-pyridyl CF3i-Pr 3-ClH 3-Br-2-pyridyl CF2CHF2Me 6-ClH Et CHF2Et 6-Br4-MeMe CH2CF3i-Pr 6-ClH Et CH2CF3t-Bu 6-ClCl Me CH2CF3Me 6-ClH Me CH2CF3Et 6-ClH Me CF2CHF2i-Pr 6-F 4-BrMe CHF2t-Bu 6-ClH Me CHF2propargyl 6-ClH Me CBrF2cyclopropyl6-ClH Me CH2Fi-Pr 6-Cl4-ClMe CH2CF3t-Bu 6-ClH Me EtMe 6-ClH Me n-PrEt 6-ClH Et CH2C2F5i-Pr 6-I 4-CNn-Pr CH2CF3t-Bu 6-ClH i-Pr CF3propargyl 6-ClH Cl C2F5cyclopropyl6-ClH F CHF2i-Pr 6-ClH Me CH2CF3t-Bu 6-Cl4-BrMe CHF2Me 6-ClH Me CH2CF3Et 6-F H Me CH2CF3i-Pr 6-ClH Me CH2Clt-Bu 6-Cl4-ClMe CClF2Me 6-ClH Me CH2CH2Cl
R3R4aR4bRvaRvbEt 6-I H Me n-C3F7i-Pr 6-ClH Me i-C3F7t-Bu 6-Cl4-F Me Allylpropargyl 6-ClH CF3CF2CHF2Et 6-ClH CF3i-C3F7i-Pr 6-ClH OMe CF2CHF2t-Bu 6-Cl4-ClHCF2CHF2Me 6-ClH HCF2CHF2Et 6-ClH HMei-Pr 6-ClH HCH2CF3t-Bu 6-BrH HCH2CF3cyclopropyl6-Cl4-BrHCH2CF3Et 6-ClH HC2F5i-Pr 6-ClH HC2F5t-Bu 6-F 4-MeHC2F5Me 6-ClH HCF2CHF2Et 6-ClH HCH2CF3i-Pr 6-CN4-ClHn-C3F3t-Bu 6-ClH Ph i-C3F7propargyl 6-ClH Ph CH2CF3Et 6-ClH Ph CF2CHF2i-Pr 6-ClH 2-pyridylCHF2t-Bu 6-Cl4-Br2-pyridylCH2CF3cyclopropyl6-ClH 2-ClPh CF2CHF2Et 6-F H 2-ClPh CH2CF3i-Pr 6-ClH 2-ClPh CF2CHF2t-Bu 6-ClH 2-ClPh CHF2Me 6-ClH 2-ClPh EtEt 6-Br4-Cl2-BrPh CBrF2i-Pr 6-ClH 2-MePh CH2CF3t-Bu 6-ClH 2-CNPh CF2CHF2Me 6-ClH 2-FPhCH2CF3propargyl 6-ClH 2，6-F2Ph CH2CF3i-Pr 6-BrH 2，4-F2Ph CF2CHF2t-Bu 6-Cl4-CN2，5-F2Ph CH2CF3Me 6-ClH 2-MeOPh CH2CF3
R3R4aR4bRvaRvbEt 6-ClH 3-Cl-2-pyridyl CF2CHF2i-Pr 6-Cl4-Br3-Cl-2-pyridyl CH2CF3t-Bu 6-CNH 3-Cl-2-pyridyl CF2CHF2Me 6-Cl4-I 3-Cl-2-pyridyl CF3Et 6-ClH 3-Cl-2-pyridyl CHF2i-Pr 6-BrH 3-F-2-pyridyl CBrF2t-Bu 6-ClH 3-CF3-2-pyridyl CH2CF3propargyl 6-ClH 3-Me-2-pyridyl CF2CHF2Et 6-Cl4-Br3-Br-2-pyridyl CH2CF3i-Pr 6-ClH 3-Br-2-pyridyl CF3t-Bu 6-ClH 3-Br-2-pyridyl CH2CF3Me 6-ClH 3-Br-2-pyridyl CF2CHF2Table 20 R3R4aR4bRvaRvbMe 3-MeH H CHF2Et 3-Me5-MeH CH2CF3i-Pr 3-MeH H CH2CF3t-Bu 3-Me5-ClMe CH2CF3Me 3-MeH Et CH2CF3Et 3-MeH Me CF2CHF2i-Pr 3-Me5-BrEt CHF2t-Bu 3-MeH Me CHF2propargyl 3-MeH Me CBrF2cyclopropyl3-MeH Me CH2Fi-Pr 3-Me5-ClMe CH2CF3t-Bu 3-MeH Me Et
R3R4aR4bRvaRvbMe 3-Me5-CNMe n-PrEt 3-MeH Me CH2C2F5i-Pr 3-MeH Me CH2CF3t-Bu 3-MeH Me CF3propargyl 3-MeH Me C2F5cyclopropyl3-MeH Et CHF2i-Pr 3-MeH n-Pr CH2CF3t-Bu 3-Me5-Bri-Pr CHF2Me 3-MeH Cl CH2CF3Et 3-MeH FCH2CF3i-Pr 3-MeH Me CH2Clt-Bu 3-Me5-ClMe CClF2Me 3-MeH Me CH2CH2ClEt 3-MeH Me n-C3F7i-Pr 3-MeH Me i-C3F7t-Bu 3-Me5-F Me Allylpropargyl 3-MeH Et CF2CHF2Et 3-MeH Et i-C3F7i-Pr 3-MeH n-Pr CF2CHF2t-Bu 3-Me5-Cli-Pr CF2CHF2Me 3-MeH CF3CF2CHF2Et 3-MeH CF3Mei-Pr 3-MeH OMe CH2CF3t-Bu 3-MeH HCH2CF3cyclopropyl3-Me5-BrHCH2CF3Et 3-MeH HC2F5i-Pr 3-Me5-MeHC2F5t-Bu 3-MeH HC2F5Me 3-MeH HCF2CHF2Et 3-MeH i-Pr CH2CF3i-Pr 3-Me5-ClHn-C3F7t-Bu 3-MeH Hi-C3F7propargyl 3-MeH Ph CH2CF3Et 3-MeH Ph CF2CHF2i-Pr 3-MeH Ph CHF2t-Bu 3-Me5-Br2-pyridylCH2CF3
R3R4aR4bRvaRvbcyclopropyl3-MeH 2-pyridyl CF2CHF2Et 3-MeH 2-ClPh CH2CF3i-Pr 3-MeH 2-ClPh CF2CHF2t-Bu 3-MeH 2-ClPh CHF2Me 3-MeH 2-ClPh EtEt 3-Me5-Cl2-ClPh CBrF2i-Pr 3-MeH 2-BrPh CH2CF3t-Bu 3-MeH 2-MePh CF2CHF2Me 3-MeH 2-CNPh CH2CF3propargyl 3-MeH 2-FPh CH2CF3i-Pr 3-Me5-CN2，6-F2Ph CF2CHF2t-Bu 3-MeH 2，4-F2Ph CH2CF3Me 3-MeH 2，5-F2Ph CH2CF3Et 3-MeH 2-MeOPhCF2CHF2i-Pr 3-Me5-Br3-Cl-2-pyridyl CH2CF3t-Bu 3-MeH 3-Cl-2-pyridyl CF2CHF2Me 3-Me5-I 3-Cl-2-pyridyl CF3Et 3-MeH 3-Cl-2-pyridyl CHF2i-Pr 3-Me5-Me3-Cl-2-pyridyl CBrF2t-Bu 3-MeH 3-F-2-pyridyl CH2CF3propargyl 3-MeH 3-CF3-2-pyridyl CF2CHF2Et 3-Me5-Br3-Me-2-pyridyl CH2CF3i-Pr 3-MeH 3-Br-2-pyridyl CF3t-Bu 3-MeH 3-Br-2-pyridyl CH2CF3Me 3-MeH 3-Br-2-pyridyl CF2CHF2Et 3-MeH 3-Br-2-pyridyl CClF2Me 6-MeH H CHF2Et 6-Me4-MeH CH2CF3i-Pr 6-MeH H CH2CF3t-Bu 6-MeCl Me CH2CF3Me 6-MeH Et CH2CF3Et 6-MeH Me CF2CHF2i-Pr 6-Me4-BrEt CHF2t-Bu 6-MeH Me CHF2propargyl 6-MeH Me CBrF2cyclopropyl6-MeH Me CH2F
R3R4aR4bRvaRvbi-Pr 6-Me4-ClMe CH2CF3t-Bu 6-MeH Me EtMe 6-MeH Me n-PrEt 6-MeH Me CH2C2F5i-Pr 6-Me4-CNMe CH2CF3t-Bu 6-MeH Me CF3propargyl 6-MeH Me C2F5cyclopropyl6-MeH Et CHF2i-Pr 6-MeH n-PrCH2CF3t-Bu 6-Me4-Bri-PrCHF2Me 6-MeH Cl CH2CF3Et 6-MeH F CH2CF3i-Pr 6-MeH Me CH2Clt-Bu 6-Me4-ClMe CClF2Me 6-MeH Me CH2CH2ClEt 6-MeH Me n-C3F7i-Pr 6-MeH Me i-C3F7t-Bu 6-Me4-F Me Allylpropargyl 6-MeH Me CF2CHF2Et 6-MeH Me i-C3F7i-Pr 6-MeH Me CF2CHF2t-Bu 6-Me4-ClMe CF2CHF2Me 6-MeH CF3CF2CHF2Et 6-MeH CF3Mei-Pr 6-MeH OMe CH2CF3t-Bu 6-MeH H CH2CF3cyclopropyl6-Me4-BrH CH2CF3Et 6-MeH H C2F5i-Pr 6-MeH H C2F5t-Bu 6-Me4-MeH C2F5Me 6-MeH H CF2CHF2Et 6-MeH H CH2CF3i-Pr 6-Me4-ClH n-C3F7t-Bu 6-MeH H i-C3F7propargyl 6-MeH H CH2CF3Et 6-MeH H CF2CHF2
