本发明属于农药领域。具体地，本发明涉及一种3-芳基氮杂双环衍生物及其制备和杀线虫应用。
技术背景
在世界范围内，植物寄生线虫已经发展成为农林业植物的主要病原体，包括土豆，大豆，番茄等经济作物以及橄榄树，松树等树木。每年由植物寄生线虫侵染所造成的作物产量损失约12％-15％，全球直接农业经济损失达1570亿美元，由于植物寄生线虫的内寄生性，使得其大部分生命周期均在寄主植物体内完成，受寄主植物组织保护，因此难以防治。
迄今为止，超过4100种植物寄生线虫被报道，其中以专性活体营养型根结线虫(meloidogynespp.)毁灭性最大。由于线虫侵染，世界范围内十分之一的蔬菜产量受到影响，其中这些损失的50％则是由根结线虫引起，其危害主要以2龄幼虫(j2)侵染植物根部伸长区部位开始，j2通过口针释放细胞壁裂解酶进入寄主植物根部表皮，进而在内部通过皮层迁移至根尖区对选定的维管束组织细胞进行寄生，通过根结线虫线虫分泌物调节其与寄主细胞间的复杂寄生关系，继而影响寄主细胞的发育与基因表达，使寄主细胞演变成为较大的多核细胞，即巨细胞(giantcell)，以此成为线虫的单一营养供给体。随着巨细胞的发育，临近维管束及皮质细胞增生肥大即形成根节。
松材线虫(bursaphelenchusxylophilus)最初作为北美地区松树生态平衡物种存在，现在已经发展成为日本，朝鲜半岛以及我国等东亚地区森林生态系统的入侵物种，并且正在进一步侵染西班牙与葡萄牙欧洲等地，在我国每年由于松材线虫危害死亡的松树超过100万公顷。松材线虫做为一种迁移性植物内寄生线虫导致松树枯萎病，其严重破坏远东亚地区森林生态系统，松材线虫可经其媒介昆虫松墨天牛(monochamusspp.)携带由死亡松树传播至健康松树上，与同属其他线虫不一样，松材线虫同时具有植食性及噬菌的特点，松材线虫通过树脂管道汲取松树木质部薄壁组织细胞营养，进而导致松树枯萎，当松树死后，松材线虫则开始取食寄生于松树上的葡萄孢属灰葡萄孢菌(botrytiscinerea)
1881年，二硫化碳(cs2)被认为是第一个具有杀线虫活性的产品，20世纪初至20世纪中叶，溴甲烷，氯化苦(cp)，d-d混剂(1,3-d和1,2-d，1942年shell公司)，二溴氯丙烷(dbcp，1955年dour公司)，1,2-二溴乙烯(edb，1946年dow公司)等一些列卤代烃类熏蒸剂出被推出用于线虫防治，1952年，stauffer公司推出棉隆(mylone)用于防治线虫，1955年，stauffer公司继而开发出包括威百亩(vapam)，以及杀线酯(sassen)等产品，这类杀线虫剂能在潮湿的土壤中分解、释放出具有熏蒸作用的异硫氰酸甲酯，硫化氢气体，以及甲醛等成分，从而达到杀线虫的目的。20世纪60年代开始，有机磷、氨基甲酸酯类杀线虫剂逐渐取代熏蒸剂，以灭线磷(ethoprophos)，噻唑膦(fosthiazate，1991)，杀线威(oxamyl，1972)，涕灭威(temik，1962)为代表的高效非熏蒸类杀线虫剂被推出，这类杀线虫剂主要作用于线虫神经系统的乙酰胆碱酯酶(ache)，导致虫体神经传导受阻，造成线虫生理活动紊乱，进而死亡。
由于环境压力，高毒性、长期使用造成线虫抗性的不断提升、对非靶标生物神经毒性等的一些影响，致使一些杀线虫剂慢慢在市场上被逐步淘汰，甚至有些已经被禁用，目前可供选择的杀线虫剂种类较少，新颖杀线剂的开发仍不可或缺。
技术实现要素：
本发明的目的是提供一类3-芳基氮杂双环的衍生物的制法和杀线虫应用，尤其是在植物寄生线虫领域的应用，从而起到保护植物的作用。
本文描述的杀线虫组合物包含有效量的具有任何本文描述的式的化合物或化合物的混合物，例如下面显示的化合物。
本发明的第一方面，提供通式i所示的化合物、或其光学异构体，顺反异构体、农药学上可接受的盐。
其中，
r为氢、取代的或未取代的c1～c15烷基、取代的或未取代的c3～c7环烷基，取代的或未取代的c2～c6烯基、取代的或未取代的c2～c6炔基、取代的或未取代的c1～c15烷氧基、取代或未取代的5元或6元杂芳环、羰基-c6-c10芳基-c1～c15烷基、c1～c15烷氧基羰基、c6-c10芳基c1～c15烷氧基羰基；所述取代的是指被选自下组的一个或多个取代基所取代：卤素、氰基、硝基、羟基、氨基、c1～c6烷基、卤代c1～c6烷基、c1～c6烷氧基、羧基、c6-c10芳基；
x1为ch＝ch或不存在，x2为ch＝ch或不存在，且当x1为ch＝ch时，不存在x2；当x2为ch＝ch，不存在x1；
a为n、s或ch；
b为n或c；
d为ch、n、o或s；
e为c、n、o或ch；
ar是苯环、萘环、5-6元杂芳环或8-12元杂芳二环环系；r1为ar上的取代基，数量为0、1、2、3或4个，各r1各自独立地选自：c1～c6烷基、c1～c6烷氧基、卤素、卤代c1～c6烷基、卤代c1～c6烷氧基、氰基、硝基、c6-c10芳基、5元或6元杂芳基，或-oar1；其中ar1为c6-c10芳基、5元或6元杂芳基或8-12元杂芳二环环系；其中，c6-c10芳基、5元或6元杂芳基任选地被选自下组的1、2、3或4个取代基取代：卤素、氰基、硝基、羟基、氨基、c1～c6烷基、卤代c1～c6烷基、c1～c6烷氧基。
在另一优选例中，r为取代的或未取代的c1～c4烷基或取代的或未取代的c1～c4烷氧基羰基；所述取代的是指被选自下组的1、2或3个取代基所取代：卤素、氰基、硝基、羟基、氨基、c1～c4烷基、卤代c1～c4烷基、c1～c4烷氧基、羧基、苯基。
在另一优选例中，当d为s或o、b为c、a为n，e为n或c(h)时，x1和x2不存在。
在另一优选例中，当d为s时，b为c，a为n，e为n或c(h)，x1和x2不存在。
在另一优选例中，当d为o时，b为c，a为n，e为n，x1和x2不存在。
在另一优选例中，当d为n、b为c、a为s或n、e为ch或o时，x1和x2为不存在。
在另一优选例中，当d为n时，b为c，a为s，e为ch，x1和x2为不存在。
在另一优选例中，当d为n时，b为c，a为n，e为o，x1和x2为不存在。
在另一优选例中，当d为ch或n、b为n、a为ch或n、e为c时，x2为ch＝ch。
在另一优选例中，当d为c、b为n、a为n、e为ch时，x1为ch＝ch。
在另一优选例中，当d为ch或n、b为n、a为ch或n、e为ch时，x1和x2为不存在。
在另一优选例中，当d为n，b为n，a为ch，e为ch时，x1和x2为不存在。
在另一优选例中，当d为n，b为n，a为ch，e为c时，x为ch＝ch。
在另一优选例中，当d为ch、b为n、a为n、e为c时，x为ch＝ch。
在另一优选例中，当d为ch、b为n、a为n、e为ch，x1和x2为不存在。
在另一优选例中，所述化合物具有如下所示结构，
式中ar的定义如权利要求1中所述，任选地具有1、2或3个取代基r1；r、r1的定义如权利要求1中所述。
在另一优选例中，ar是苯环、萘环、5-6元杂芳环或8-10元杂芳二环环系，任选地具有1、2或3个取代基r1；
各式中，各r1各自独立地选自：c1～c6烷基、c1～c4烷氧基、氟、氯、溴、卤代c1～c4烷基、卤代c1～c4烷氧基、氰基、硝基、苯基、5元或6元杂芳基、-o-苯基、-o-5元或6元杂芳基；其中，苯基、5元或6元杂芳基任选地被选自下组的1或2个取代基取代：卤素、氰基、硝基、羟基、氨基、c1～c4烷基、卤代c1～c4烷基、c1～c4烷氧基。
在另一优选例中，所述化合物具有4aa-52ac之一所示的结构。
本发明的第二方面，提供一种农药组合物，包含第一方面所述的化合物或其农药学上可接受的盐；和农药学上可接受的载体。
本发明的第三方面，提供第一方面所述的化合物或其农药学上可接受的盐或第二方面所述的农药组合物的用途，用于杀线虫或预防线虫；或者用于制备杀线虫或预防线虫的药剂。
本发明的第四方面，提供一种杀线虫或预防线虫的方法，所述方法包括将第一方面所述的化合物或其农药学上可接受的盐或第二方面所述的农药组合物施加于遭受或可能遭受虫害的植物体或其周围的土壤或环境中。
本发明的提供一种杀线虫或预防线虫方法，所述方法包括将第一方面所述氮杂双环衍生物或其农药学上可接受的盐或第二方面所述组合物施加于遭受或可能遭受虫害的植物体或其周围的土壤或环境中。
在另一优选例中，所述氮杂双环衍生物或其农药学上可接受的盐或所述农药组合物的施用浓度为0.05-200ppm；较佳地，为0.1-100ppm；更佳地，为0.5-50ppm。
在另一优选例中，所述线虫包括但不局限于松材线虫、根结线虫、甜菜包囊线虫、马铃薯金线虫、大豆包囊线虫，甘薯茎线虫，粟线虫、水稻子尖线虫。
应理解，在本发明范围内中，本发明的上述各技术特征和在下文(如实施例)中具体描述的各技术特征之间都可以互相组合，从而构成新的或优选的技术方案。限于篇幅，在此不再一一累述。
具体实施方式
本发明人经过广泛而深入的研究，首次合成了一类结构新颖的氮杂双环类衍生物，这类化合物具有优异的杀线虫活性，在此基础上，发明人完成了本发明。
基本定义
术语“c1～c15烷基”指具有1-15个碳原子的直链或支链的烷基，例如甲基、乙基、正丙基、异丙基、1-丁基、2-丁基、戊基、己基、庚基、辛基、壬基、癸基或类似基团。可优选c1～c6烷基。