R3R4aR4bRvaRvbi-Pr 6-MeH H CHF2t-Bu 6-Me4-BrPh CH2CF3cyclopropyl6-MeH Ph CF2CHF2Et 6-MeH Ph CH2CF3i-Pr 6-MeH 2-pyridyl CF2CHF2t-Bu 6-MeH 2-pyridyl CHF2Me 6-MeH 2-ClPh EtEt 6-Me4-Cl2-ClPh CBrF2i-Pr 6-MeH 2-ClPh CH2CF3t-Bu 6-Me4-CN2-ClPh CF2CHF2Me 6-MeH 2-ClPh CH2CF3propargyl 6-MeH 2-BrPh CH2CF3i-Pr 6-MeH 2-MePh CF2CHF2t-Bu 6-MeH 2-CNPh CH2CF3Me 6-MeH 2-FPh CH2CF3Et 6-MeH 2，6-F2Ph CF2CHF2i-Pr 6-Me4-Br2，4-F2Ph CH2CF3t-Bu 6-MeH 2，5-F2Ph CF2CHF2Me 6-Me4-I 2-MeOPhCF3Et 6-MeH 3-Cl-2-pyridyl CHF2i-Pr 6-MeH 3-Cl-2-pyridyl CBrF2t-Bu 6-MeH 3-Cl-2-pyridyl CH2CF3propargyl 6-MeH 3-Cl-2-pyridyl CF2CHF2Et 6-Me4-Br3-Cl-2-pyridyl CH2CF3i-Pr 6-MeH 3-F-2-pyridyl CF3t-Bu 6-MeH 3-CF3-2-pyridyl CH2CF3Me 6-MeH 3-Me-2-pyridyl CF2CHF2E，6-MeH 3-Br-2-pyridyl CClF2i-Pr 6-Me4-Cl3-Br-2-pyridyl CH2CF3t-Bu 6-MeH 3-Br-2-pyridyl CF3i-Pr 6-MeH 3-Br-2-pyridyl CF2CHF2Me 3-ClH H CHF2Et 3-Br5-MeH CH2CF3i-Pr 3-ClH H CH2CF3t-Bu 3-Cl5-ClMe CH2CF3Me 3-ClH Et CH2CF3
R3R4aR4bRvaRvbEt 3-ClH Me CF2CHF2i-Pr 3-Cl5-BrEt CHF2t-Bu 3-ClH Me CHF2propargyl 3-ClH Me CBrF2cyclopropyl3-ClH Me CH2Fi-Pr 3-Cl5-ClMe CH2CF3t-Bu 3-ClH Me EtMe 3-F H Me n-PrEt 3-ClH Me CH2C2F5i-Pr 3-Cl5-CNMe CH2CF3t-Bu 3-ClH Me CF3propargyl 3-ClH Me C2F5cyclopropyl3-ClH Et CHF2i-Pr 3-ClH n-Pr CH2CF3t-Bu 3-Cl5-Bri-Pr CHF2Me 3-ClH Cl CH2CF3Et 3-BrH F CH2CF3i-Pr 3-ClH Me CH2Clt-Bu 3-Cl5-ClMe CClF2Me 3-ClH Me CH2CH2ClEt 3-ClH Me n-C3F7i-Pr 3-ClH Me i-C3F7t-Bu 3-Cl5-F Me Allylpropargyl 3-ClH Me CF2CHF2Et 3-ClH Me i-C3F7i-Pr 3-BrH Me CF2CHF2t-Bu 3-Cl5-ClMe CF2CHF2Me 3-ClH CF3CF2CHF2Et 3-CNH CF3Mei-Pr 3-ClH OMeCH2CF3t-Bu 3-ClH H CH2CF3cyclopropyl3-Cl5-BrH CH2CF3Et 3-ClH H C2F5i-Pr 3-ClH H C2F5t-Bu 3-ClH H C2F5Me 3-F H H CF2CHF2
R3R4aR4bRvaRvbEt 3-ClH H CH2CF3i-Pr 3-Cl5-ClH n-C3F7t-Bu 3-ClH H i-C3F7propargyl 3-ClH H CH2CF3Et 3-ClH H CF2CHF2i-Pr 3-ClH H CHF2t-Bu 3-Cl5-BrPh CH2CF3cyclopropyl3-ClH Ph CF2CHF2Et 3-ClH Ph CH2CF3i-Pr 3-BrH 2-pyridyl CF2CHF2t-Bu 3-ClH 2-pyridyl CHF2Me 3-ClH 2-ClPh EtEt 3-Cl5-Cl2-ClPh CBrF2i-Pr 3-ClH 2-ClPh CH2CF3t-Bu 3-I H 2-ClPh CF2CHF2Me 3-Cl5-Me2-ClPh CH2CF3propargyl 3-ClH 2-BrPh CH2CF3i-Pr 3-ClH 2-MePh CF2CHF2t-Bu 3-Cl5-CN2-CNPh CH2CF3Me 3-ClH 2-FPh CH2CF3Et 3-ClH 2，6-F2Ph CF2CHF2i-Pr 3-Cl5-Br2，4-F2Ph CH2CF3t-Bu 3-F H 2，5-F2Ph CF2CHF2Me 3-Cl5-I 2-MeOPhCF3Et 3-ClH 3-Cl-2-pyridyl CHF2i-Pr 3-CNH 3-Cl-2-pyridyl CBrF2t-Bu 3-ClH 3-Cl-2-pyridyl CH2CF3propargyl 3-ClH 3-Cl-2-pyridyl CF2CHF2Et 3-Cl5-Br3-Cl-2-pyridyl CH2CF3i-Pr 3-ClH 3-F-2-pyridyl CF3t-Bu 3-BrH 3-CF3-2-pyridyl CH2CF3Me 3-ClH 3-Me-2-pyridyl CF2CHF2Et 3-ClH 3-Br-2-pyridyl CClF2i-Pr 3-Cl5-Cl3-Br-2-pyridyl CH2CF3t-Bu 3-ClH 3-Br-2-pyridyl CF3i-Pr 3-ClH 3-Br-2-pyridyl CF2CHF2
R3R4aR4bRvaRvbMe 6-ClH Et CHF2Et 6-Br4-MeMe CH2CF3i-Pr 6-ClH Et CH2CF3t-Bu 6-ClCl Me CH2CF3Me 6-ClH Me CH2CF3Et 6-ClH Me CF2CHF2i-Pr 6-F 4-BrMe CHF2t-Bu 6-ClH Me CHF2propargyl 6-ClH Me CBrF2cyclopropyl6-ClH Me CH2Fi-Pr 6-Cl4-ClMe CH2CF3t-Bu 6-ClH Me EtMe 6-ClH Me n-PrEt 6-ClH Et CH2C2F5i-Pr 6-I 4-CNn-PrCH2CF3t-Bu 6-ClH i-PrCF3propargyl 6-ClH Cl C2F5cyclopropyl6-ClH F CHF2i-Pr 6-ClH Me CH2CF3t-Bu 6-Cl4-BrMe CHF2Me 6-ClH Me CH2CF3Et 6-F H Me CH2CF3i-Pr 6-ClH Me CH2Clt-Bu 6-Cl4-ClMe CClF2Me 6-ClH Me CH2CH2ClEt 6-I H Me n-C3F7i-Pr 6-ClH Me i-C3F7t-Bu， 6-Cl4-F Me Allylpropargyl 6-ClH CF3CF2CHF2Et 6-ClH CF3i-C3F7i-Pr 6-ClH OMe CF2CHF2t-Bu 6-Cl4-ClH CF2CHF2Me 6-ClH H CF2CHF2Et 6-ClH H Mei-Pr 6-ClH H CH2CF3t-Bu 6-BrH H CH2CF3
R3R4aR4bRvaRvbcyclopropyl6-Cl4-BrH CH2CF3Et 6-ClH H C2F5i-Pr 6-ClH H C2F5t-Bu 6-F 4-MeH C2F5Me 6-ClH H CF2CHF3Et 6-ClH H CH2CF3i-Pr 6-CN4-ClH n-C3F7t-Bu 6-ClH Ph i-C3F7propargyl 6-ClH Ph CH2CF3Et 6-ClH Ph CF2CHF2i-Pr 6-ClH 2-pyridyl CHF2t-Bu 6-Cl4-Br2-pyridyl CH2CF3cyclopropyl6-ClH 2-ClPh CF2CHF2Et 6-F H 2-ClPh CH2CF3i-Pr 6-ClH 2-ClPh CF2CHF2t-Bu 6-ClH 2-ClPh CHF2Me 6-ClH 2-ClPh EtEt 6-Br4-Cl2-BrPh CBrF2i-Pr 6-ClH 2-MePh CH2CF3t-Bu 6-ClH 2-CNPh CF2CHF2Me 6-ClH 2-FPh CH2CF3propargyl 6-ClH 2，6-F2Ph CH2CF3i-Pr 6-BrH 2，4-F2Ph CF2CHF2t-Bu 6-Cl4-CN2，5-F2Ph CH2CF3Me 6-ClH 2-MeOPhCH2CF3Et 6-ClH 3-Cl-2-pyridyl CF2CHF2i-Pr 6-Cl4-Br3-Cl-2-pyridyl CH2CF3t-Bu 6-CNH 3-Cl-2-pyridyl CF2CHF2Me 6-Cl4-I 3-Cl-2-pyridyl CF3Et 6-ClH 3-Cl-2-pyridyl CHF2i-Pr 6-BrH 3-F-2-pyridyl CBrF2t-Bu 6-ClH 3-CF3-2-pyridyl CH2CF3Propargyl 6-ClH 3-Me-2-pyridyl CF2CHF2Et 6-Cl4-Br3-Br-2-pyridyl CH2CF3i-Pr 6-ClH 3-Br-2-pyridyl CF3t-Bu 6-ClH 3-Br-2-pyridyl CH2CF3
R3R4aR4bRvaRvbMe6-ClH 3-Br-2-pyridylCF2HCF2本發(fā)明的生物學(xué)實(shí)施例劑型/應(yīng)用本發(fā)明的化合物一般與農(nóng)業(yè)上適宜的載體一起作為劑型或組合物來(lái)應(yīng)用，適宜的載體包括至少一種液體稀釋劑、固體稀釋劑或表面活性劑。劑型或組合物成分的選擇應(yīng)與有效成分的物理性質(zhì)、應(yīng)用方式和環(huán)境因素例如土壤類(lèi)型、濕度與溫度相一致。有用的劑型包括液體如溶液(包括可乳化的濃縮物)、懸浮劑、乳液(包括微乳劑和/或懸浮劑)等等，它們可任選被粘稠成膠狀物。有用的劑型也包括固體如粉劑、粉末、顆粒劑、片劑、丸劑、薄膜等，它們可以是水分散性的(“可濕的”)或水溶性的。有效成分可被(微)囊化，進(jìn)一步制成懸浮劑或固體劑型；另外也可對(duì)有效成分的整個(gè)劑型進(jìn)行膠囊化(或“外涂敷”)。成膠囊可以控制或延緩有效成分的釋放?？蓢婌F劑型可在適當(dāng)?shù)慕橘|(zhì)中沖稀，使用的噴霧體積為每公頃大約1百至幾百升。高濃度的組合物主要用作進(jìn)一步配制的中間體。
這些劑型一般含有有效量的有效成分、稀釋劑和表面活性劑，其中大約按以下范圍，各組分含量總和為100％(重量計(jì))。

典型的固體稀釋劑在Watkins等人，Handbook of Insecticide DustDiluents and Carriers，2nd Ed.，Dorland Books，Caldwell，NewJersey中作了介紹。典型的液體稀釋劑在Marsden，Solvents Guide，2nd Ed.，Interscience，New York，1950中作了介紹。McCutcheon′s Detergents andEmulsifiers Annual，Allured Publ.Corp.，Ridgewood，New Jersey以及Sisely and Wood，Encyclopedia of Surface Active Agents，Chemical Publ.Co.，Inc.，New York，1964，列出了表面活性劑和推薦應(yīng)用。所有劑型都可含有少量的添加劑，以減少泡沫、結(jié)塊、腐蝕、微生物的生長(zhǎng)等，或加增稠劑以增加粘度。
表面活性劑包括，例如，聚乙氧基化醇、聚乙氧基化烷基酚、聚乙氧基化脫水山梨糖醇脂肪酸酯、磺化丁二酸二烷基酯、硫酸烷基酯、烷基苯磺酸鹽、有機(jī)聚硅氧烷、N，N-二烷基牛磺酸酯、木質(zhì)素磺酸鹽、萘磺酸鹽甲醛縮合物、聚羧酸酯和聚氧乙烯/聚氧丙烯嵌段共聚物。固體稀釋劑包括，例如，粘土如膨潤(rùn)土、蒙脫石、硅鎂土和高嶺土、淀粉、糖、二氧化硅、滑石、硅藻土、尿素、碳酸鈣、碳酸鈉和碳酸氫鈉以及硫酸鈉，液體稀釋劑包括，例如，水、N，N-二甲基甲酰胺、二甲亞砜、N-烷基吡咯烷酮、乙二醇、聚丙二醇、石蠟、烷基苯、烷基萘、橄欖油、蓖麻油、亞麻籽油、桐油、芝麻油、玉米油、花生油、棉籽油、大豆油、菜籽油和椰子油，脂肪酸酯、酮類(lèi)如環(huán)己酮、2-庚酮、異佛爾酮和4-羥基-4-甲基-2-戊酮、和醇類(lèi)如甲醇、環(huán)己醇、十二烷醇和四氫呋喃醇。
溶液，包括可乳化的濃縮物，可以通過(guò)簡(jiǎn)單地混合各組分制得。粉劑和細(xì)粉可通過(guò)混合和通常在捶磨或液能磨中通過(guò)研磨來(lái)制備。懸浮劑一般通過(guò)濕磨來(lái)制備；參見(jiàn)，例如，US 3,060,084。顆粒劑和丸劑通過(guò)將有效物質(zhì)噴到預(yù)先制成的顆粒載體上或通過(guò)造粒技術(shù)來(lái)制備。參見(jiàn)Browning，″Agglomeration″，Chemical Engineering，1967年12月4日，第147-48頁(yè)、Perry′s Chemical Engineer′s Handbook，4th Ed.，McGraw-Hill，New York，1963第8-57頁(yè)和隨后部分，以及PCT公開(kāi)WO 91/13546。丸劑的制備如US 4,172,714中所述。水分散性和水溶性顆粒劑如US 4,144,050、US 3,920,442和DE 3,246,493中教導(dǎo)制備。片劑可如US 5,180,587、US 5,232,701和US 5,208,030中教導(dǎo)制備。薄膜可按照GB 2,095,558和US 3,299,566中教導(dǎo)制備。
有關(guān)劑型技術(shù)的更多信息可參見(jiàn)T.S.Woods，″The Formulator′sToolbox-Product Forms for Modern Agriculture″in Pesticide Chemistryand Bioscience，The Food-Environment Challenge，T.Brooks和T.R.Roberts編輯，Proceedings of the 9th International Congress on PesticideChemistry，The Royal Society of Chemistry，Cambridge，1999第120-133頁(yè)。還參見(jiàn)US 3,235,361第6欄第16行至第7欄第19行和實(shí)施例10-41；US 3,309,192第5欄第43行至第7欄第62行和實(shí)施例8、12、15、39、41、52、53、58、132、138-140、162-164、166、167和169-182；US 2,891,855第3欄第66行至第5欄第17行和實(shí)施例1-4；Klingman，Weed Control as a Science，John Wiley和Sons，Inc.，New York.1961第81-96頁(yè)；和Hance等，Weed Control Handbook，8th Ed.，BlackwellScientific Publications，Oxford，1989。
在以下實(shí)施例中，所有百分?jǐn)?shù)均以重量計(jì)，所有劑型都用常規(guī)方法制備?；衔锾?hào)參見(jiàn)在索引表A中的化合物。
實(shí)施例A可濕性粉劑化合物165.0％十二烷基酚聚乙二醇醚 2.0％木質(zhì)素磺酸鈉 4.0％硅鋁酸鈉 6.0％蒙脫石(煅燒的) 23.0％
實(shí)施例B顆粒劑化合物7 10.0％硅鎂土顆粒(低揮發(fā)物，0.71/0.30mm；U.S.25-50號(hào)篩) 90.0％實(shí)施例C擠壓丸化合物1 25.0％無(wú)水硫酸鈉10.0％粗木質(zhì)素磺酸鈣5.0％烷基萘磺酸鈉 1.0％鈣/鎂膨潤(rùn)土 59.0％實(shí)施例D可乳化的濃縮物化合物7 20.0％油狀可溶性磺酸酯和聚氧乙基醚的混合物 10.0％異佛爾酮 70.0％實(shí)施例E顆粒劑化合物1 0.5％纖維素2.5％乳糖 4.0％玉米粉93.0％本發(fā)明的化合物的特征在于有利的新陳代謝和/或土壤殘留物形式，并顯示對(duì)一定范圍的農(nóng)業(yè)和非農(nóng)業(yè)無(wú)脊椎害蟲(chóng)的防治活性。(在本說(shuō)明書(shū)的上下文中“無(wú)脊椎害蟲(chóng)防治”意思是抑制無(wú)脊椎害蟲(chóng)生長(zhǎng)(包括致死)，從而顯著減少其攝食量或減少害蟲(chóng)引起的其它損失；相關(guān)的表述定義類(lèi)似。)正如本說(shuō)明書(shū)中所述，術(shù)語(yǔ)“無(wú)脊椎害蟲(chóng)”包括具有經(jīng)濟(jì)重要性的節(jié)肢動(dòng)物類(lèi)、腹足動(dòng)物類(lèi)和線蟲(chóng)類(lèi)害蟲(chóng)。術(shù)語(yǔ)“節(jié)肢動(dòng)物”包括昆蟲(chóng)、螨、蜘蛛、蝎子、蜈蚣、千足蟲(chóng)、球潮蟲(chóng)和綜合綱。術(shù)語(yǔ)“腹足動(dòng)物”包括蝸牛、鼻涕蟲(chóng)和其它柄眼目。術(shù)語(yǔ)“線蟲(chóng)”包括所有的寄生蟲(chóng)，例如蛔蟲(chóng)、大惡絲蟲(chóng)和植食性線蟲(chóng)(線蟲(chóng)綱)、吸蟲(chóng)(Tematoda)、棘頭綱和絳蟲(chóng)(多節(jié)絳蟲(chóng)亞綱)。本領(lǐng)域技術(shù)人員將理解，不是所有的化合物對(duì)所有害蟲(chóng)都有相等的藥效。然而，本發(fā)明化合物顯示了對(duì)經(jīng)濟(jì)上具重要性的農(nóng)業(yè)、林業(yè)、溫室、苗圃、觀賞植物、食物和纖維、公共衛(wèi)生和動(dòng)物保健、家庭和商用建筑、家用品、和貯藏產(chǎn)品的害蟲(chóng)的活性。這些包括鱗翅目的幼蟲(chóng)，例如夜蛾科的粘蟲(chóng)、切根蟲(chóng)、尺蠖和heliothines(例如，草地粘蟲(chóng)(Spodoptera fugiperdaJ.E.Smith)、甜菜夜蛾(Spodoptera exigua Hubner)、小地老虎(Agrotisipsilon Hufnagel)、粉紋夜蛾(Trichoplusia ni Hubner)、美洲夜煙蛾(Heliothis virescens Fabricius))；螟蛾科的鉆蛀蟲(chóng)、鞘蛾幼蟲(chóng)、結(jié)網(wǎng)毛蟲(chóng)、錐形蟲(chóng)、卷葉菜蟲(chóng)和雕葉蟲(chóng)(例如，歐洲玉米鉆蛀蟲(chóng)(Ostrinianubilalis Hubner)、臍橙螟(Amyelois transitella Walker)、玉米根結(jié)網(wǎng)毛蟲(chóng)(Crambus caliginosellus Clemens)、草地結(jié)網(wǎng)毛蟲(chóng)(Herpetogrammalicarsisalis Walker))；卷蛾科中的卷葉蛾、蚜蟲(chóng)、種子蠕蟲(chóng)、和水果蠕蟲(chóng)(例如，蘋(píng)果蠹蛾(Cydia pomonella Linnaeus)、葡萄小食心蟲(chóng)(Endopiza viteana Clemens)、梨小食心蟲(chóng)(Grapholita molesta Busck))；和許多其它經(jīng)濟(jì)上重要的鱗翅目(例如，菜蛾(Plutella xylostellaLinnaeus)、紅鈴蟲(chóng)(Pectinophora gossypiella Saunders)、舞毒蛾(Lymantria dispar Linnaeus))；蜚鐮目的蛹和成蟲(chóng)，包括來(lái)自小蠊科和蠊科的(例如，東方蜚鐮(Blatta orientalis Linnaeus)、亞洲蜚鐮(Blatellaasahinai Mizukubo)、德國(guó)蜚鐮(Blattella germanica Linnaeus)、長(zhǎng)須鯡蠊(Supella longipalpa Fabricius)、美洲栗(Periplaneta americanaLinnaeus)、褐色大蠊(Periplaneta brunnea Burmeister)、馬德拉蜚鐮(Leucophaea maderae Fabricius))；鞘翅目的食葉幼蟲(chóng)和成蟲(chóng)，包括來(lái)自長(zhǎng)腳象蟲(chóng)科、豆象科和象蟲(chóng)科的象鼻蟲(chóng)(例如，棉籽象鼻蟲(chóng)(Anthonomus grandis Boheman)、稻象甲(Lissorhoptrus oryzophilusKuschel)、谷象(Sitophilus granarius Linnaeus)、米象(Sitophilus oryzaeLinnaeus))；葉甲科中的跳甲、黃瓜甲蟲(chóng)、根蟲(chóng)、葉蟲(chóng)、薯蟲(chóng)、和潛葉蛾(例如，科羅拉多薯蟲(chóng)(Leptinotarsa decemlineata Say)、玉米根葉甲(Diabrotica virgifera virgifera LeConte))；來(lái)自金龜子科的金龜子和其它甲蟲(chóng)(例如，日本金龜子(Popillia Japonica Newman)和歐洲金龜子(Rhizotrogus majalis Razoumowsky))；來(lái)自皮蠹科的紅緣皮蠹；來(lái)自叩頭蟲(chóng)科的線蟲(chóng)；來(lái)自刺脛小蠹科的樹(shù)皮甲蟲(chóng)和來(lái)自擬步行蟲(chóng)科的粉甲蟲(chóng)。