术语“c1～c15烷氧基”指具有1-15个碳原子的直链或支链的烷基，例如甲氧基、乙氧基、正丙氧基、异丙氧基、1-丁氧基、2-丁氧基、戊氧基、己氧基、庚氧基、辛氧基、壬氧基、癸氧基或类似基团。可优选c1～c6烷基。
术语“c2～c6烯基”指具有2-6个碳原子的直链或支链的烯基，例如乙烯基、正丙烯基、异丙烯基、1-丁烯基、2-丁烯基、戊烯基、己烯基或类似基团。可优选c2～c4烯基。
术语“c2～c6炔基”指具有2-6个碳原子的直链或支链的炔基，例如乙炔基、正丙炔基、异丙炔基、1-丁炔基、2-丁炔基、戊炔基、己炔基或类似基团。可优选为c2～c4炔基。
术语“c3～c7环烷基”指具有3-7个碳原子的环状烷基，例如环丙基、环丁基、环戊基、环己基或环庚基。
术语“环”或“环系”指碳环或杂环。
术语“杂环”指形成所述杂环骨架的原子中至少一个不是碳，为氮、氧或硫，且杂环为饱和或部分不饱和的非芳香性杂环，优选地，杂原子的数量为1、2、3或4个。
术语“5元或6元杂芳环”指含有一个或多个选自碳、氮、氧或硫的杂原子的五元或六元环，例如苯基、吡啶基、呋喃基、噻吩基、噻唑基、吡咯基、咪唑基、吡唑基、嘧啶基、噁唑基、哌嗪基、三嗪基、噻二唑基、噁二唑基、三唑基等。
术语“8-12元杂芳二环环系”可选自：萘基、苯并呋喃基、喹啉基、吲哚基、苯并噻吩、异喹啉基，苯并噻吩、苯并噻唑、苯并吡唑、苯并咪唑、苯并噁唑、苯并-[1,3]-二氧杂环戊基等。
术语“卤素”为氟、氯、溴、碘。所述“卤代”为氟代、氯代、溴代、碘代。
术语“本发明的活性物质”或“本发明的活性化合物”是指本发明化合物或其农药学上可接受的盐。
所述农药学上可接受的盐可以包括无机盐、有机酸盐、碱性氨基酸或酸性氨基酸的盐。本发明中无机酸盐包括例如：盐酸、氢硼酸、硝酸、硫酸或磷酸。本发明中有机酸包括例如：乳酸、甲酸、乙酸(即醋酸)、三氟乙酸、延胡索酸、草酸、马来酸、柠檬酸、琥珀酸、苹果酸、甲磺酸、苯磺酸、或对甲苯磺酸。酸性氨基酸包括例如：甘氨酸、天冬氨酸、或谷氨酸。
本发明化合物尤其对植物寄生线虫有特效。
含本发明活性物质的杀线虫剂组合。
可将本发明的活性物质以常规的方法制备成杀虫剂组合物。这些活性化合物可做成常规的制剂，例如溶液剂，乳剂，混悬剂，粉剂，泡沫剂，糊剂，颗粒剂，气雾剂等制剂。
这些制剂可用已知的方法生产，例如，将活性化合物与扩充剂混合，这些扩充剂就是液体的或液化气的或固体的稀释剂或载体，并可任意选用表面活性剂即乳化剂和/或分散剂和/或泡沫形成剂。例如在用水作扩充剂时，有机溶剂也可用作助剂。
用液体溶剂作稀释剂或载体时，基本上是合适的，如：芳香烃类，例如二甲苯，甲苯或烷基萘；氯化的芳香或氯化的脂肪烃类，例如氯苯，氯乙烯或二氯甲烷；脂肪烃类，例如环己烷或石蜡，例如矿物油馏分；醇类，例如乙醇或乙二醇以及它们的醚和脂类；酮类，例如丙酮，甲乙酮，甲基异丁基酮或环已酮；或不常用的极性溶剂，例如二甲基甲酰胺和二甲基亚砜，以及水。
就液化气的稀释剂或载体说，指的是在常温常压下将成为气体的液体，例如气溶胶推进剂，如卤化的烃类以及丁烷，丙烷，氮气和二氧化碳。
固体载体可用磨碎的天然的矿物质，例如高岭土，粘土，滑石，石英，活性白土，蒙脱土，或硅藻土，和磨碎的合成的矿物质，例如高度分散的硅酸，氧化铝和硅酸盐。供颗粒用的固体载体是碾碎的和分级的天然告石，例如方解石，大理石，浮石，海泡石和白云石，以及无机和有机粗粉合成的颗粒，和有机材料例如锯木屑，椰子壳，玉米棒子和烟草梗的颗粒等。
非离子的和阴离子的乳化列可用作乳化剂和/或泡沫形成剂。例如聚氧乙烯-脂肪酸酯类，聚氧乙烯-脂肪醇醚类，例如烷芳基聚乙二醇醚类，烷基磺酸酯类，烷基硫酸酯类，芳基磺酸酯类以及白蛋白水解产物。分散剂包括，例如木质素亚硫酸盐废液和甲基纤维素。
在制剂中可以用粘合剂，例如羧甲基纤维素和以粉末，颗粒或乳液形式的天然和合成的多聚物，例如阿拉伯胶，聚乙烯基醇和聚乙烯醋酸酯。
可以用着色剂例如无机染料，如氧化铁，氧化钻和普鲁士蓝；有机染料，如有机染料，如偶氯染料或金属钛菁染料；和用痕量营养剂，如铁，猛，硼，铜，钴，铝和锌的盐等。
这些制剂通常含有占所述杀虫剂组合物0.001-99.99重量％，优选0.01-99.9重量％，更优选0.05-90重量％的本发明的活性化合物。从商品制剂制成使用剂型中的活性化合物的浓度可在广阔的范围内变动。使用剂型中的活性化合物的浓度可从0.0000001-100％(g/v)，最好在0.0001与1％(g/v)之间。
下面结合具体实施例，进一步阐述本发明。应理解，这些实施例仅用于说明本发明而不用于限制本发明的范围。下列实施例中未注明具体条件的实验方法，通常按照常规条件，或按照制造厂商所建议的条件。除非另外说明，否则百分比和份数按重量计算。
本发明提供了一种氮杂双环衍生物的制备方法，包括步骤：
在惰性溶剂中(如乙腈、甲醇、异丙醇、乙醇、dmf等)，将化合物a1和化合物a2进行反应，得到化合物a3
式中，r、ar定义同前。
或所述方法包括步骤：
(1)在惰性溶剂中(如乙腈、甲醇、异丙醇、乙醇、n,n-二甲基甲酰胺、n,n-二甲基乙酰胺、水，甲苯、二甲基亚砜等)，将化合物b1和化合物b2进行反应，得到化合物b3；
(2)在惰性溶剂中(如乙腈、甲醇、异丙醇、乙醇、n,n-二甲基甲酰胺、n,n-二甲基乙酰胺、水，甲苯、二甲基亚砜等)，将化合物b4和化合物b5进行反应，得到化合物b3.
式中，r、ar定义同前。
或者所述方法包括步骤：在惰性溶剂中(如二氯甲烷、乙酸乙酯、四氢呋喃、n,n-二甲酰胺、二氧六环、二氯乙烷、氯仿、甲苯、二甲苯、二甲基亚砜等)，将化合物c1和化合物c2进行反应，得到化合物c3；
式中，r、ar定义同前。
或者所述方法包括步骤：在惰性溶剂中(如二氯甲烷、乙酸乙酯、四氢呋喃、n,n-二甲酰胺、二氧六环、二氯乙烷、氯仿、甲苯、二甲苯、二甲基亚砜等)，将化合物d1和化合物c2进行反应，得到化合物d3；
式中，r、ar定义同前。
或者所述方法包括步骤：在惰性溶剂中(如二氯甲烷、乙酸乙酯、四氢呋喃、n,n-二甲酰胺、二氧六环、二氯乙烷、氯仿、甲苯、二甲苯、二甲基亚砜等)，将化合物d1和化合物c2与劳森试剂进行反应，得到化合物e3；
式中，r、ar定义同前。
或者所述方法包括步骤：在惰性溶剂中(如二氯甲烷、乙酸乙酯、四氢呋喃、n,n-二甲酰胺、二氧六环、二氯乙烷、氯仿、甲苯、二甲苯、二甲基亚砜等)，将化合物f1和化合物f2在碱性(如三乙胺、碳酸钾、碳酸钠、氢氧化钾，氢氧化钠、甲醇钠、乙醇钠、叔丁醇钾、氢化钠等)条件下进行反应，得到化合物f3
式中，r、ar定义同前。
或者所述方法包括步骤：在惰性溶剂中(如二氯甲烷、乙酸乙酯、四氢呋喃、n,n-二甲酰胺、二氧六环、二氯乙烷、氯仿、甲苯、二甲苯、二甲基亚砜等)，将化合物f1和化合物g2在碱性(如三乙胺、碳酸钾、碳酸钠、氢氧化钾，氢氧化钠、甲醇钠、乙醇钠、叔丁醇钾、氢化钠等)条件下进行反应，得到化合物g3
式中，r、ar定义同前。
或者所述方法包括步骤：在惰性溶剂中(如二氯甲烷、乙酸乙酯、四氢呋喃、n,n-二甲酰胺、二氧六环、二氯乙烷、氯仿、甲苯、二甲苯、二甲基亚砜等)，将化合物f1和化合物h2在碱性(如三乙胺、碳酸钾、碳酸钠、氢氧化钾，氢氧化钠、甲醇钠、乙醇钠、叔丁醇钾、氢化钠等)条件下进行反应，得到化合物h3和h4
式中，r、r1定义同前。
或者所述方法包括步骤：在惰性溶剂中(如二氯甲烷、乙酸乙酯、四氢呋喃、n,n-二甲酰胺、二氧六环、二氯乙烷、氯仿、甲苯、二甲苯、二甲基亚砜等)，将化合物f1和化合物i2在碱性(如三乙胺、碳酸钾、碳酸钠、氢氧化钾，氢氧化钠、甲醇钠、乙醇钠、叔丁醇钾、氢化钠等)条件下进行反应，得到化合物i3和i4；
式中，r、r1定义同前。
下面更具体地描述本发明化合物的制备方法，但这些具体方法不对本发明构成任何限制。本发明化合物还可以任选将在本说明书中描述的或本领域已知的各种合成方法组合起来而方便的制得，这样的组合可由本发明所属领域的技术人员容易的进行。
中间体的制备：
式中，ar定义同前。
实施例1：中间体2的制备。
在500ml圆底烧瓶中依次加入40.0mmol托品酮1，60.0mmol叔丁醇，300ml四氢呋喃，将反应液置于冰水浴中，搅拌并降温至0℃，随后一次性加入80mmol叔丁醇钾，并保持0℃继续搅拌10min，将60.0mmol对甲苯磺酰甲基异腈溶于60ml四氢呋喃中并慢慢滴加至反应液中，待滴加完毕，反应液继续保持0℃搅拌30min，之后转至室温反应6h，反应结束后，旋转蒸发脱除溶剂，加入125ml去离子水，二氯甲烷萃取(3×50ml)，合并有机相，减压除去溶剂得到粗产物，经柱色谱分离得到5.4g无色油状物，产率89％；1hnmr(400mhz,cdcl3)δ3.20–3.18(m,2h),2.73(tt,j＝12.1,5.6hz,1h),2.28(s,3h),2.09–2.05(m,2h),2.00(dd,j＝12.7,2.1hz,2h),1.78(ddd,j＝13.4,5.3,3.3hz,2h),1.53(dd,j＝14.9,6.5hz,2h).13cnmr(101mhz,cdcl3)δ122.31,60.07,40.10,34.29,25.62,20.07.ms(gc-ms):c9h14n2[m]+m/z150.1.
实施例2：中间体3的制备。
向350ml反应瓶中，依次加入20.0mmol化合物2，150ml吡啶，30.0mmol20％硫化铵水溶液，将反应液缓慢升温至55℃反应48h，反应完毕，旋转蒸发除去溶剂后将反应残渣溶于100ml冰水中并用饱和碳酸钠水溶液调节ph至8-9，过滤，滤饼干燥后可直接用于下一步反应。淡黄色固体2.1g，产率58％；1hnmr(400mhz,dmso-d6)δ9.28(s,1h),9.11(s,1h),3.13(br,s,2h),2.85(tt,j＝11.4,5.2hz,1h),2.21(s,3h),1.99–1.92(m,4h),1.57–1.52(m,2h),1.41–1.36(m,2h)ppm.13cnmr(101mhz,dmso-d6)δ212.23,60.73,49.04,42.15,36.23,26.33ppm.hrms(ei-tof)calcdforc9h16n2s[m+]m/z184.1034,found184.1035.
实施例3：目标产物4的制备。
在10ml圆底烧瓶中，依次加入1mmol中间体3和1.1mmolα-溴代芳基乙酮，加入5ml无水乙醇并将反应液加热至回流后反应3h，反应结束后，旋转蒸发除去溶剂，粗产物通过快速色谱纯化得到目标化合物4。
式中，ar定义同前。
实施例4：中间5的制备。
向100ml圆底烧瓶中依次加入10mmol化合物3，15mmol醋酸钠，50ml醋酸，13mmol40％氯乙醛水溶液，搅拌并缓慢升温至80℃反应12h，反应结束，减压除去溶剂，向反应残渣中加入30ml去离子水并用饱和碳酸钠水溶液调节ph至8-9，二氯甲烷萃取(3×30ml)，合并有机相，减压除去溶剂得到粗产物，柱色谱分离得到1.30g褐色油状物,产率63％。1hnmr(400mhz,cdcl3)δ7.56(d,j＝3.3hz,1h),7.14(d,j＝3.3hz,1h),3.48–3.47(m,2h),3.36(tt,j＝12.0,5.5hz,1h),2.46(s,3h),2.31–2.24(m,2h),2.18–2.14(m,2h),1.93(ddd,j＝14.5,5.1,3.3hz,2h),1.79(dd,j＝14.7,6.1hz,2h)ppm.13cnmr(101mhz,cdcl3)δ173.98,141.92,118.21,61.74,39.05,36.64,32.77,25.62ppm.ms(gc-ms):c9h16n2s[m]+m/z208.1.
实施例5：目标产物6的制备。
将2mmol碳酸银,0.05mmol[1,1’-双(二苯基膦)二茂铁]二氯化钯二氯甲烷络合物，0.1mmol三苯基膦,1.2mmol芳基碘代物依次加入25ml三口玻璃反应器中，之后加入1mmol化合物5，去离子水10ml，将反应器放置于微波合成仪中，插入超声探头，调节探头高度使其浸于液面下方2-3mm处，接通冷凝水，调整微波功率60w，超声功率75w，反应1.5小时，待原料反应完全，反应液冷却至室温，将反应液转移至125ml分液漏斗，二氯甲烷萃取(3×30ml)，萃取液经硅藻土过滤，合并萃取液，旋转蒸发脱除溶剂，柱色谱分离得到目标化合物6。
式中，ar定义同前。
实施例6：中间体8的制备。
以化合物7为反应原料，具体实施方法同上述中间体2的制备。1hnmr(400mhz,cdcl3)δ4.28–4.23(m,2h),2.98(tt,j＝11.9,5.5hz,1h),2.08–1.92(m,4h),1.88–1.84(m,2h),1.65–1.59(m,2h),1.48(s,9h)ppm.13cnmr(101mhz,cdcl3)δ152.98,121.64,79.92,52.67,52.00,34.19,33.51,28.43,27.85,27.16,20.64ppm.
实施例7：中间体9的制备。
向100ml圆底烧瓶中依次加入10mmol中间体8，15mmol盐酸羟胺，20.0mmol碳酸氢钠，40ml乙醇，8ml去离子水，反应液在室温状态下搅拌反应1h，之后将反应液加热回流继续反应8h，反应结束后，旋转蒸发脱除溶剂，反应残渣溶于20ml去离子水，乙酸乙酯萃取(3×20ml)，合并萃取液，减压除去溶剂得到粗产物可直接用于下一步反应。
实施例8：中间体10的制备。
向50ml圆底烧瓶中依次加入2mmol化合物9，3mmol芳基甲酸，10mmol三乙胺，5.0mmol1-丙基环磷酸酐，20ml乙酸乙酯，反应液用氮气置换三次，并于氮气氛围下回流反应8h，反应结束后，旋转蒸发除去乙酸乙酯，反应残渣溶于20ml去离子水，并用饱和碳酸钠水溶液调节ph至8-9，乙酸乙酯萃取(20ml×3)，合并萃取液，粗产物经柱色谱分离得到中间体10。
实施例9：目标产物11的制备。
向25ml圆底烧瓶中依次加入1mmol化合物10，10ml二氯甲烷及2ml三氟乙酸，室温搅拌反应5h，反应结束后，旋转蒸发除去溶剂，反应残渣溶于10ml去离子水中，并用饱和碳酸钠水溶液缓慢调节ph至8-9，二氯甲烷萃取(20ml×3)，合并萃取液，旋转蒸发脱除溶剂后，依次加入5mmol37％甲醛水溶液，10mmol乙酸，5mmol锌屑，溶剂去离子水10ml，将反应液置于100℃油浴反应12h，反应结束后，缓慢加入饱和na2co3水溶液调节反应液ph至8-9，二氯甲烷萃取(20ml×4)，合并萃取液，旋转蒸发脱除溶剂后，经柱色谱分离得到目标产物11
式中，ar定义同前。
实施例10：中间体13的制备。
向250ml圆底烧瓶中依次加入40mmol去甲基托品酮盐酸盐12，45mmol苄溴，150ml乙腈，室温状态下搅拌，加入100mmol碳酸钾，之后将反应液加热至回流继续反应8h，反应结束，待反应液冷却至室温，抽滤，滤饼用乙酸乙酯洗涤(10ml×3)，滤液经旋转蒸发除去溶剂，粗产物经柱色谱分离得到7.5g无色油状物中间体13，87％产率，1hnmr(400mhz,cdcl3)δ7.40(d,j＝7.4hz,2h),7.32(t,j＝7.4hz,2h),7.24(t,j＝7.3hz,1h),3.72(s,2h),3.45(br,s,2h),2.66(dd,j＝16.0,4.2hz,2h),2.19–2.15(m,2h),2.10–2.06(m,2h),1.59(dd,j＝14.7,6.7hz,2h)ppm.13cnmr(101mhz,cdcl3)δ210.09,139.39,128.44,128.38,127.12,58.59,55.13,48.24,27.86ppm.
实施例11：中间体14的制备。
以中间体13为反应原料，具体实施步骤同上述中间体2的制备。1hnmr(400mhz,cdcl3)δ7.35–7.29(m,4h),7.26–7.22(m,1h),3.49(s,2h),3.23(br,s,2h),2.91(t,j＝7.7hz,1h),2.18–2.07(m,6h),1.84–1.81(m,2h)ppm.13cnmr(101mhz,cdcl3)δ128.55,128.28,126.98,124.83,58.47,57.04,33.50,25.52,19.10ppm.