此外農(nóng)業(yè)和非農(nóng)業(yè)害蟲(chóng)包括革翅目的成蟲(chóng)和幼蟲(chóng)，包括來(lái)自球螋科的蠼螋(例如，歐洲球螋(Forficula auricularia Linnaeus)、黑球螋(Chelisoches morio Fabricius))；半翅目和同翅目的成蟲(chóng)和蛹，例如，來(lái)自盲蝽科的盲蝽、來(lái)自蟬科的蟬、來(lái)自大葉蟬科的葉蟬(例如微葉蟬亞種)、來(lái)自樗雞科和飛虱科的樗雞、來(lái)自角蟬科的角蟬、來(lái)自木虱科的木虱、來(lái)自粉虱科的粉虱、來(lái)自蚜科的蚜蟲(chóng)、來(lái)自根瘤蚜科的根瘤蚜、來(lái)自粉蚧科的水蠟蟲(chóng)、來(lái)自蚧科、盾蚧科和珠棉蚧亞科的介殼蟲(chóng)、來(lái)自網(wǎng)蝽科的網(wǎng)蝽、來(lái)自蝽象科的蝽象、來(lái)自長(zhǎng)蝽科的麥長(zhǎng)蝽(例如，長(zhǎng)蝽亞種)和其它實(shí)蝽、來(lái)自沫蟬科的沫蟬、來(lái)自緣蝽科的緣蝽、以及來(lái)自紅蝽科的紅蝽和紅甲蟲(chóng)。還包括螨目的成蟲(chóng)和幼蟲(chóng)，例如葉螨科的蛛螨和紅蜘蛛(例如，歐洲紅蜘蛛(Panonychus ulmi Koch)、兩斑紋蛛螨(Tetranychus urticae Koch)、麥克旦尼氏螨(Tetranychusmcdanieli McGregor))、細(xì)須螨科的flat mites(例如，桔短須螨(Brevipalpus lewisi McGregor))、癭螨科的銹螨和芽螨以及其它食葉螨和在人和動(dòng)物健康中重要的螨，即表皮螨科的塵螨、蠕形螨科的毛囊螨、食甜螨科的干酪螨、蜱目的蜱(例如，鹿蜱(Ixodes scapulars Say)、澳洲癱瘓蜱(Ixodes holocyclus Neumann)、美洲犬蜱(Dermacentorvariabilis Say)、美洲花蜱(Amblyomma americanum Linnaeus)以及癢螨科、蒲螨科和疥螨科的馬癢螨和疥螨；直翅目的成蟲(chóng)和未成年蟲(chóng)，包括螞蚱、蝗蟲(chóng)和蟋蟀(例如，遷徙螞蚱(例如，Melanoplus sanguinipesFabricius、M.differentialis Thomas)、美洲螞蚱(例如，Schistocercaamericana Drury)、沙漠蝗(Schistocerca gregaria Forskal)、飛蝗(Locustamigratoria Linnaeus)、家蟋蟀(Acheta domesticus Linnaeus)、螻蛄(螻蛄屬亞種))；雙翅目的成蟲(chóng)和未成年蟲(chóng)，包括潛葉蛾、蠓、果蠅(實(shí)蠅科)、瑞典桿蠅(例如，Oscinella frit Linnaeus)、土壤蛆、家蠅(例如，Muscadomestica Linnaeus)、小加蠅(例如，F(xiàn)annia canicularis Linnaeus、F.femoralis Stein)、廄螫蠅(例如，Stomoxys calcitrans Linnaeus)、秋家蠅、角蠅、麗蠅(例如，金蠅屬亞種、伏蠅屬亞種)、和其它蠅狀飛蟲(chóng)(muscoidfly pests)、馬蠅(例如，虻屬亞種)、膚蠅(例如，馬胃蠅屬亞種、牛虻屬亞種)、牛皮蠅(例如，下皮屬亞種)、鹿虻(例如，斑虻屬亞種)、羊蜱蠅(例如，Melophagus ovinus Linnaeus)和其它短角亞目、蚊子(例如，伊蚊屬亞種、按蚊屬亞種、庫(kù)蚊屬亞種)、黑蠅(例如，原蚋屬亞種、蚋屬亞種)、蠓、沙蠅、尖眼蕈蚊、和其它長(zhǎng)角亞目；纓翅目的成蟲(chóng)和未成年蟲(chóng)，包括蔥薊馬(Thrips tabaci Lindeman)和其它食葉薊馬；膜翅目的昆蟲(chóng)，包括螞蟻(例如，紅木蟻(Camponotus ferrugineusFabricius)、黑木蟻(Camponotus pennsylvanicus De Geer)、廚蟻(Monomorium pharaonis Linnaeus)、小火蟻(Wasmannia auropunctataRoger)、火蟻(Solenopsis geminata Fabricius)、外引紅火蟻(Solenopsisinvicta Buren)、阿根廷蟻(Iridomyrmex humilis Mayr)、家褐蟻(Paratrechina longicornis Latreille)、鋪道蟻(Tetramorium caespitumLinnaeus)、玉米田蟻(Lasius alienus Forster)、香家蟻(Tapinoma sessileSay))、蜜蜂(包括木蜂)、大黃蜂、胡蜂和黃蜂；等翅目的昆蟲(chóng)，包括東美散白蟻蟻(Reticulitermesflavipes Kollar)、西美散白蟻(Reticulitermeshesperus Banks)、臺(tái)灣乳白蟻(Coptotermes formosanus Shiraki)、移棲楹白蟻(Incisitermes immigrans Snyder)和其它經(jīng)濟(jì)上重要的白蟻；纓尾目的昆蟲(chóng)，例如蠹蟲(chóng)(Lepisma saccharina Linnaeus)和家衣魚(yú)(Thermobia domestica Packard)；食毛目的昆蟲(chóng)并包括頭虱(Pediculushumanus capitis De Geer)、體虱(Pediculus humanus humanusLinnaeus)、雞體虱(Menacanthus stramineus Nitszch)、狗羽虱(Trichodectes canis De Geer)、食毛鳥(niǎo)虱(Goniocotes gallinae De Geer)、羊體虱(Bovicola ovis Schrank)、牛盲虱(Haematopinus eurysternusNitzsch)、犢長(zhǎng)顎虱(Linognathus vituli Linnaeus)和其它攻擊人和動(dòng)物的吸和咬的寄生虱；蚤目的昆蟲(chóng)，包括東方鼠蚤(Xenopsylla cheopisRothschild)、貓?jiān)?Ctenocephalides felis Bouche)、狗蚤(Ctenocephalidescanis Curtis)、雞蚤(Ceratophyllus gallinae Schrank)、禽毒蚤(Echidnophaga gallinacea Westwood)、人蚤(Pulex irritans Linnaeus)和其它折磨動(dòng)物和鳥(niǎo)的蚤。包含的其它節(jié)肢動(dòng)物害蟲(chóng)包括蜘蛛目的蜘蛛，例如褐皮花蛛(Loxosceles reclusa Gertsch & Mulaik)和黑寡婦蜘蛛(Latrodectus mactans Fabricius)，以及蚰蜒形目的蜈蚣，例如家蚰蜒(Scutigera coleoptrata Linnaeus)。本發(fā)明的化合物還對(duì)線蟲(chóng)綱、多節(jié)絳蟲(chóng)亞綱、吸蟲(chóng)綱和棘頭綱的成員有活性，這些成員包括圓線蟲(chóng)目、蛔蟲(chóng)目、蟯蟲(chóng)目、桿狀線蟲(chóng)目、旋尾目和嘴刺目的經(jīng)濟(jì)上重要的成員，例如但不限于經(jīng)濟(jì)上重要的農(nóng)業(yè)害蟲(chóng)(即，根結(jié)線蟲(chóng)屬的根癌線蟲(chóng)、草地墊刀線蟲(chóng)屬的lesion nematodes、根線蟲(chóng)屬的鬃根線蟲(chóng)，等。)以及危害動(dòng)物和人健康的害蟲(chóng)(即，所有經(jīng)濟(jì)上重要的吸蟲(chóng)、絳蟲(chóng)和蛔蟲(chóng)，例如馬內(nèi)的尋常圓線蟲(chóng)、狗內(nèi)的犬弓首蛔蟲(chóng)、羊內(nèi)的捻轉(zhuǎn)血矛線蟲(chóng)、狗內(nèi)的Dirofrlaria immitis Leidy、馬內(nèi)的葉形裸頭絳蟲(chóng)、反芻動(dòng)物內(nèi)的肝片吸蟲(chóng)，等。)。
本發(fā)明的化合物對(duì)以下害蟲(chóng)顯示了特別高的活性鱗翅目(例如，Alabama argillacea Hubner(棉葉波紋夜蛾)、Archips argyrospilaWalker(果樹(shù)卷葉蟲(chóng))、A.rosana Linnaeus(歐洲卷葉蟲(chóng))和其它黃卷蛾屬種、Chilo suppressalis Walker(二化螟)、Cnaphalocrosis medinalisGuenee(稻縱卷葉螟)、Crambus caliginosellus Clemens(玉米根草螟)、Crambus teterrellus Zincken(早熟禾草螟)、Cydia pomonella Linnaeus(蘋(píng)果蠹蛾)、Earias insulana Boisduval(棉斑實(shí)蛾)、Earias vittellaFabricius(棉斑實(shí)蛾)、Helicoverpa armigera Hbner(美洲棉鈴蟲(chóng))、Helicoverpa zea Boddie(玉米穗夜蛾)、Heliothis virescens Fabricius(美洲夜煙蛾)、Herpetogramma licarsisalis Walker(草皮結(jié)網(wǎng)毛蟲(chóng))、Lobesiabotrana Denis & Schiffermuller(葡萄小食心蟲(chóng))、Pectinophoragossypiella Saunders(紅鈴蟲(chóng))、Phyllocnistis citrella Stainton(桔細(xì)潛蛾)、Pieris brassicae Linnaeus(大菜粉蝶)、Pieris rapae Linnaeus(小菜粉蝶)、Plutella xylostella Linnaeus(菜蛾)、Spodoptera exigua Hubner(甜菜夜蛾)、Spodoptera litura Fabricius(斜紋夜蛾、cluster caterpillar)、Spodopteraftugiperda J.E.Smith(草地粘蟲(chóng))、Trichoplusia ni Hubner(粉紋夜蛾)和Tuta absoluta Meyrick(番茄潛葉蛾))。