实施例12：中间体15的制备。
向250ml圆底烧瓶中依次加入20mmol中间体14，100ml去离子水，20ml浓盐酸，反应液加热至回流反应48h，反应结束，待反应液冷却至室温，减压除去盐酸与水，得到褐色粘稠状粗产物可直接用于下一步反应。
实施例13：中间体16的制备。
将上述所得中间体15全部转移至250ml圆底烧瓶中，加入4mmol对甲苯磺酸，100ml无水乙醇，加热至回流反应8h，反应结束后，待反应液冷却至室温，旋转蒸发除去乙醇，粗产物经柱色谱分离得到4.8g油状物，产率88％。1hnmr(400mhz,cdcl3)δ7.39(d,j＝7.6hz,2h),7.30(t,j＝7.4hz,2h),7.22(t,j＝7.2hz,1h),4.11(q,j＝7.1hz,2h),3.56(s,2h),3.23(br,s,2h),2.61(tt,j＝11.9,5.6hz,1h),2.05–2.02(m,2h),1.94(t,j＝12.1hz,2h),1.65–1.56(m,4h),1.23(t,j＝7.1hz,3h)ppm.13cnmr(101mhz,cdcl3)δ175.75,139.86,128.53,128.17,126.76,60.25,58.47,56.16,34.85,33.51,26.56,14.28ppm.
实施例14：中间体17的制备。
向250ml圆底烧瓶中依次加入30mmol中间体16，45mmol80％水合肼，80ml无水乙醇，将反应液加热至回流状态，搅拌反应48h，反应完成后待反应液冷却至室温，旋转蒸发除去乙醇得到白色固体粗产物，粗产物经冷水洗涤三次，过滤，得到白色固体，干燥后可直接用于下一步反应。白色固体4.6g,60％产率。1hnmr(400mhz,dmso-d6)δ8.88(br,s,1h),7.35(d,j＝7.0hz,2h),7.31(t,j＝7.4hz,2h),7.22(t,j＝7.0hz,1h),4.13(br,s,2h),3.49(s,2h),3.11(br,s,2h),2.44(tt,j＝11.6,5.4hz,1h),1.98–1.96(m,2h),1.81–1.74(m,2h),1.53(dd,j＝13.6,5.8hz,2h),1.37–1.32(m,2h)ppm.13cnmr(101mhz,dmso-d6)δ174.07,140.08,128.24,128.03,126.51,58.19,55.51,33.71,33.44,26.16ppm.
实施例15：中间体18的制备。
向50ml圆底烧瓶中依次加入2mmol化合物17，3mmol芳基甲酸，5mmol三乙胺，5mmol1-丙基环磷酸酐，20ml乙酸乙酯，反应液用氮气置换三次，并于氮气氛围下回流反应8h，反应结束后，冷却至室温，旋转蒸发除去乙酸乙酯，反应残渣溶于20ml去离子水，并用饱和碳酸钠水溶液调节ph至8-9，乙酸乙酯萃取(20ml×3)，合并萃取液，萃取液经旋转蒸发脱除溶剂，柱色谱分离得到目标产物。
实施例16：中间体19的制备。
向25ml圆底烧瓶中依次加入1mmol化合物18，10ml无水乙腈，2ml三氯氧磷，反应液加热至回流状态搅拌反应12h，反应结束后，冷却至室温，缓慢加入5ml去离子水，并继续搅拌10min，之后向反应液中缓慢滴加饱和碳酸钠水溶液调节反应液ph至8-9，旋转蒸发除去乙腈，反应残渣溶于10ml去离子水中，并用二氯甲烷萃取(3×20ml)，合并萃取液，萃取液经旋转蒸发脱除溶剂，柱色谱分离得到目标产物。
实施例17：目标化合物20的制备。
向25ml圆底烧瓶中依次加入0.5mmol中间体19，10ml无水甲醇，100.0mg10％钯炭，5.0mmol甲酸铵，室温状态下搅拌反应过夜，反应结束后，反应液经硅藻土抽滤，滤液经旋蒸除去溶剂后，溶于10ml去离子水，并用二氯甲烷萃取(10ml×3)，合并萃取液并除去溶剂后，依次加入2.5mmol锌屑，2.5mmol37％甲醛水溶液，5mmol乙酸，10ml去离子水，将反应液置于100℃反应12h，反应完成后，待反应液冷却至室温，用饱和碳酸钠溶液调节反应液ph至8-9，反应液经二氯甲烷萃取(20ml×3)，合并萃取液，减压除去溶剂，柱色谱分离得到目标化合物20。
实施例18：中间体21的制备。
向50ml圆底烧瓶中依次加入2mmol中间体18，20ml无水甲醇，400.0mg10％钯炭，5mmol甲酸铵，室温状态下搅拌反应过夜，反应结束后，反应液经硅藻土抽滤，滤液经旋蒸除去溶剂后，溶于20ml去离子水，并用二氯甲烷萃取(20ml×3)，合并萃取液并除去溶剂后，粗产物无需柱色谱分离可直接用于下一步反应。
实施例19：中间体22的制备。
向50ml圆底烧瓶中依次加入1.5mmol中间体21，20ml甲苯，4mmol劳森试剂，反应液加热至回流状态反应12h，待原料反应完全，反应液冷却至室温，加入20ml去离子水，并用乙酸乙酯萃取(20ml×3)，合并萃取液并除去溶剂后，粗产物经柱色谱分离后用于下一步反应。
实施例20：目标化合物23的制备。
向25ml圆底烧瓶中依次加入0.5mmol中间体22，2.5mmol锌屑，2.5mmol37％甲醛水溶液，5mmol乙酸，10ml去离子水，将反应液置于100℃反应12h，反应完成后，待反应液冷却至室温，用饱和碳酸钠溶液调节反应液ph至8-9，反应液经二氯甲烷萃取(20ml×3)，合并萃取液，减压除去溶剂，柱色谱分离得到目标化合物。
式中，r定义同前。
实施例21：中间体25的制备。
向250ml圆底烧瓶中依次加入150ml二氯甲烷，40mmol化合物24，之后依次加入60mmol咪唑，52mmol三苯基膦，搅拌并降温至0℃，随后一次性加入48mmol碘单质，继续0℃搅拌反应30min，之后转至室温反应过夜，反应完成后，抽滤除去不溶物，滤饼用二氯甲烷洗涤(20ml×3)，合并滤液，减压除去溶剂，向反应残渣中加入去离子水30ml，加入饱和碳酸钠水溶液调节ph至8-9，并用二氯甲烷萃取(50ml×3)，萃取液减压除去溶剂，粗产物经柱色谱分离得到目标产物。
式中，ar定义同前。
实施例22：中间体27的制备。
向100ml圆底烧瓶中依次加入5mmol化合物26，7.5mmoln,n-二甲基甲酰胺二甲基缩醛，20ml无水乙醇，加热至回流反应48h，反应结束后，反应液冷却至室温，减压除去乙醇，反应残渣溶于50ml乙酸乙酯，并用饱和食盐水洗涤(20ml×3)，有机相经减压除去溶剂，得到的粗产物可直接用于下一步反应。
实施例23：中间体28的制备。
向50ml圆底烧瓶中依次加入3mmol中间体27，4.5mmol盐酸肼，0.6mmol对甲苯磺酸，20ml无水乙醇，加热至回流反应6-8h，反应结束后，反应液冷却至室温，减压除去乙醇，反应残渣溶于30ml去离子水，乙酸乙酯萃取(30ml×3)，合并萃取液，粗产物经柱色谱分离得到目标产物。
实施例24：中间体29的制备。
向25ml圆底烧瓶中依次加入2mmol中间体28，10ml无水n,n-二甲基甲酰胺，5mmol氢化钠，反应液在氮气氛围下室温反应10min，之后加入3mmol中间体25，并将反应液缓慢升温至70℃继续反应12h，反应结束后，待反应液冷却至室温，缓慢滴加1.0ml去离子水淬灭剩余氢化钠，反应液转移至分液漏斗，加入去离子水(20ml)，并用乙酸乙酯萃取(20ml×3)，合并萃取液，，旋转蒸发脱除溶剂后进行柱色谱分离得到目标产物。
实施例25：目标化合物30的制备。
以中间体29为反应原料，当r基团为苄基或苄氧羰基时，具体实施步骤同上述目标产物20的制备方法；当r基团为叔丁氧羰基时，具体实施步骤同上述目标产物11的制备方法。
式中，r、ar定义同前。
实施例26：中间体32的制备。
以4-溴-1-h-吡唑31和中间体25在碱性条件下反应而得，具体实施方法同上述中间体29的制备方法。
实施例27：中间体33的制备。
向25ml圆底烧瓶中依次加入2mmol中间体32，3mmol芳基硼酸，4mmol碳酸钾，0.1mmol四三苯基膦钯，之后加入10ml甲苯，1ml无水乙醇和1ml去离子水，将反应液置于90℃回流反应16h，反应结束后，待反应液冷却至室温，减压除去溶剂，反应残渣溶于20ml去离子水，乙酸乙酯萃取(20ml×3)，合并萃取液，粗产物经柱色谱分离得到目标产物。
实施例28：目标化合物34的制备。
中间体33为反应原料，当r基团为叔丁氧羰基时，具体实施步骤同上述目标产物11的制备方法。
式中，r、r1定义同前。
实施例29：中间体36的制备。
向25ml圆底烧瓶中依次加入20mmoln-甲基-5-羟基吡唑35，6.0ml无水n,n-二甲基甲酰胺，将反应液置于冰水浴中搅拌降温至0℃后，随后将6.0ml三溴化磷缓慢滴加至反应液中，滴加完毕保持0℃继续反应10min，之后将反应温度缓慢升高至80℃继续反应8h，反应结束后，待反应液降至室温，向反应液中缓慢加入20ml去离子水至粘稠状反应液完全溶解，并用饱和碳酸钠水溶液缓慢调节ph至8-9，反应液经乙酸乙酯萃取(30ml×3)，并用饱和食盐水洗涤萃取液(20ml×3)，萃取液经旋转蒸发除去溶剂，粗产物经柱色谱分离得到目标产物。1hnmr(400mhz,cdcl3)δ9.77(s,1h),7.97(s,1h),3.93(s,3h)ppm.