本發(fā)明的化合物還對(duì)來(lái)自同翅目的成員具有商業(yè)上顯著的活性，這些同翅目成員包括Acyrthisiphon pisum Harris(豌豆蚜)、Aphis craccivora Koch(豇豆蚜)、Aphis fabae Scopoli(豆蚜)、Aphis gossypii Glover(棉蚜、甜瓜蚜)、Aphispomi De Geer(蘋(píng)果蚜)、Aphis spiraecola Patch(繡線菊蚜)、Aulacorthumsolani Kaltenbach(毛地黃蚜)、Chaetosiphon fragaefolii Cockerell(草莓蚜)、Diuraphis noxia Kurdjumov/Mordvilko(俄羅斯小麥蚜)、Dysaphisplantaginea Paaserini(蘋(píng)粉紅劣蚜)、Eriosoma lanigerum Hausmann(蘋(píng)綿蚜)、Hyalopteruspruni Geoffroy(梅大尾蚜)、Lipaphis erysimiKaltenbach(蘿卜蚜)、Metopolophium dirrhodum Walker(谷類(lèi)蚜)、Macrosipum euphorbiae Thomas(馬鈴薯蚜)、Myzus persicae Sulzer(桃-薯蚜、桃蚜)、Nasonovia ribisnigri Mosley(萵苣蚜)、天庖瘡亞種(根蚜和纓蚜)、Rhopalosiphum maidis Fitch(玉米葉蚜)、Rhopalosiphum padiLinnaeus(粟縊蚜)、Schizaphis graminum Rondani(麥二叉蚜)、Sitobionavenae Fabricius(英國(guó)谷物蚜)、Therioaphis maculata Buckton(苜蓿斑翅蚜)、Toxoptera aurantii Boyer de Fonscolombe(桔二叉蚜)、和Toxopteracitricida Kirkaldy(桔二岔蚜)；球蚜屬亞種(球蚜)；Phylloxera devastatrixPergande(美核桃根瘤蚜)；Bemisia tabaci Gennadius(菸草粉虱、棉粉虱)、Bemisia argentifolii Bellows & Perring(銀葉粉虱)、Dialeurodes citriAshmead(桔粉虱)和Trialeurodes vaporariorum Westwood(溫室白粉虱)；Empoasca fabae Harris(馬鈴薯微葉蟬)、Laodelphax striatellusFallen(灰飛虱)、Macrolestes quadrilineatus Forbes(紫莞葉蟬)、Nephotettix cinticeps Uhler(大青葉蟬)、Nephotettix nigropictus Stal(黑尾葉蟬)、Nilaparvata lugens Stal(稻褐飛虱)、Peregrinus maidisAshmead(菲島玉米蠟蟬)、Sogatella furcifera Horvath(白背飛虱)、Sogatodes orizicola Muir(美洲稻飛虱)、Typhlocyba pomaria McAtee(蘋(píng)白小葉蟬)、紅斑葉蟬屬亞種(葡萄二星斑葉蟬)；Magicidadaseptendecim Linnaeus(十七年蟑)；Icerya purchasi Maskell(吹棉蚧)、Quadraspidiotus pemiciosus Comstock(梨圓盾蚧)；Planococcus citriRisso(桔粉蚧)；粉蚧屬亞種(其它水蠟蟲(chóng)復(fù)合物)；CacopsyllapyricolaFoerster(木虱)、Trioza diospyri Ashmead(柿木虱)。這些化合物也對(duì)來(lái)自半翅目的成員有活性，這些成員包括Acrosternum hilare Say(喜綠蝽)、Anasa tristis De Geer(南瓜緣蝽)、Blissus leucopterus leucopterusSay(麥長(zhǎng)蝽)、Corythuca gossypii Fabricius(棉網(wǎng)蝽)、Cyrtopeltis modestaDistant(番茄蝽)、Dysdercus suturellus Herrich-Sch ffer(紅甲蟲(chóng))、Euchistus servus Say(褐臭蝽)、Euchistus variolarius Palisot de Beauvois(一點(diǎn)褐蝽)、Graptosthetus亞種(實(shí)蝽的復(fù)合物)、Leptoglossus corculusSay(松籽喙緣蝽)、Lygus lineolaris Palisot de Beauvois(牧草盲蝽)、Nezara viridula Linnaeus(稻綠蝽)、Oebalus pugnax Fabricius(美洲稻盾蝽)、Oncopeltus fasciatus Dallas(大馬利筋長(zhǎng)蝽)、Pseudatomoscelisseriatus Reuter(棉跳盲蝽)。通過(guò)本發(fā)明化合物防治的其它昆蟲(chóng)目包括纓翅目(例如，F(xiàn)rankliniella occidentalis Pergande(苜蓿薊馬)、Scirthothrips citri Moulton(桔實(shí)薊馬)、Sericothrips variabilis Beach(大豆薊馬)、和Thrips tabaci Lindeman(蔥薊馬)；和鞘翅目(例如，Leptinotarsa decemlineata Say(科羅拉多薯蟲(chóng))、Epilachna varivestisMulsant(墨西哥豆瓢蟲(chóng))和叩甲屬(Agriotes)、叩甲屬(Athous)或草金針金屬的金針蟲(chóng))。
本發(fā)明的化合物也可與一種或多種其它生物活性化合物包括殺蟲(chóng)劑、殺真菌劑、殺線蟲(chóng)劑、殺細(xì)菌劑、殺螨劑、生長(zhǎng)調(diào)節(jié)劑如根刺激劑、化學(xué)消毒劑、化學(xué)信息素、驅(qū)避劑、誘引劑、信息激素、攝食刺激劑、其它生物活性化合物或食蟲(chóng)菌、病毒或真菌混合形成多組分農(nóng)藥，給出更廣譜的農(nóng)業(yè)保護(hù)作用。因此本發(fā)明的組合物還可以包括生物有效量的至少一種其它生物活性化合物或試劑?？膳c本發(fā)明化合物一起加工的這些生物活性化合物的實(shí)例是殺蟲(chóng)劑如阿維菌素、乙酰甲胺磷、吡蟲(chóng)清、齊墩螨素、艾扎丁、保棉磷、氟氯菊酯、聯(lián)苯肼酯、噻嗪酮、呋喃丹、氟唑蟲(chóng)清、定蟲(chóng)隆、毒死蜱、甲基毒死蜱、chromafenozide、clothianidin、氟氯氰菊酯、β-氟氯氰菊酯、氯氟氰菊酯、λ-氯氟氰菊酯、氯氰菊酯、滅蠅胺、溴氰菊酯、殺螨硫隆、二嗪農(nóng)、氟脲殺、樂(lè)果、噁茂醚、emamectin、硫丹、高殺滅菊酯、ethiprole、苯硫威、苯氧威、甲氰菊酯、唑螨酯、殺滅菊酯、銳勁特、flonicamid、氟氰戊菊酯、τ-氟胺氰菊酯、氟蟲(chóng)脲、地蟲(chóng)磷、特丁苯酰肼、氟鈴脲、吡蟲(chóng)啉、噁二唑蟲(chóng)、丙胺膦、氟丙氧脲、馬拉硫磷、四聚乙醛、甲胺磷、殺撲磷、滅多蟲(chóng)、烯蟲(chóng)酯、甲氧滴滴涕、久效磷、甲氧苯酰肼、硝蟲(chóng)噻嗪、甲氨叉威、殺線威、對(duì)硫磷、甲基對(duì)硫磷、氯菊酯、甲拌磷、伏殺硫磷、亞胺硫磷、磷胺、抗蚜威、丙溴磷、拒嗪酮、pyridalyl、蚊蠅醚、魚(yú)藤酮、艾克敵105、乙丙硫磷、雙苯酰肼、伏蟲(chóng)隆、七氟菊酯、特丁硫磷、殺蟲(chóng)畏、thiacloprid、thiamethoxam、硫雙威、殺蟲(chóng)雙、四溴菊酯、敵百蟲(chóng)和殺蟲(chóng)??；殺真菌劑如噻二唑素、腈嘧菌酯、苯菌靈、殺稻瘟菌素-S、波爾多液(堿式硫酸銅)、糠菌唑、氯環(huán)丙酰胺、敵菌丹、克菌丹、多菌靈、地茂散、百菌清、氧氯化銅、銅鹽、cyflufenamid、霜脲氰、環(huán)丙唑醇、嘧菌環(huán)胺、(S)-3，5-二氯-N-(3-氯-1-乙基-1-甲基-2-氧丙基)-4-甲基苯甲酰胺(RH 7281)、雙氯氰菌胺(S-2900)、噠菌清、氯硝胺、噁醚唑、(S)-3，5-二氫-5-甲基-2-(甲硫基)-5-苯基-3-(苯氨基)-4H-咪唑-4-酮(RP 407213)、烯酰嗎啉、dimoxystrobin、烯唑醇、烯唑醇-M、多果定、敵瘟磷、氧唑菌、噁唑酮菌、fenamidone、氯苯嘧啶醇、腈苯唑、fencaramid(SZX0722)、拌種咯、苯銹啶、丁苯嗎啉、薯瘟錫、毒菌錫、氟啶胺、咯菌腈、氟聯(lián)苯菌(RPA 403397)、氟喹唑、氟硅唑、氟酰胺、粉唑醇、滅菌丹、三乙膦酸鋁、呋霜靈、呋吡唑靈(S-82658)、己唑醇、種菌唑、異稻瘟凈、異菌脲、稻瘟靈、春雷霉素、亞胺菌、代森錳鋅、代森錳、mefenoxam、滅銹胺、甲霜靈、葉菌唑、叉氨苯酰胺(SSF-126)、腈菌唑、田安(甲胂酸鐵)、惡霜靈、戊菌唑、戊菌隆、烯丙苯噻唑、咪鮮胺、霜霉威、丙環(huán)唑、啶斑肟、pyraclostrobin、二甲嘧菌胺、咯喹酮、喹氧靈、螺噁茂胺、硫磺粉、戊唑醇、四氟醚唑、噻菌靈、噻呋酰胺、甲基硫菌靈、福美雙、tiadinil、三唑酮、三唑醇、三環(huán)唑、肟菌酯、滅菌唑、有效霉素和乙烯菌核利；殺線蟲(chóng)劑如涕滅威、甲氨叉威和克線磷；殺細(xì)菌劑如鏈霉素；殺螨劑如殺螨脒、滅螨猛、乙酯殺螨醇、三環(huán)錫、開(kāi)樂(lè)散、除螨靈、特苯噁唑、喹螨醚、殺螨錫、甲氰菊酯、唑螨酯、噻螨酮、克螨特、噠螨酮和吡螨胺；和生物制劑如蘇云金桿菌，包括鲇澤亞種和庫(kù)爾斯塔克亞種，蘇云金桿菌δ毒素、桿狀病毒以及食蟲(chóng)細(xì)菌、病毒和真菌。
有關(guān)這些農(nóng)業(yè)保護(hù)劑的常規(guī)參考文獻(xiàn)是The Pesticide Manual，第12版，C.D.S.Tomlin出版，British Crop Protection Council，F(xiàn)arnham，Surrey，U.K.，2000。
其中重要的組合物包括(除了式I組份和任意表面活性劑和/或稀釋劑之外)至少一種選自以下的生物活性化合物或試劑阿維菌素、乙酰甲胺磷、吡蟲(chóng)清、amidoflument、齊墩螨素、艾扎丁、保棉磷、氟氯菊酯、聯(lián)苯肼酯、噻嗪酮、呋喃丹、氟唑蟲(chóng)清、定蟲(chóng)隆、毒死蜱、甲基毒死蜱、chromafenozide、clothianidin、氟氯氰菊酯、β-氟氯氰菊酯、氯氟氰菊酯、λ-氯氟氰菊酯、氯氰菊酯、滅蠅胺、溴氰菊酯、殺螨硫隆、二嗪農(nóng)、氟脲殺、樂(lè)果、噁茂醚、emamectin、硫丹、高殺滅菊酯、ethiprole、苯硫威、苯氧威、甲氰菊酯、殺滅菊酯、銳勁特、flonicamid、氟氰戊菊酯、τ-氟胺氰菊酯、氟蟲(chóng)脲、地蟲(chóng)磷、特丁苯酰肼、氟鈴脲、吡蟲(chóng)啉、噁二唑蟲(chóng)、丙胺膦、氟丙氧脲、馬拉硫磷、四聚乙醛、甲胺磷、殺撲磷、滅多蟲(chóng)、烯蟲(chóng)酯、甲氧滴滴涕、久效磷、甲氧苯酰肼、硝蟲(chóng)噻嗪、甲氨叉威、殺線威、對(duì)硫磷、甲基對(duì)硫磷、氯菊酯、甲拌磷、伏殺硫磷、亞胺硫磷、磷胺、抗蚜威、丙溴磷、拒嗪酮、pyridalyl、蚊蠅醚、魚(yú)藤酮、艾克敵105、乙丙硫磷、雙苯酰肼、伏蟲(chóng)隆、七氟菊酯、特丁硫磷、殺蟲(chóng)畏、thiacloprid、thiamethoxam、硫雙威、殺蟲(chóng)雙、四溴菊酯、敵百蟲(chóng)和殺蟲(chóng)隆、涕滅威、甲氨叉威、克線磷、殺螨脒、滅螨猛、乙酯殺螨醇、三環(huán)錫、開(kāi)樂(lè)散、除螨靈、特苯噁唑、喹螨醚、殺螨錫、甲氰菊酯、唑螨酯、噻螨酮、克螨特、噠螨酮、吡螨胺；蘇云金桿菌，包括鲇澤亞種和庫(kù)爾斯塔克亞種，蘇云金桿菌δ毒素、桿狀病毒以及食蟲(chóng)細(xì)菌、病毒和真菌。