实施例30：中间体41的制备。
向100ml圆底烧瓶中依次加入10.0mmol1-甲基-1h-吡唑-5-甲醛40，20ml反应溶剂n,n-二甲基甲酰胺，室温状态下搅拌至原料溶解，随后将11mmoln-溴代丁二酰亚胺溶于10mln,n-二甲基甲酰胺后缓慢滴加至反应液中，将反应液置于室温继续搅拌反应18h，反应结束后加入10ml20％氢氧化钠水溶液并继续搅拌10min，之后向反应液中加入50ml去离子水，乙酸乙酯萃取(30ml×3)，合并萃取液并用饱和食盐水洗涤(20ml×3)，萃取液经旋转蒸发除去溶剂，粗产物经柱色谱分离得到目标产物。1hnmr(400mhz,cdcl3)δ9.87(s,1h),7.50(s,1h),4.14(s,3h)ppm.
实施例31：中间体37及中间体42的制备。
分别以中间体36或中间体41为反应原料，具体实施步骤同上述中间体33的合成方法。
实施例32：中间体38及中间体43的制备。
向配备有磁力搅拌子的20ml微波反应管中依次加入0.5mmol中间体37或者中间体42，1.1mmol对甲苯磺酰肼，6ml正丁醇，将微波管密闭放置微波合成仪中120℃反应5min，反应结束后，，减压除去溶剂，经柱色谱分离得到中间体38或中间体43。
实施例33：中间体39及中间体44的制备。
向配备有磁力搅拌子的20ml微波反应管中依次加入1mmol中间体38或者中间体43，之后迅速加入15.0g吡啶盐酸盐并迅速盖紧微波管，将微波管置于微波合成仪中，保持200℃反应5h，反应结束后将反应物溶解至30ml去离子水，并用乙酸乙酯萃取(20ml×4)，合并萃取液，旋转蒸发脱除溶剂后经柱色谱分离得到中间体39或中间体44。
实施例34：中间体45及中间体47的制备。
以中间体39与中间体25在碱性条件下进行反应得到中间体45及中间体47，具体实施步骤同上述中间体29的制备方法。
实施例35：中间体49及中间体51的制备。
以中间体44与中间体25在碱性条件下进行反应得到中间体49及中间体51，具体实施步骤同上述中间体29的制备方法。
实施例36：目标产物46，48，50，52的制备。
分别以中间体45，47，49，51为原料反应而得。当r基团为叔丁氧羰基时，具体实施步骤同上述中间体11的制备方法。
按照上述实施例1～36所示方法，采用不同的起始原料制备如下化合物，核磁共振氢谱(1hnmr)、碳谱(13cnmr)、高分辨质谱(hrms)表征数据如下:
1hnmr(400mhz,cd3od)δ7.91(d,j＝7.1hz,2h),7.67(s,1h),7.41(t,j＝7.5hz,2h),7.36–7.26(m,1h),3.69(s,2h),3.59–3.51(m,1h),2.59(s,3h),2.24(t,j＝12.1hz,4h),2.17–2.05(m,2h),1.97(d,j＝8.6hz,2h).13cnmr(101mhz,cd3od)δ174.75,156.15,135.85,129.90,129.26,127.47,113.90,64.00,39.82,37.96,33.43,25.94.hrms(ei-tof)calcdforc17h20n2s[m+]m/z284.1347；found,284.1346.
1hnmr(400mhz,cd3od)δ7.85(d,j＝7.8hz,2h),7.47(s,1h),7.29(d,j＝7.9hz,2h),3.71(s,2h),3.57–3.48(m,1h),2.57(s,3h),2.31(s,3h),2.22–2.03(m,6h),1.94(d,j＝8.7hz,2h).13cnmr(101mhz,cd3od)δ173.91,157.23,134.91,131.30,129.46,127.59,114.20,63.80,38.77,38.71,34.50,25.92,21.38.hrms(ei-tof)calcdforc18h22n2s[m+]m/z298.1504；found,298.1502.
1hnmr(400mhz,cd3od)δ7.71(d,j＝8.8hz,2h),7.39(s,1h),6.85(d,j＝8.8hz,2h),3.71(s,3h),3.58–3.38(m,3h),2.45(s,3h),2.23–1.97(m,6h),1.87(d,j＝8.5hz,2h).13cnmr(101mhz,cd3od)δ175.06,161.20,156.16,128.71,115.11,111.74,63.71,55.81,39.85,38.30,33.62,26.06.hrms(ei-tof)calcdforc18h22n2os[m+]m/z314.1453；found,314.1455.
1hnmr(400mhz,cd3od)δ7.96–7.88(m,2h),7.63(s,1h),7.13(t,j＝8.7hz,2h),3.67(s,2h),3.62–3.52(m,1h),2.58(s,3h),2.33–2.08(m,6h),1.99(d,j＝8.1hz,2h).13cnmr(101mhz,cd3od)δ175.05,164.06(d,j＝246.0hz),155.15,132.35,129.34(d,j＝8.2hz),116.50(d,j＝21.9hz),113.48,63.85,39.81,38.09,33.52,25.99.hrms(ei-tof)calcdforc17h19fn2s[m+]m/z302.1253；found,302.1252.
1hnmr(400mhz,cd3od)δ7.89(d,j＝8.6hz,2h),7.71(s,1h),7.39(d,j＝8.6hz,2h),3.78(s,2h),3.67–3.55(m,1h),2.66(s,3h),2.37–2.14(m,6h),2.05(d,j＝8.1hz,2h).13cnmr(101mhz,cd3od)δ174.66,154.95,134.83,134.55,129.90,128.88,114.39,64.18,39.67,37.85,33.29,25.80.hrms(ei-tof)calcdforc17h1935cln2s[m+]m/z318.0957；found,318.0959；calcdforc17h1937cln2s[m+]m/z320.0928；found,320.0927.
1hnmr(400mhz,cd3od)δ7.82(d,j＝8.6hz,2h),7.72(s,1h),7.54(d,j＝8.6hz,2h),3.73(s,2h),3.67–3.51(m,1h),2.62(s,3h),2.36–2.11(m,6h),2.02(d,j＝8.7hz,2h).13cnmr(101mhz,cd3od)δ174.94,154.95,134.95,132.91,129.15,122.90,114.45,64.00,39.76,37.99,33.42,25.91.hrms(ei-tof)calcdforc17h1979brn2s[m+]m/z362.0452；found,362.0449；calcdforc17h1981brn2s[m+]m/z364.0432；found,364.0428.
1hnmr(400mhz,cd3od)δ8.27(d,j＝9.0hz,2h),8.10(d,j＝9.0hz,2h),7.84(s,1h),3.80(s,2h),3.70–3.55(m,1h),2.68(s,3h),2.43–2.35(m,4h),2.22(d,j＝16.6hz,2h),2.08(d,j＝8.8hz,2h).13cnmr(101mhz,cd3od)δ175.21,153.91,148.52,141.73,128.27,125.39,117.71,64.02,40.21,37.90,33.68,26.31.hrms(ei-tof)calcdforc17h19n3o2s[m+]m/z329.1198；found,329.1197.
1hnmr(400mhz,cd3od)δ8.11(d,j＝8.2hz,2h),7.92(s,1h),7.69(d,j＝8.4hz,2h),3.91(s,2h),3.71–3.63(m,1h),2.76(s,3h),2.44–2.35(m,4h),2.23(d,j＝10.1,2h),2.12(d,j＝8.8hz,2h).13cnmr(101mhz,cd3od)δ174.38,154.42,139.32,130.62(q,j＝32.3hz),127.86,126.76(q,j＝3.8hz),125.78(q,j＝271.3hz),116.45,64.52,39.66,37.49,33.09,25.68.hrms(ei-tof)calcdforc18h19f3n2s[m+]m/z352.1221；found,352.1224.
1hnmr(400mhz,cd3od)δ7.94(s,1h),7.73–7.54(m,2h),7.39(d,j＝8.4hz,1h),3.71(s,2h),3.54–3.47(m,1h),2.58(s,3h),2.34–2.06(m,6h),1.98(d,j＝8.5hz,2h).13cnmr(101mhz,cd3od)δ174.64,153.74,135.93,133.93,132.89,131.94,129.37,126.83,115.43,64.18,39.83,37.78,33.37,25.97.hrms(ei-tof)calcdforc17h1835cl2n2s[m+]m/z352.0568；found,352.0562；calcdforc17h1835cl37cln2s[m+]m/z354.0538；found,354.0543；calcdforc17h1837cl2n2s[m+]m/z356.0509；found,356.0518.
1hnmr(400mhz,cd3od)δ7.78–7.74(m,3h),7.23(t,j＝1.9hz,1h),3.74(s,2h),3.58–3.48(m,1h),2.60(s,3h),2.27–2.16(m,4h),2.14–2.07(m,2h),1.99(d,j＝8.8hz,2h).13cnmr(101mhz,cd3od)δ174.77,153.05,138.85,136.53,128.53,125.73,116.48,64.30,39.64,37.73,33.19,25.72.hrms(ei-tof)calcdforc17h1835cl2n2s[m+]m/z352.0568；found,352.0563；calcdforc17h1835cl37cln2s[m+]m/z354.0538；found,354.0542；calcdforc17h1837cl2n2s[m+]m/z356.0509；found,356.0523.
1hnmr(400mhz,cd3od)δ7.60(s,1h),7.52(s,1h),6.63(d,j＝3.0hz,1h),6.40(d,j＝3.3hz,1h),3.71(s,2h),3.57–3.48(m,1h),2.55(s,3h),2.30–2.14(m,6h),2.07(d,j＝9.2hz,2h).13cnmr(101mhz,cd3od)δ172.35,149.26,142.01,140.04,114.35,110.86,105.92,64.30,39.13,37.54,33.24,25.74.hrms(ei-tof)calcdforc15h18n2os[m+]m/z274.1140；found,274.1141.
1hnmr(400mhz,cd3od)δ8.68(d,j＝6.3hz,2h),7.89(d,j＝6.3hz,2h),7.73(s,1h),3.72(s,2h),3.67–3.50(m,1h),2.62(s,3h),2.30–2.17(m,4h),2.13–2.06(m,2h),1.98(d,j＝8.4hz,2h).13cnmr(101mhz,cd3od)δ174.83,151.21,146.35,142.18,122.62,116.27,64.86,39.57,37.31,32.89,26.20.hrms(ei-tof)calcdforc16h19n3s[m+]m/z285.1300；found,285.1299.
1hnmr(400mhz,cd3od)δ7.73(s,1h),7.45(d,j＝8.7hz,2h),6.92(d,j＝8.8hz,2h),3.78(s,3h),3.36–3.27(m,3h),2.30(s,3h),2.14–2.11(m,2h),2.00–1.93(m,2h),1.89(ddd,j＝13.3,5.3,2.9hz,2h),1.73(dd,j＝14.1,6.0hz,2h)ppm.13cnmr(101mhz,cd3od)δ175.40,161.35,139.81,137.08,128.91,125.04,115.68,62.48,55.92,40.26,38.74,34.48,26.81ppm.hrms(ei-tof)calcdforc18h22n2os[m+]m/z314.1453,found314.1457.
1hnmr(400mhz,cd3od)δ7.58(s,1h),7.32(d,j＝7.4hz,1h),7.28–7.27(m,2h),7.25–7.20(m,1h),3.50–3.45(m,3h),2.43(s,3h),2.35(s,3h),2.22–2.19(m,2h),2.12–2.00(m,4h),1.86(dd,j＝14.3,5.8hz,2h)ppm.13cnmr(101mhz,cd3od)δ176.40,140.99,138.28,137.46,132.01,131.61,129.87,127.36,62.97,40.10,38.49,34.10,26.52,21.28ppm.hrms(ei-tof)calcdforc18h22n2s[m+]m/z298.1504,found298.1505.
1hnmr(400mhz,cd3od)δ7.74(s,1h),7.42(d,j＝7.3hz,2h),7.25(t,j＝7.5hz,2h),7.18(t,j＝7.3hz,1h),3.27–3.18(m,3h),2.20(s,3h),2.02–1.99(m,2h),1.91–1.85(m,2h),1.80(ddd,j＝13.3,5.1,2.8hz,2h),1.63(dd,j＝14.2,6.1hz,2h)ppm.13cnmr(101mhz,cd3od)δ176.21,139.85,138.31,132.58,130.34,129.46,127.60,62.60,40.25,38.66,34.46,26.74ppm.hrms(ei-tof)calcdforc17h20n2s[m+]m/z284.1347,found284.1348.
1hnmr(400mhz,cd3od)δ7.87(s,1h),7.53–7.50(m,2h),7.38–7.34(m,2h),3.29–3.28(m,3h),2.32(s,3h),2.15–2.13(m,2h),2.02–1.90(m,4h),1.75(dd,j＝14.3,5.9hz,2h)ppm.13cnmr(101mhz,cd3od)δ176.93,138.83,138.46,135.07,131.33,130.38,128.96,62.45,40.32,38.77,34.61,26.82ppm.hrms(ei-tof)calcdforc17h1935cln2s[m+]m/z318.0957,found318.0956.calcdforc17h1937cln2s[m+]m/z320..0928,found320..0928.
1hnmr(400mhz,cdcl3)δ7.78(s,1h),7.63(s,1h),7.41–7.38(m,2h),7.21(t,j＝7.9hz,1h),3.40–3.34(m,3h),2.39(s,3h),2.14–2.09(m,4h),1.96–1.93(m,2h),1.74(dd,j＝13.8,5.4hz,2h)ppm.13cnmr(101mhz,cdcl3)δ175.44,138.02,136.36,133.51,130.72,130.38,129.16,125.06,122.92,61.06,39.70,37.53,33.81,26.02ppm.hrms(ei-tof)calcdforc17h1979brn2s[m+]m/z362.0452,found362.0454.calcdforc17h1981brn2s[m+]m/z364.0432,found364.0436.
1hnmr(400mhz,cdcl3)δ8.18–8.15(m,2h),7.89(s,1h),7.62–7.58(m,2h),3.50(br,s,2h),3.39(tt,j＝11.9,5.4hz,1h),2.48(s,3h),2.35(t,j＝12.4hz,2h),2.20–2.17(m,2h),2.00–1.97(m,2h),1.82(dd,j＝14.9,6.1hz,2h)ppm.13cnmr(101mhz,cdcl3)δ175.07,146.05,138.80,136.88,135.20,125.93,123.46,60.79,38.37,35.88,32.55,24.68ppm.hrms(ei-tof)calcdforc17h19n3o2s[m+]m/z329.1198,found329.1197.
1hnmr(400mhz,cdcl3)δ7.78(s,1h),7.51(br,s,4h),3.50(br,s,2h),3.35(tt,j＝11.9,5.4hz,1h),2.47(s,3h),2.33(t,j＝12.2hz,2h),2.18–2.14(m,2h),1.98–1.92(m,2h),1.79(dd,j＝14.6,6.0hz,2h)ppm.13cnmr(100mhz,cdcl3)δ173.71,137.72,135.95,133.97,128.75(q,j＝32.7hz),125.70,124.98(q,j＝3.7hz),122.97(q,j＝272.1hz),60.86,38.30,35.76,32.37,24.65ppm.hrms(ei-tof)calcdforc18h19f3n2s[m+]m/z352.1221,found352.1222.
1hnmr(400mhz,cd3od)δ7.65(s,1h),7.42–7.38(m,2h),7.03–6.97(m,2h),3.50(br,s,2h),3.35(tt,j＝11.6,5.3hz,1h),2.48(s,3h),2.33(t,j＝12.3hz,2h),2.19–2.14(m,2h),1.98–1.94(m,2h),1.82(dd,j＝14.4,6.1hz,2h)ppm.13cnmr(101mhz,cd3od)δ172.24(s),161.76(d,j＝248.4hz),136.94,136.16,127.49(d,j＝8.2hz),126.43(d,j＝3.4hz),115.15(d,j＝22.0hz),61.15,37.92,35.51,31.80,24.40ppm.hrms(ei-tof)calcdforc17h19fn2s[m+]m/z302.1253,found302.1252.
1hnmr(400mhz,cd3od)δ8.28(s,1h),8.09(dd,j＝8.2,2.0hz,1h),7.85(s,1h),7.76(d,j＝7.8hz,1h),7.51(t,j＝8.0hz,1h),3.68(br,s,2h),3.44(tt,j＝12.0,5.5hz,1h),2.61(s,3h),2.61–2.54(m,2h),2.28–2.25(m,2h),2.07–2.02(m,2h),1.93(dd,j＝14.6,5.8hz,2h)ppm.13cnmr(100mhz,cd3od)δ175.00,150.05,140.35,137.96,134.20,133.79,131.76,124.16,122.36,64.27,39.81,37.31,33.57,26.07ppm.hrms(ei-tof)calcdforc17h19n3o2s[m+]m/z329.1198,found329.1197.
1hnmr(400mhz,cd3od)δ7.75(s,1h),7.43–7.37(m,2h),7.26–7.22(m,2h),3.79(br,s,2h),3.48(tt,j＝12.0,5.5hz,1h),2.66(s,3h),2.44–2.37(m,2h),2.32–2.28(m,2h),2.15–2.10(m,2h),2.01(dd,j＝14.8,5.8hz,2h)ppm.13cnmr(101mhz,cd3od)δ174.63,142.50,136.26,133.82,132.76,131.86,131.16,130.98,128.65,64.21,39.78,37.11,33.34,26.21ppm.hrms(ei-tof)calcdforc17h1935cln2s[m+]m/z318.0957,found318.0956.calcdforc17h1937cln2s[m+]m/z320.0928,found320.0930.
1hnmr(400mhz,cdcl3)δ7.87(d,j＝1.3hz,1h),7.32(t,j＝8.1hz,1h),7.28–7.22(m,2h),3.35–3.28(m,3h),2.32(s,3h),2.09–2.01(m,4h),1.91–1.86(m,2h),1.68(dd,j＝14.4,6.2hz,2h)ppm.13cnmr(101mhz,cdcl3)δ175.08,157.49(d,j＝254.7hz),139.57(d,j＝7.4hz),129.03(d,j＝4.5hz),128.90(d,j＝4.0hz),126.93(d,j＝3.5hz),120.52(d,j＝9.6hz),118.89(d,j＝25.5hz),117.87(d,j＝13.8hz),60.13,38.77,36.67,32.80,25.10ppm.hrms(ei-tof)calcdforc17h1879brfn2s[m+]m/z380.0358,found380.0359.calcdforc17h1881brfn2s[m+]m/z382.0338,found382.0338.
1hnmr(400mhz,cdcl3)δ7.75(s,1h),7.40(d,j＝8.1hz,2h),7.18(d,j＝7.9hz,2h),3.40–3.32(m,3h),2.39(s,3h),2.36(s,3h),2.15–2.08(m,4h),1.95(ddd,j＝13.5,5.2,3.3hz,2h),1.75(dd,j＝14.4,6.2hz,2h)ppm.13cnmr(101mhz,cdcl3)δ174.34,138.35,137.96,136.85,129.65,128.75,126.50,61.20,39.75,37.70,33.87,26.13,21.18ppm.hrms(ei-tof)calcdforc18h22n2s[m+]m/z298.1504,found298.1505.
1hnmr(400mhz,cdcl3)δ7.69(s,1h),7.06(s,2h),6.87(s,1h),3.33–3.25(m,3h),2.31(s,3h),2.26(s,3h),2.08–1.98(m,4h),1.87(ddd,j＝13.0,4.6,2.6hz,2h),1.67(dd,j＝14.4,6.3hz,2h)ppm.13cnmr(101mhz,cdcl3)δ173.59,137.56,137.44,136.12,130.37,128.73,123.47,60.06,38.67,36.65,32.87,25.15,20.23ppm.hrms(ei-tof)calcdforc19h24n2s[m+]m/z312.1660,found312.1663.