用于與本發(fā)明化合物混合的優(yōu)選的殺蟲(chóng)劑和殺螨劑包括擬除蟲(chóng)菊酯類(lèi)，如氯氰菊酯、氯氟氰菊酯、氟氯氰菊酯、β-氟氯氰菊酯，高殺滅菊酯、殺滅菊酯和四溴菊酯；氨基甲酸酯類(lèi)如苯硫威、滅多蟲(chóng)、甲氨叉威和硫雙滅多蟲(chóng)；類(lèi)煙堿類(lèi)如噻蟲(chóng)胺、吡蟲(chóng)啉和噻蟲(chóng)啉；神經(jīng)鈉通道阻斷劑如噁二唑蟲(chóng)、殺蟲(chóng)的大環(huán)內(nèi)酯如艾克敵105、阿維菌素、齊墩螨素和emamectin；-氨基丁酸(GABA)拮抗劑如硫丹、ethiprole和銳勁特；殺蟲(chóng)的脲類(lèi)如氟蟲(chóng)脲和殺蟲(chóng)?。槐Ｓ准に啬M物如噁茂醚和蚊蠅醚；拒嗪酮；和蟲(chóng)螨脒。用于與本發(fā)明化合物混合的優(yōu)選生物制劑包括蘇云金桿菌和蘇云金桿菌δ毒素以及天然存在和遺傳改性的病毒殺蟲(chóng)劑，包括桿狀病毒類(lèi)以及食蟲(chóng)真菌。
最優(yōu)選的混合物包括本發(fā)明化合物與氟氯氰菊酯的混合物；本發(fā)明化合物與β-氯氟氰菊酯的混合物；本發(fā)明的化合物與高殺滅菊酯的混合物；本發(fā)明的化合物與滅多蟲(chóng)的混合物；本發(fā)明化合物與吡蟲(chóng)啉的混合物；本發(fā)明化合物與噻蟲(chóng)啉的混合物；本發(fā)明化合物與噁二唑蟲(chóng)的混合物；本發(fā)明化合物與阿維菌素的混合物；本發(fā)明化合物與硫丹的混合物；本發(fā)明化合物與ethiprole的混合物；本發(fā)明化合物與銳勁特的混合物；本發(fā)明化合物與氟蟲(chóng)脲的混合物；本發(fā)明化合物與蚊蠅醚的混合物；本發(fā)明化合物與拒嗪酮的混合物；本發(fā)明化合物與蟲(chóng)螨脒的混合物；本發(fā)明化合物與蘇云金桿菌的混合物和本發(fā)明化合物與蘇云金桿菌δ毒素的混合物。
在某些情況下，和其它具有類(lèi)似的防治譜，但作用方式不同的無(wú)脊椎害蟲(chóng)防治化合物或試劑混合將特別有利于抗性管理。因此，本發(fā)明的化合物還可以包括生物有效量的至少一種具有類(lèi)似防治譜，但作用方式不同的其它無(wú)脊椎害蟲(chóng)防治化合物或試劑。將生物有效量的本發(fā)明化合物與經(jīng)基因改性以表達(dá)植物保護(hù)化合物(例如蛋白質(zhì))的植物或該植物的部位接觸，也可以提供更廣譜的植物保護(hù)并有利于抗性管理。
在農(nóng)業(yè)和非農(nóng)業(yè)領(lǐng)域，通過(guò)將一種或多種有效量的本發(fā)明化合物施加于無(wú)脊椎害蟲(chóng)的環(huán)境(包括農(nóng)業(yè)和/或非農(nóng)業(yè)的害蟲(chóng)侵染地)、施用于被保護(hù)的區(qū)域，或者直接施用于被防治的害蟲(chóng)上，都可以防治無(wú)脊椎害蟲(chóng)。因此，本發(fā)明進(jìn)一步包括一種防治農(nóng)業(yè)和/或非農(nóng)業(yè)領(lǐng)域中無(wú)脊椎害蟲(chóng)的方法，該方法包括用有效量的一種或多種本發(fā)明的化合物，或者用含有至少一種這種化合物的組合物或含有至少一種這種化合物和有效量的至少一種其它生物活性化合物或試劑的組合物與這些無(wú)脊椎害蟲(chóng)或其環(huán)境接觸。包括本發(fā)明化合物和有效量的至少一種其它生物活性化合物或試劑的適宜組合物的實(shí)例包括顆粒組合物，其中其它生物活性化合物存在于與本發(fā)明化合物相同的顆粒上，或者存在于于本發(fā)明化合物顆粒分開(kāi)的顆粒上。
接觸的優(yōu)選方法是噴霧。此外，含有本發(fā)明化合物的顆粒組合物可施用于植物的葉面或土壤。本發(fā)明的化合物還通過(guò)以液體劑型進(jìn)行土壤浸濕、以顆粒劑型用于土壤、在移植中用于護(hù)理盒處理或浸漬，將植物與含有本發(fā)明化合物的組合物接觸，經(jīng)植物攝取有效地供給。通過(guò)將含有本發(fā)明化合物的組合物局部施用到侵染部位也可以發(fā)揮化合物的效力。其它接觸方法包括通過(guò)直接或滯留噴霧、飛機(jī)噴灑、凝膠、種子包衣、微膠囊化、全身性攝入、餌、耳標(biāo)、丸劑、迷霧器、熏蒸劑、氣霧劑、粉劑和許多其它方式施用本發(fā)明的化合物或組合物。本發(fā)明的化合物也可摻入制備無(wú)脊椎害蟲(chóng)防治設(shè)備(例如昆蟲(chóng)網(wǎng)捕)的材料中。
本發(fā)明化合物可摻入無(wú)脊椎害蟲(chóng)消耗的餌劑中或例如捕獲器等設(shè)備中。含有0.01-5％活性組分，0.05-10％保水劑和40-99％蔬菜粉的顆?；蝠D劑以非常低的施用比率防治土壤昆蟲(chóng)是有效的，特別是對(duì)于通過(guò)消化而不是通過(guò)直接接觸致死的活性組分的劑量。
本發(fā)明的化合物可以它們的純凈狀態(tài)被施用，但最普遍使用的是含有一種或多種化合物與適當(dāng)?shù)妮d體、稀釋劑和表面活性劑的劑型，并可以與食品混合，這取決于預(yù)期的最終用途。優(yōu)選的施用方法包括噴灑化合物的水分散液或精煉油溶液。與噴霧油、噴霧油濃制劑、鋪展增稠劑、助劑、其它溶劑和增效劑如胡椒基丁醚一起，常常可提高化合物的功效。
有效防治所需的施藥量(即“生物有效量”)取決于以下因素被防治的無(wú)脊椎害蟲(chóng)的品系、害蟲(chóng)的生命周期、生命階段、它的大小、地點(diǎn)、一年中的時(shí)期、寄生作物或動(dòng)物、喂飼行為、交配行為、空氣濕度、溫度等。在通常環(huán)境下，每公頃大約0.01-2kg有效成分的施藥量對(duì)農(nóng)業(yè)生態(tài)系中的害蟲(chóng)防治是足夠的，但少至0.0001kg/公頃可能是有效的，或多至8kg/公頃可能是需要的。對(duì)于非農(nóng)業(yè)應(yīng)用，有效使用量范圍是大約1.0-50mg/m2，但少至0.1mg/m2可能是有效的，或多至150mg/m2可能是需要的。本領(lǐng)域技術(shù)人員可以容易地確定對(duì)所需的無(wú)脊椎害蟲(chóng)的防治水平所需的生物有效量。
本發(fā)明生物學(xué)實(shí)施例的以下試驗(yàn)表明了本發(fā)明方法防止特定無(wú)脊椎害蟲(chóng)妨害植物的功效?！胺乐喂πА贝韺?duì)無(wú)脊椎害蟲(chóng)發(fā)育的抑制(包括死亡)，抑制會(huì)引起明顯的攝食減少。由這些化合物產(chǎn)生的害蟲(chóng)防治保護(hù)并不限于這些品系。關(guān)于化合物的說(shuō)明見(jiàn)索引表A。在該索引表中采用的縮寫(xiě)如下t是叔，n是正，i是異，s是仲，c是環(huán)，Me是甲基，Et是乙基，Pr是丙基，Bu是丁基；因此i-Pr是異丙基，s-Bu是仲丁基等?？s寫(xiě)“Ex.”代表“實(shí)施例”，其后跟著的數(shù)字表示化合物在該實(shí)施例中被制備。
索引表A 化合物R3R4R5熔點(diǎn)℃1 t-BuH2，3-diMe 208-2092 i-PrH4-OCF3160-1613(Ex.4)i-Pr5-Cl 4-OCF3230-2334 Me 5-Me 4-OCF3224-2255 Me 5-Me 2-Me，4-Cl 114-1166 i-Pr5-Cl 2-Me，4-Cl ＞2507(Ex.3)i-Pr2-Me 2-Me，4-OCF32308 t-Bu2-Me 2-Me，4-OCF3200-2039(Ex.2)i-Pr2-Me 2-Me，4-CF323010 i-Pr5-NO24-CF3Solid11 4-CF3-Ph 5-Me 2-Me＞250
索引表B 化合物R3R4J熔點(diǎn)℃12t-BuH 2，3-diMe-Ph 161-16413t-BuH 2-CF3-Ph 173-17414i-PrH 2，4-F-Ph 14815i-PrH 2，3-diMe-Ph 169-17116t-BuH 2，4-diF-Ph 146-14917i-Pr5-Me2，3-diMe-Ph 202-20518i-Pr5-Me2，6-diCl-Ph 23019i-Pr5-Me2，4-diF-Ph 19620Me H 2-F-Ph固體21i-Pr5-Cl2-Me，4-Cl，6-NC(O)CF320322i-Pr5-Cl2-Me，4-Cl，6-NC(O)CH3＞25023t-Bu5-Me3-CF3-Ph 固體24t-Bu5-Me2-F，5-CF3-Ph固體25t-Bu5-Me4-CF3-Ph 固體26t-Bu5-Me4-OCF3-Ph固體27i-Pr5-Me4-CF3-Ph 固體28i-Pr5-Me3-CF3-Ph 固體29t-Bu5-Me4-CF3-Ph 固體30t-Bu5-Me4-OCF3-Ph固體31i-Pr5-Me2-F，5-CF3-Ph固體32i-Pr5-Me4-OCF3-Ph固體33i-Pr5-Me4-CF3-Ph 固體34t-Bu5-Me3-CF3-Ph 固體索引表C 化合物R3R4R5aR5b熔點(diǎn)℃35(Ex.1)i-Pr 5-Me2-Cl-Ph CF3Solid36 Me5-Me3-Cl-2-PyridylCF3204-20537(Ex.6)i-Pr 5-Me3-Cl-2-PyridylCF3219-22038 NHEt 5-Me3-Cl-2-PyridylCF3185-18639 NHi-Pr5-Me3-Cl-2-PyridylCF3191-19240 t-Bu 5-Me3-Cl-2-PyridylCF3205-20641 Me5-Me3-Cl-2-PyridylCl 201-20242 i-Pr 5-Me3-Cl-2-PyridylCl 229-23043 NHEt 5-Me3-Cl-2-PyridylCl 187-18844 NHi-Pr5-Me3-Cl-2-PyridylCl 195-19645 t-Bu 5-Me3-Cl-2-PyridylCl 201-20246 Me5-Me3-Cl-2-PyridylBr 176-17747 i-Pr 5-Me3-Cl-2-PyridylBr 237-23848 NHEt 5-Me3-Cl-2-PyridylBr 176-17749 NHi-Pr5-Me3-Cl-2-PyridylBr 192-19350 t-Bu 5-Me3-Cl-2-PyridylBr 196-19751 i-Pr 2-Me3-Cl-2-PyridylBr 190-19152 i-Pr 2-Me3-Cl-2-PyridylCl 185-18653(Ex.5)i-Pr 2-Me3-Cl-2-PyridylCF3215-21754 Me2-Me3-Cl-2-PyridylCF3167-168其中，pyridyl為吡啶基索引表D 化合物R3R4R5aR5b熔點(diǎn)℃55 Me 5-Me2-Cl-Ph CF3194-19556 i-Pr5-Me2-Cl-Ph CF3244-24657 t-Bu5-Me2-Cl-Ph CF326058 Et 5-Me2-Cl-Ph CF3236-23759 i-Pr2-Me2-Cl-Ph CF3203-20560 t-Bu2-Me2-Cl-Ph CF3232-23361 Et 2-Me2-Cl-Ph CF3170-17262 Me 2-Me2-Cl-Ph CF3212-21363 Me 5-Me3-Cl-2-PyridylCF3192-19364 Me 2-Me3-Cl-2-PyridylCF323665(Ex.7)i-Pr2-Me3-Cl-2-PyridylCF3198其中，pyridyl為吡啶基本發(fā)明的生物實(shí)施例試驗(yàn)為了評(píng)價(jià)對(duì)菜蛾(Plutella xylostella)的防治，試驗(yàn)單元由小開(kāi)口容器組成，其中裝有12-14-天大的蘿卜植物。預(yù)先對(duì)該單元進(jìn)行侵染用核芯取樣器從生長(zhǎng)有許多幼蟲(chóng)的硬化害蟲(chóng)飼料薄片上取下一芯桿，其上的害蟲(chóng)飼料帶有10-15只嬰幼蟲(chóng)，將帶有幼蟲(chóng)和飼料的芯桿轉(zhuǎn)移到試驗(yàn)單元。隨著飼料芯桿的干透，幼蟲(chóng)轉(zhuǎn)移到試驗(yàn)植物上。
除非另有說(shuō)明，試驗(yàn)化合物被配制成一溶液，其中含有10％丙酮、90％水和300ppm含有烷基芳基聚氧乙烯、游離脂肪酸、二醇和異丙醇的X-77_ Spreader Lo-Foam Formula非離子表面活性劑(LovelandIndustries，Inc.)。將經(jīng)配制的化合物以1mL液體的形式，通過(guò)SUJ2霧化噴嘴噴出，其中1/8JJ通體(Spraying Systems Co.)被固定在每個(gè)試驗(yàn)單元的頂部上方1.27cm(0.5英寸)處。本篩選中的所有試驗(yàn)化合物都以50ppm噴霧，重復(fù)3次。將配制的試驗(yàn)化合物噴灑之后，將每個(gè)試驗(yàn)單元干燥1小時(shí)，然后將一個(gè)黑色篩帽放于上面。這些試驗(yàn)單元在25℃和70％相對(duì)濕度的生長(zhǎng)室內(nèi)保持6天。然后目測(cè)植物受到的侵食危害。
以下試驗(yàn)的化合物提供了優(yōu)異的植物保護(hù)水平(30％或更低的侵食危害)11，37，39，43，47，48，51，52，53和63。
權(quán)利要求
1.一種防治無(wú)脊椎害蟲(chóng)的方法，包括用生物有效量的式I的化合物，包括其所有幾何異構(gòu)體和立體異構(gòu)體、其N(xiāo)-氧化物或其適用于農(nóng)業(yè)的鹽，來(lái)接觸所述無(wú)脊椎害蟲(chóng)或其環(huán)境 其中J是苯環(huán)、萘環(huán)系、5-或6-元雜芳環(huán)或者芳族8-、9-或10-元稠合雜二環(huán)環(huán)系，其中每一環(huán)或環(huán)系任選取代有1-4個(gè)R5；K是-C(＝A)NR2-或-NR2C(＝A)-；L是-NR1C(＝B)-R3或-NR1SO2-R3；A和B獨(dú)立地是O或S；R1是H；或C1-C6烷基、C2-C6鏈烯基、C2-C6鏈炔基或C3-C6環(huán)烷基，每一個(gè)任選取代有一個(gè)或多個(gè)選自如下的取代基鹵素、CN、NO2、羥基、C1-C4烷氧基、C1-C4烷硫基、C1-C4烷基亞磺酰基、C1-C4烷基磺?；?、C2-C4烷氧基羰基、C1-C4烷基氨基、C2-C8二烷基氨基和C3-C6環(huán)烷基氨基；或者R1是C2-C6烷基羰基、C2-C6烷氧基羰基、C2-C6烷基氨基羰基或C3-C8二烷基氨基羰基；R2是H、C1-C6烷基、C2-C6鏈烯基、C2-C6鏈炔基、C3-C6環(huán)烷基、C1-C4烷氧基、C1-C4烷基氨基、C2-C8二烷基氨基、C3-C6環(huán)烷基氨基、C2-C6烷氧基羰基或C2-C6烷基羰基；R3是C1-C6烷基、C2-C6鏈烯基、C2-C6鏈炔基或C3-C6環(huán)烷基，每一個(gè)任選取代有一個(gè)或多個(gè)選自如下的取代基鹵素、CN、NO2、羥基、C1-C4烷氧基、C1-C4鹵烷氧基、C1-C4烷硫基、C1-C4烷基亞磺?；?、C1-C4烷基磺?；2-C6烷氧基羰基、C2-C6烷基羰基、C3-C6三烷基甲硅烷基、苯基、苯氧基和5-或6-元雜芳環(huán)，每個(gè)苯基、苯氧基和5-或6-元雜芳環(huán)任選取代有1-3個(gè)獨(dú)立地選自如下的取代基R6；C1-C4烷氧基；C1-C4烷基氨基；C2-C8二烷基氨基；C1-C4烷氧基(C1-C4烷基)氨基；C3-C6環(huán)烷基氨基；C2-C6烷氧基羰基或C2-C6烷基羰基；或者R1和R3可以與-NC(＝B)-或-NSO2-部分在一起，它們相連形成一個(gè)包括2-6個(gè)碳原子并任選還包括一個(gè)氮、硫或氧原子的環(huán)，所述環(huán)任選取代有1-4個(gè)選自如下的取代基C1-C2烷基、鹵素、CN、NO2和C1-C2烷氧基；每個(gè)R4獨(dú)立地是H、C1-C6烷基、C2-C6鏈烯基、C2-C6鏈炔基、C3-C6環(huán)烷基、C1-C6鹵烷基、C2-C6鹵鏈烯基、C2-C6鹵鏈炔基、C3-C6鹵環(huán)烷基、鹵素、CN、NO2、羥基、C1-C4烷氧基、C1-C4鹵烷氧基、C1-C4烷硫基、C1-C4烷基亞磺?；1-C4烷基磺?；?、C1-C4鹵烷硫基、C1-C4鹵烷基亞磺酰基、C1-C4鹵烷基磺?；?、C1-C4烷基氨基、C2-C8二烷基氨基、C3-C6環(huán)烷基氨基、C3-C6三烷基甲硅烷基，或者任選取代有1-3個(gè)獨(dú)立地選自R6的取代基的苯環(huán)；每個(gè)R5獨(dú)立地是C1-C6烷基、C2-C6鏈烯基、C2-C6鏈炔基、C3-C6環(huán)烷基、C1-C6鹵烷基、C2-C6鹵鏈烯基、C2-C6鹵鏈炔基、C3-C6鹵環(huán)烷基、鹵素、CN、CO2H、CONH2、NO2、羥基、C1-C4烷氧基、C1-C4鹵烷氧基、C1-C4烷硫基、C1-C4烷基亞磺?；?、C1-C4烷基磺?；?、C1-C4鹵烷硫基、C1-C4鹵烷基亞磺?；1-C4鹵烷基磺?；1-C4烷基氨基、C2-C8二烷基氨基、C3-C6環(huán)烷基氨基、C2-C6烷基羰基、C2-C6烷氧基羰基、C2-C6烷基氨基羰基、C3-C8二烷基氨基羰基、C3-C6三烷基甲硅烷基；或者每個(gè)R5獨(dú)立地是苯基、芐基、苯甲?；?、苯氧基、5-或6-元雜芳環(huán)或者芳族8-、9-或10-元稠合雜二環(huán)環(huán)系，每個(gè)苯基、芐基、苯甲?；?、苯氧基、雜芳環(huán)和芳族稠合雜二環(huán)環(huán)系任選取代有1-3個(gè)獨(dú)立地選自R6的取代基；或者兩個(gè)R5基團(tuán)與相鄰碳原子相連時(shí)可以在一起為-OCF2O-、-CF2CF2O-或-OCF2CF2O-；每個(gè)R6獨(dú)立地是C1-C4烷基、C2-C4鏈烯基、C2-C4鏈炔基、C3-C6環(huán)烷基、C1-C4鹵烷基、C2-C4鹵鏈烯基、C2-C4鹵鏈炔基、C3-C6鹵環(huán)烷基、鹵素、CN、NO2、C1-C4烷氧基、C1-C4鹵烷氧基、C1-C4烷硫基、C1-C4烷基亞磺?；1-C4烷基磺?；1-C4烷基氨基、C2-C8二烷基氨基、C3-C6環(huán)烷基氨基、C3-C6(烷基)環(huán)烷基氨基、C2-C4烷基羰基、C2-C6烷氧基羰基、C2-C6烷基氨基羰基、C3-C8二烷基氨基羰基或C3-C6三烷基甲硅烷基；和n是1、2、3或4；條件是L不是-NHC(＝O)-，并且R3不是取代有一個(gè)或多個(gè)氟部分的C1-C6烷基。
2.如權(quán)利要求1的方法，其中K是-C(＝A)NR2-，并且A和B都是O。
3.如權(quán)利要求1的方法，其中K是-NR2C(＝A)-，并且A和B都是O。
4.如權(quán)利要求2或權(quán)利要求3的方法，其中J是苯環(huán)或者5-或6-元雜芳環(huán)，該雜芳環(huán)選自基團(tuán)J-1、J-2、J-3和J-4，每個(gè)J環(huán)任選取代有1-3個(gè)R5 Q是O、S或NR5c；W、X、Y和Z獨(dú)立地是N或CR5c，條件是在J-3和J-4中W、X、Y或Z中至少一個(gè)是N；R1和R2各自獨(dú)立地是H、C1-C4烷基、C2-C4鏈烯基、C2-C4鏈炔基、C3-C6環(huán)烷基、C2-C6烷基羰基或C2-C6烷氧基羰基；R3是C1-C6烷基、C2-C6鏈烯基、C2-C6鏈炔基或C3-C6環(huán)烷基，它們各自任選取代有一個(gè)或多個(gè)選自如下的取代基鹵素、CN、C1-C2烷氧基、C1-C2烷硫基、C1-C2烷基亞磺酰基和C1-C2烷基磺?；?；每個(gè)R4獨(dú)立地是C1-C4烷基、C1-C4鹵烷基、鹵素、CN、NO2、C1-C4烷氧基、C1-C4鹵烷氧基、C1-C4烷硫基、C1-C4烷基亞磺酰基、C1-C4烷基磺酰基、C1-C4鹵烷硫基、C1-C4鹵烷基亞磺?；駽1-C4鹵烷基磺酰基；每個(gè)R5獨(dú)立地是C1-C4烷基、C1-C4鹵烷基、鹵素、CN、NO2、C1-C4烷氧基、C1-C4鹵烷氧基、C1-C4烷硫基、C1-C4烷基亞磺?；?、C1-C4烷基磺?；1-C4鹵烷硫基、C1-C4鹵烷基亞磺酰基、C1-C4鹵烷基磺?；2-C4烷氧基羰基或C3-C8二烷基氨基羰基；或每個(gè)R5獨(dú)立地是苯基、芐基或者5-或6-元雜芳環(huán)，每個(gè)環(huán)任選取代有1-3個(gè)獨(dú)立地選自R6的取代基；或者兩個(gè)R5基團(tuán)與相鄰碳原子相連時(shí)可以在一起為-OCF2O-、-CF2CF2O-或-OCF2CF2O-；R5c是H或R5；每個(gè)R6獨(dú)立地是C1-C4烷基、C2-C4鏈烯基、C2-C4鏈炔基、C3-C6環(huán)烷基、C1-C4鹵烷基、C2-C4鹵鏈烯基、C2-C4鹵鏈炔基、C3-C6鹵環(huán)烷基、鹵素、CN、NO2、C1-C4烷氧基、C1-C4鹵烷氧基、C1-C4烷硫基、C1-C4烷基亞磺?；?、C1-C4烷基磺酰基、C1-C4烷基氨基、C2-C8二烷基氨基、C3-C6環(huán)烷基氨基、C3-C6(烷基)環(huán)烷基氨基、C2-C4烷基羰基、C2-C6烷氧基羰基、C2-C6烷基氨基羰基、C3-C8二烷基氨基羰基或C3-C6三烷基甲硅烷基；和n是1或2。