1hnmr(400mhz,cdcl3)δ7.72(s,1h),7.45–7.42(m,2h),7.33–7.30(m,2h),3.73(br,s,2h),3.42(tt,j＝10.0,5.4hz,1h),2.68–2.62(m,5h),2.30–2.27(m,2h),2.07–2.02(m,2h),1.96(dd,j＝14.8,5.9hz,2h)ppm.13cnmr(101mhz,cdcl3)δ174.29,136.71,136.03,131.11,129.56,127.01,120.89,60.17,38.76,36.69,32.91,25.08ppm.hrms(ei-tof)calcdforc17h1979brn2s[m+]m/z362.0452,found362.0451.calcdforc17h1981brn2s[m+]m/z364.0432,found364.0434.
1hnmr(400mhz,cdcl3)δ7.83(s,1h),7.59(d,j＝8.4hz,2h),7.53(d,j＝8.4hz,2h),3.36–3.30(m,3h),2.33(s,3h),2.10–2.04(m,4h),1.92–1.87(m,2h),1.69(dd,j＝14.0,5.8hz,2h)ppm.13cnmr(101mhz,cdcl3)δ175.89,138.28,135.18,135.08,131.79,125.81,117.51,110.23,60.20,38.92,36.81,33.02,25.04ppm.hrms(ei-tof)calcdforc18h19n3s[m+]m/z309.1300,found309.1299.
1hnmr(400mhz,cdcl3)δ7.77(s,1h),7.54–7.51(m,2h),7.23(d,j＝8.1hz,2h),3.40–3.33(m,1h),3.31–3.29(m,2h),2.36(s,3h),2.14–2.11(m,2h),2.05(td,j＝13.1,2.3hz,2h),1.94(ddd,j＝13.3,5.1,3.0hz,2h),1.72(dd,j＝14.4,6.3hz,2h)ppm.13cnmr(101mhz,cdcl3)δ175.82,148.72,137.83,136.52,130.43,127.87,121.45,120.38(q,j＝257.6hz).61.04,39.94,37.98,34.02,26.13ppm.hrms(ei-tof)calcdforc18h19f3n2os[m+]m/z368.1170,found368.1173.
1hnmr(400mhz,cdcl3)δ7.71(s,1h),7.26–7.22(m,2h),7.18(t,j＝7.4hz,1h),7.04(d,j＝7.1hz,1h),3.54(br,s,2h),3.37(tt,j＝11.4,5.0hz,1h),2.53(s,3h),2.40(t,j＝12.8hz,2h),2.30(s,3h),2.21–2.18(m,2h),1.99–1.96(m,2h),1.87–1.82(m,2h)ppm.13cnmr(101mhz,cdcl3)δ171.73,137.99,137.74,136.25,130.25,127.96,127.90,126.39,122.77,60.90,37.87,35.35,32.15,24.63,20.35ppm.hrms(ei-tof)calcdforc18h22n2s[m+]m/z298.1504,found298.1503.
1hnmr(400mhz,cdcl3)δ7.72(s,1h),7.21(t,j＝7.9hz,1h),7.03(d,j＝7.5hz,1h),6.97(s,1h),6.78(d,j＝8.2hz,1h),3.76(s,3h),3.50(br,s,2h),3.35(tt,j＝11.5,5.3hz,1h),2.49(s,3h),2.33(t,j＝12.6hz,2h),2.19–2.16(m,2h),1.98–1.95(m,2h),1.84–1.79(m,2h)ppm.13cnmr(101mhz,cdcl3)δ172.29,158.94,137.54,136.56,131.65,129.05,118.19,112.61,111.29,60.67,54.34,37.94,35.52,32.26,24.72ppm.hrms(ei-tof)calcdforc18h22n2os[m+]m/z314.1453,found314.1456.
1hnmr(400mhz,cdcl3)δ7.75(s,1h),7.33(s,1h),7.32(s,1h),7.22(t,j＝1.8hz,1h),3.49(br,s,2h),3.41–3.32(m,1h),2.48(s,3h),2.34(t,j＝12.8hz,2h),2.20–2.17(m,2h),1.99–1.94(m,2h),1.82(dd,j＝14.3,5.8hz,2h)ppm.13cnmr(101mhz,cdcl3)δ176.11,138.80,135.55,135.43,134.44,127.77,124.83,61.27,39.72,37.51,33.91,26.03ppm.hrms(ei-tof)calcdforc17h1835cl2n2s[m+]m/z352.0568,found352.0567.calcdforc17h1835cl37cln2s[m+]m/z354.0538,found354.0544.calcdforc17h1837cl2n2s[m+]m/z356.0509,found356.0518.
1hnmr(400mhz,cdcl3)δ7.73(s,1h),7.30–7.20(m,2h),7.14(dt,j＝9.8,2.2hz,1h),6.95–6.90(m,1h),3.58(br,s,2h),3.38(tt,j＝12.0,5.5hz,1h),2.55(s,3h),2.44(t,j＝12.4hz,2h),2.24–2.20(m,2h),2.02–1.97(m,2h),1.87(dd,j＝14.6,5.9hz,2h)ppm.13cnmr(101mhz,cdcl3)δ172.46,161.96(d,j＝246.7hz),137.07,136.53(d,j＝2.7hz),132.41(d,j＝8.3hz),129.61(d,j＝8.6hz),121.42(d,j＝2.9hz),113.96(d,j＝21.2hz),112.44(d,j＝23.0hz),60.98,37.93,35.32,32.14,24.57ppm.hrms(ei-tof)calcdforc17h19fn2s[m+]m/z302.1253,found302.1254.
1hnmr(400mhz,cdcl3)δ7.73(s,1h),7.42(t,j＝1.6hz,1h),7.31(dt,j＝7.3,1.6hz,1h),7.23(t,j＝7.7hz,1h),7.19(dt,j＝7.9,1.7hz,1h),3.53(br,s,2h),3.36(tt,j＝12.0,5.4hz,1h),2.51(s,3h),2.38(t,j＝12.3hz,2h),2.21–2.17(m,2h),1.99–1.94(m,2h),1.83(dd,j＝14.6,6.0hz,2h)ppm.13cnmr(101mhz,cdcl3)δ172.86,137.09,136.19,133.87,132.13,129.25,127.06,125.48,123.81,60.86,38.08,35.53,32.27,24.65ppm.hrms(ei-tof)calcdforc17h1935cln2s[m+]m/z318.0957,found318.0961.calcdforc17h1937cln2s[m+]m/z320.0928,found320.0932.
1hnmr(400mhz,cdcl3)δ7.78(s,1h),7.66(s,1h),7.61(d,j＝7.6hz,1h),7.49–7.41(m,2h),3.67(br,s,2h),3.42(tt,j＝11.8,5.3hz,1h),2.61–2.52(m,5h),2.27–2.24(m,2h),2.05–2.00(m,2h),1.91(dd,j＝14.5,5.9hz,2h)ppm.13cnmr(101mhz,cdcl3)δ172.37,137.39,136.35,131.20,130.44(q,j＝32.5hz),128.91,128.62,123.71(q,j＝3.6hz),122.78(q,j＝272.5hz),122.22(q,j＝3.7hz),61.22,37.78,35.01,31.98,24.42ppm.hrms(ei-tof)calcdforc18h19f3n2s[m+]m/z352.1221,found352.1223.
1hnmr(400mhz,cdcl3)δ7.69(s,1h),7.59(dd,j＝8.0,1.1hz,1h),7.36(dd,j＝7.7,1.7hz,1h),7.26(td,j＝7.6,1.2hz,1h),7.13(td,j＝7.7,1.7hz,1h),3.58(br,s,2h),3.40(tt,j＝12.0,5.5hz,1h),2.55(s,3h),2.44(t,j＝12.3hz,2h),2.24–2.21(m,2h),2.05–1.99(m,2h),1.87(dd,j＝14.7,6.0hz,2h)ppm.13cnmr(101mhz,cdcl3)δ173.06,140.40,134.89,132.65,131.14,130.98,128.70,126.57,122.02,60.86,37.73,35.13,31.94,24.64ppm.hrms(ei-tof)calcdforc17h1979brn2s[m+]m/z362.0452,found362.0453.calcdforc17h1981brn2s[m+]m/z364.0432,found364.0432.
1hnmr(400mhz,cdcl3)δ7.92(s,1h),7.48(d,j＝7.4hz,1h),7.21(t,j＝7.6hz,1h),6.91(t,j＝8.9hz,2h),3.84(s,3h),3.54(br,s,2h),3.38(tt,j＝11.2,5.1hz,1h),2.53(s,3h),2.39(t,j＝11.8hz,2h),2.22–2.20(m,2h),2.01–1.96(m,2h),1.87–1.82(m,2h)ppm.13cnmr(101mhz,cdcl3)δ173.17,155.35,139.61,133.57,129.12,128.57,120.98,120.41,111.42,61.76,55.54,38.65,36.19,32.89,25.71ppm.hrms(ei-tof)calcdforc18h22n2os[m+]m/z314.1453,found314.1452.
1hnmr(400mhz,cdcl3)δ8.02–8.00(m,1h),7.81–7.77(m,2h),7.65(s,1h),7.44–7.37(m,4h),3.46(br,s,2h),3.43–3.35(m,1h),2.45(s,3h),2.36–2.29(m,2h),2.17–2.13(m,2h),1.99(ddd,j＝13.4,4.6,2.7hz,2h),1.79(dd,j＝14.5,6.0hz,2h)ppm.13cnmr(101mhz,cdcl3)δ173.50,139.85,134.49,132.70,130.80,128.06,127.68,127.63,127.40,125.74,125.18,124.20,124.19,60.61,38.11,35.78,32.29,24.81ppm.hrms(ei-tof)calcdforc21h22n2s[m+]m/z334.1504,found334.1506.
1hnmr(400mhz,cdcl3)δ8.54(d,j＝2.2hz,1h),7.84(s,1h),7.77(dd,j＝8.3,2.5hz,1h),7.36(d,j＝8.3hz,1h),3.44–3.36(m,3h),2.40(s,3h),2.17–2.10(m,4h),2.00–1.94(m,2h),1.77(dd,j＝14.0,5.9hz,2h)ppm.13cnmr(101mhz,cdcl3)δ176.51,150.60,147.02,138.84,136.31,132.99,126.87,124.45,61.20,39.86,37.75,33.96,26.04ppm.hrms(ei-tof)calcdforc16h1835cln3s[m+]m/z319.0910,found319.0912.calcdforc16h1837cln3s[m+]m/z321.0880,found321.0881.