5.如權(quán)利要求4的方法，其中每個(gè)R5是R5a或R5b；J取代有R5a并任選取代有1-2個(gè)R5b；R1和R2各自獨(dú)立地是H或C1-C4烷基；R3是任選取代有鹵素、CN、OCH3或S(O)pCH3的C1-C4烷基；R5a基團(tuán)在與K相鄰的位置與J相連；R5a和R5b各自獨(dú)立地是C1-C4烷基、C1-C4鹵烷基、鹵素、CN、NO2、C1-C4烷氧基、C1-C4鹵烷氧基、C1-C4烷硫基、C1-C4烷基亞磺?；?、C1-C4烷基磺?；?、C1-C4鹵烷硫基、C1-C4鹵烷基亞磺?；?、C1-C4鹵烷基磺?；?、C2-C4烷氧基羰基或C3-C8二烷基氨基羰基；或苯基、芐基或者5-或6-元雜芳環(huán)，每個(gè)環(huán)任選取代有1-3個(gè)獨(dú)立地選自R6的取代基；每個(gè)R6獨(dú)立地是鹵素、CN、NO2、C1-C4烷基、C2-C4鏈烯基、C2-C4鏈炔基、C3-C6環(huán)烷基、C1-C4鹵烷基、C1-C4烷氧基或C1-C4鹵烷氧基；和p是0、1或2。
6.如權(quán)利要求5的方法，其中J是苯基、吡唑、吡咯、吡啶或嘧啶。
7.如權(quán)利要求6的方法，其中R1和R2各自是H；一個(gè)R4選自如下基團(tuán)C1-C3烷基、CF3、OCF3、OCHF2、S(O)pCF3、S(O)pCHF2和鹵素，并且任選的第二個(gè)R4選自如下基團(tuán)鹵素、C1-C3烷基和C1-C3鹵烷基。
8.如權(quán)利要求7的方法，其中J是J-1；Q是NR5a；X是N或CH；Y是CH；Z是CR5b；R5a是苯基或2-吡啶基環(huán)，它們?nèi)〈幸粋€(gè)或者兩個(gè)選自如下基團(tuán)的取代基鹵素、C1-C4烷基、C1-C4鹵烷基或C1-C4鹵烷氧基；和R5b是鹵素或CF3。
9.一種式I的化合物，包括其所有幾何異構(gòu)體和立體異構(gòu)體、其N(xiāo)-氧化物或其適用于農(nóng)業(yè)的鹽 其中J是苯環(huán)、萘環(huán)系、5-或6-元雜芳環(huán)或者芳族8-、9-或10-元稠合雜二環(huán)環(huán)系，其中每一環(huán)或環(huán)系取代有一個(gè)R5a并任選取代有1-3個(gè)R5b；K是-C(＝A)NR2-或-NR2C(＝A)-；L是-NR1C(＝B)-R3或-NR1SO2-R3；A和B獨(dú)立地是O或S；R1是H或C1-C4烷基；R2是H或C1-C4烷基；R3是任選取代有鹵素、CN、OCH3或S(O)pCH3的C1-C4烷基；每個(gè)R4獨(dú)立地是C1-C4烷基、C1-C4鹵烷基、鹵素、CN、NO2、C1-C4烷氧基、C1-C4鹵烷氧基、C1-C4烷硫基、C1-C4烷基亞磺?；?、C1-C4烷基磺?；?、C1-C4鹵烷硫基、C1-C4鹵烷基亞磺?；駽1-C4鹵烷基磺酰基；R5a和R5b各自獨(dú)立地是C1-C4烷基、C1-C4鹵烷基、鹵素、CN、NO2、C1-C4烷氧基、C1-C4鹵烷氧基、C1-C4烷硫基、C1-C4烷基亞磺?；?、C1-C4烷基磺?；?、C1-C4鹵烷硫基、C1-C4鹵烷基亞磺?；?、C1-C4鹵烷基磺?；2-C4烷氧基羰基或C3-C8二烷基氨基羰基；或苯基、芐基或者5-或6-元雜芳環(huán)，每個(gè)苯基、芐基和雜芳環(huán)任選取代有1-3個(gè)獨(dú)立地選自R6的取代基；R5a在與K相鄰的位置與J相連；每個(gè)R6獨(dú)立地是鹵素、CN、NO2、C1-C4烷基、C2-C4鏈烯基、C2-C4鏈炔基、C3-C6環(huán)烷基、C1-C4鹵烷基、C1-C4烷氧基或C1-C4鹵烷氧基；n是1、2、3或4；和p是0、1或2；條件是L不是-NHC(＝O)-，并且R3不是取代有一個(gè)或多個(gè)氟部分的C1-C6烷基。
10.如權(quán)利要求9的化合物，其中J是苯環(huán)或者5-或6-元雜芳環(huán)，該雜芳環(huán)選自基團(tuán)J-1、J-2、J-3和J-4，每個(gè)J環(huán)取代有R5a并任選取代有1-2個(gè)R5b Q是O、S或NR5c；W、X、Y和Z獨(dú)立地是N或CR5c，條件是在J-3和J-4中W、X、Y或Z中至少一個(gè)是N；R1和R2各自獨(dú)立地是H或C1-C4烷基；R3是C1-C4烷基，它任選取代有鹵素、CN、OCH3或S(O)pCH3；每個(gè)R4獨(dú)立地是C1-C4烷基、C1-C4鹵烷基、鹵素、CN、NO2、C1-C4烷氧基、C1-C4鹵烷氧基、C1-C4烷硫基、C1-C4烷基亞磺?；1-C4烷基磺?；1-C4鹵烷硫基、C1-C4鹵烷基亞磺酰X基或C1-C4鹵烷基磺?；?；R5a在與K相鄰的位置與J相連；R5a和R5b各自獨(dú)立地是C1-C4烷基、C1-C4鹵烷基、鹵素、CN、NO2、C1-C4烷氧基、C1-C4鹵烷氧基、C1-C4烷硫基、C1-C4烷基亞磺?；?、C1-C4烷基磺?；1-C4鹵烷硫基、C1-C4鹵烷基亞磺酰基、C1-C4鹵烷基磺?；2-C4烷氧基羰基或C3-C8二烷基氨基羰基；或苯基、芐基或者5-或6-元雜芳環(huán)，每個(gè)環(huán)任選取代有1-3個(gè)獨(dú)立地選自R6的取代基；R5c是H或一個(gè)R5a取代基；每個(gè)R6獨(dú)立地是鹵素、CN、NO2、C1-C4烷基、C2-C4鏈烯基、C2-C4鏈炔基、C3-C6環(huán)烷基、C1-C4鹵烷基、C1-C4烷氧基或C1-C4鹵烷氧基；和n是1或2。
11.權(quán)利要求10的化合物，其中J是苯基、吡唑、吡咯、吡啶或嘧啶。
12.權(quán)利要求11的化合物，其中R1和R2各自是H；一個(gè)R4選自如下基團(tuán)C1-C3烷基、CF3、OCF3、OCHF2、S(O)pCF3、S(O)pCHF2和鹵素，并且任選的第二個(gè)R4選自如下基團(tuán)鹵素、C1-C3烷基和C1-C3鹵烷基。
13.權(quán)利要求12的化合物，其中J是J-1；Q是NR5a；X是N或CH；Y是CH；Z是CR5b；R5a是苯基或2-吡啶基環(huán)，它們?nèi)〈幸粋€(gè)或者兩個(gè)選自如下基團(tuán)的取代基鹵素、C1-C4烷基、C1-C4鹵烷基或C1-C4鹵烷氧基；和R5b是鹵素或CF3。
14.一種防治無(wú)脊椎害蟲(chóng)的組合物，其包括生物有效量的如權(quán)利要求1的式I的化合物、其N(xiāo)-氧化物或其適用于農(nóng)業(yè)的鹽；和至少一種選自表面活性劑、固體稀釋劑和液體稀釋劑的其它組分。
15.權(quán)利要求14的組合物，其還包括有效量的至少一種其它生物活性化合物或試劑。
16.權(quán)利要求15的組合物，其中至少一種其它生物活性化合物或試劑選自擬除蟲(chóng)菊酯類(lèi)、氨基甲酸酯類(lèi)、新類(lèi)煙堿類(lèi)、神經(jīng)鈉通道阻斷劑、殺蟲(chóng)的大環(huán)內(nèi)酯、γ-氨基丁酸(GABA)拮抗劑、殺蟲(chóng)的脲類(lèi)和保幼激素模擬物。
17.權(quán)利要求14的組合物，還包括至少一種選自以下的其它生物活性化合物或試劑阿維菌素、乙酰甲胺磷、吡蟲(chóng)清、amidoflumet、齊墩螨素、艾扎丁、甲基保棉磷、氟氯菊酯、聯(lián)苯肼酯、噻嗪酮、呋喃丹、氟唑蟲(chóng)清、定蟲(chóng)隆、毒死蜱、甲基毒死蜱、chromafenozide、clothianidin、氟氯氰菊酯、β-氟氯氰菊酯、氯氟氰菊酯、λ-氯氟氰菊酯、氯氰菊酯、滅蠅胺、溴氰菊酯、殺螨硫隆、二嗪農(nóng)、氟脲殺、樂(lè)果、噁茂醚、emamectin、硫丹、高殺滅菊酯、ethiprole、苯硫威、苯氧威、甲氰菊酯、殺滅菊酯、銳勁特、flonicamid、氟氰戊菊酯、τ-氟胺氰菊酯、氟蟲(chóng)脲、地蟲(chóng)磷、特丁苯酰肼、氟鈴脲、吡蟲(chóng)啉、噁二唑蟲(chóng)、丙胺膦、氟丙氧脲、馬拉硫磷、多聚乙醛、甲胺磷、殺撲磷、滅多蟲(chóng)、烯蟲(chóng)酯、甲氧滴滴涕、久效磷、甲氧苯酰肼、硝蟲(chóng)噻嗪、甲氨叉威、甲氨叉威、對(duì)硫磷、甲基對(duì)硫磷、氯菊酯、甲拌磷、伏殺硫磷、亞胺硫磷、磷胺、抗蚜威、丙溴磷、拒嗪酮、pyridalyl、蚊蠅醚、魚(yú)藤酮、艾克敵105、乙丙硫磷、雙苯酰肼、伏蟲(chóng)隆、七氟菊酯、特丁硫磷、殺蟲(chóng)畏、thiacloprid、thiamethoxam、硫雙威、殺蟲(chóng)雙、四溴菊酯、敵百蟲(chóng)和殺蟲(chóng)隆、涕滅威、甲氨叉威、克線磷、殺螨脒、滅螨猛、乙酯殺螨醇、三環(huán)錫、開(kāi)樂(lè)散、除螨靈、特苯噁唑、喹螨醚、殺螨錫、甲氰菊酯、唑螨酯、噻螨酮、克螨特、噠螨酮、吡螨胺；蘇云金桿菌，包括鲇澤亞種和庫(kù)爾斯塔克亞種，蘇云金桿菌δ毒素、桿狀病毒以及食蟲(chóng)細(xì)菌、病毒和真菌。
18.權(quán)利要求14的組合物，其還包括至少一種選自以下的其它生物活性化合物或試劑氯氰菊酯、氯氟氰菊酯、氟氯氰菊酯和β-氟氯氰菊酯、高氰戊菊酯、殺滅菊酯、四溴菊酯、苯硫威、滅多蟲(chóng)、甲氨叉威、硫雙滅多蟲(chóng)、噻蟲(chóng)胺、吡蟲(chóng)啉、噻蟲(chóng)啉、噁二唑蟲(chóng)、艾克敵105、阿維菌素、齊墩螨素、emamectin、硫丹、ethiprole、銳勁特、氟蟲(chóng)脲、殺蟲(chóng)隆、噁茂醚、蚊蠅醚、拒嗪酮、蟲(chóng)螨脒、蘇云金桿菌、蘇云金桿菌δ毒素和食蟲(chóng)真菌。
全文摘要
本發(fā)明涉及一種防治無(wú)脊椎害蟲(chóng)的方法，包括用生物有效量的式I的化合物(包括所有幾何異構(gòu)體和立體異構(gòu)體)、其N(xiāo)－氧化物或其適用于農(nóng)業(yè)的鹽(例如以包括式I的化合物的組合物)接觸無(wú)脊椎害蟲(chóng)或其環(huán)境，其中J是苯環(huán)、萘環(huán)系、5－或6－元雜芳環(huán)或者芳族8－、9－或10－元稠合雜二環(huán)環(huán)系，其中每一環(huán)或環(huán)系取代有1－4個(gè)R
文檔編號(hào)C07C235/66GK1555364SQ02818247
公開(kāi)日2004年12月15日 申請(qǐng)日期2002年9月17日 優(yōu)先權(quán)日2001年9月21日
發(fā)明者喬治·菲利普·拉姆, 托馬斯·保羅·塞爾比, 保羅 塞爾比, 喬治 菲利普 拉姆 申請(qǐng)人:杜邦公司