1hnmr(400mhz,cdcl3)δ7.77(s,1h),7.38(s,1h),7.34(d,j＝8.3hz,1h),7.30–7.27(m,1h),3.99(br,s,2h),3.57(tt,j＝12.1,5.3hz,1h),2.96–2.89(m,2h),2.85(s,3h),2.45–2.42(m,2h),2.40(s,3h),2.21–2.11(m,4h)ppm.13cnmr(101mhz,cdcl3)δ170.76,138.55,137.62,136.87,134.42,129.64,129.59,129.12,125.26,63.02,34.52,32.38,29.68,25.11,20.02ppm.hrms(ei-tof)calcdforc18h2135cln2s[m+]m/z332.1114,found332.1112.calcdforc18h2137cln2s[m+]m/z334.1084,found334.1092.
1hnmr(400mhz,cdcl3)δ7.70(s,1h),7.33–7.26(m,2h),7.00(t,j＝8.9hz,1h),3.40–3.31(m,3h),2.37(s,3h),2.30(s,3h),2.15–2.04(m,4h),1.94(ddd,j＝13.4,5.1,3.2hz,2h),1.74(dd,j＝14.4,6.3hz,2h)ppm.13cnmr(101mhz,cdcl3)δ174.9,161.1(d,j＝246.8hz),137.3,137.1(d,j＝0.9hz),129.7(d,j＝5.3hz),127.5(d,j＝3.8hz),125.6(d,j＝8.1hz),125.5(d,j＝17.8hz)115.6(d,j＝22.9hz),61.1,39.9,37.9,33.9,26.1,14.5(d,j＝3.4hz)ppm.hrms(ei-tof)calcdforc18h21fn2s[m+]m/z316.1409,found316.1408.
1hnmr(400mhz,cdcl3)δ7.77(s,1h),7.50(d,j＝8.3hz,1h),7.36(d,j＝1.9hz,1h),7.18(dd,j＝8.2,2.1hz,1h),3.40–3.32(m,3h),2.41(s,3h),2.38(s,3h),2.15–2.06(m,4h),1.94(ddd,j＝12.9,4.6,2.7hz,2h),1.74(dd,j＝14.4,6.3hz,2h)ppm.13cnmr(101mhz,cdcl3)δ175.20,138.55,137.57,137.11,132.84,130.78,128.70,125.32,124.39,61.15,39.85,37.78,33.95,26.12,22.91ppm.hrms(ei-tof)calcdforc18h2179brn2s[m+]m/z376.0609,found376.0611.calcdforc18h2181brn2s[m+]m/z378.0588,found378.0590.
1hnmr(400mhz,cdcl3)δ7.72(s,1h),7.28–7.27(m,1h),7.22–7.20(m,2h),7.08(d,j＝7.4hz,1h),3.54(br,s,2h),3.37(tt,j＝12.0,5.4hz,1h),2.60(q,j＝7.6hz,2h),2.52(s,3h),2.38(t,j＝13.4hz,2h),2.21–2.18(m,2h),2.01–1.96(m,2h),1.85(dd,j＝14.6,5.9hz,2h),1.19(t,j＝7.6hz,3h)ppm.13cnmr(101mhz,cdcl3)δ171.81,144.12,138.05,136.23,130.29,127.98,126.78,125.29,123.03,60.81,37.89,35.45,32.19,27.77,24.65,14.55ppm.hrms(ei-tof)calcdforc19h24n2s[m+]m/z312.1660,found312.1661.
1hnmr(400mhz,cdcl3)δ7.72(s,1h),7.29–7.28(m,1h),7.26–7.25(m,1h),7.20(s,1h),7.13–7.10(m,1h),3.49(br,s,2h),3.36(tt,j＝11.9,5.3hz,1h),2.86(hept,j＝6.9hz,1h),2.48(s,3h),2.33–2.27(m,2h),2.19–2.15(m,2h),1.99–1.93(m,2h),1.81(dd,j＝14.6,6.0hz,2h),1.20(d,j＝6.9hz,6h)ppm.13cnmr(101mhz,cdcl3)δ172.15,148.75,138.01,136.23,130.31,127.99,125.28,123.95,123.21,60.66,38.07,35.68,33.08,32.30,24.74,22.90ppm.hrms(ei-tof)calcdforc20h26n2s[m+]m/z326.1817,found326.1819.
1hnmr(400mhz,cdcl3)δ7.75(s,1h),7.45(d,j＝8.4hz,2h),7.39(d,j＝8.4hz,2h),3.39–3.28(m,3h),2.36(s,3h),2.13–2.08(m,2h),2.06–2.02(m,2h),1.93(ddd,j＝13.2,4.9,2.9hz,2h),1.72(dd,j＝14.3,6.2hz,2h),1.33(s,9h)ppm.13cnmr(101mhz,cdcl3)δ174.8,151.2,138.1,137.0,128.8,126.4,125.9,61.1,39.9,37.9,34.6,34.0,31.2,26.2ppm.hrms(ei-tof)calcdforc21h28n2s[m+]m/z340.1973,found340.1974.
1hnmr(400mhz,cdcl3)δ7.79(s,1h),7.70(dt,j＝8.9,1.8hz,2h),7.25(dt,j＝8.7,2.1hz,2h),3.40–3.33(m,3h),2.38(s,3h),2.16–2.06(m,4h),1.94(ddd,j＝12.9,4.7,2.9hz,2h),1.75(dd,j＝14.2,6.4hz,2h)ppm.13cnmr(101mhz,cdcl3)δ175.5,138.1,137.8,137.1,131.2,128.2,93.3,61.1,39.8,37.7,34.0,26.1ppm.hrms(ei-tof)calcdforc17h19in2s[m+]m/z410.0314,found410.0316.
1hnmr(400mhz,cdcl3)δ7.74(s,1h),7.56(d,j＝1.6hz,1h),7.46(d,j＝8.6hz,1h),7.21(dd,j＝8.6,1.1hz,1h),3.39(tt,j＝11.9,5.7hz,1h),3.31(br,s,2h),2.36(s,3h),2.15–2.10(m,2h),2.08–2.04(m,2h),1.97(ddd,j＝13.1,5.0,3.0hz,2h),1.73(dd,j＝14.4,6.1hz,2h)ppm.13cnmr(101mhz,cdcl3)δ177.0,148.8(q,j＝2.0hz),141.7,133.9,132.6,131.4,126.0,123.4,120.3(q,j＝258.9hz),119.9,61.1,40.0,38.0,33.9,26.2ppm.hrms(ei-tof)calcdforc18h1879brf3n2os[m+]m/z446.0275,found446.0276.calcdforc18h1881brf3n2os[m+]m/z448.0255,found448.0254.
1hnmr(400mhz,cdcl3)δ7.79(s,1h),7.78(s,1h),7.46(dd,j＝8.5,2.0hz,1h),7.31(d,j＝8.4hz,1h),3.41–3.32(m,3h),2.37(s,3h),2.16–2.04(m,4h),1.97–1.92(m,2h),1.73(dd,j＝14.1,6.2hz,2h)ppm.13cnmr(101mhz,cdcl3)δ176.5,145.9(q,j＝1.5hz),138.6,135.1,132.0,131.7,126.7,122.6,120.4(q,j＝259.6hz),116.7,61.1,39.9,37.9,34.1,26.1ppm.hrms(ei-tof)calcdforc18h1879brf3n2os[m+]m/z446.0275,found446.0273.calcdforc18h1881brf3n2os[m+]m/z448.0255,found448.0258.
1hnmr(400mhz,cdcl3)δ7.76(s,1h),7.20(s,2h),3.38–3.31(m,1h),3.29–3.27(m,2h),2.42(s,6h),2.34(s,3h),2.13–2.09(m,2h),2.03(td,j＝12.9,2.4hz,1h),1.92(ddd,j＝13.2,5.3,3.2hz,2h),1.71(dd,j＝14.3,6.2hz,2h)ppm.13cnmr(101mhz,cdcl3)δ175.3,138.9,137.4,137.1,130.0,126.1,61.0,39.9,37.9,34.0,26.2,23.8ppm.hrms(ei-tof)calcdforc19h2379brn2s[m+]m/z390.0765,found390.0764.calcdforc19h2381brn2s[m+]m/z392.0745,found392.0747.
1hnmr(400mhz,cdcl3)δ7.80(s,1h),7.50(d,j＝8.6hz,1h),7.37(d,j＝1.7hz,2h),7.17(ddd,j＝8.6,2.3,1.0hz,1h),3.39(tt,j＝11.9,5.7hz,1h),3.32–3.30(m,2h),2.37(s,3h),2.15–2.11(m,2h),2.06(dd,j＝12.5,2.0hz,2h),1.96(ddd,j＝13.3,5.4,3.3hz,2h),1.74(dd,j＝14.5,6.2hz,2h)ppm.13cnmr(101mhz,cdcl3)δ177.1,148.8(d,j＝1.8hz),141.7,133.5,132.4,132.2,129.4,122.9,120.3(q,j＝258.8hz),119.5,61.1,39.9,37.9,33.9,26.2ppm.hrms(ei-tof)calcdforc18h1835clf3n2os[m+]m/z402.0780,found402.0782.calcdforc18h1837clf3n2os[m+]m/z404.0751,found404.0751.
1hnmr(400mhz,cdcl3)δ7.84(s,1h),7.62–7.57(m,6h),7.45(t,j＝7.6hz,2h),7.36(t,j＝7.3hz,1h),3.42–3.34(m,1h),3.31–3.30(m,2h),2.37(s,3h),2.14–2.11(m,2h),2.07–2.04(m,2h),1.95(ddd,j＝13.3,5.1,3.1hz,2h),1.73(dd,j＝14.3,6.3hz,2h)ppm.13cnmr(101mhz,cdcl3)δ175.30,140.78,140.28,137.82,137.38,130.62,128.86,127.64,127.56,126.95,126.92,61.09,39.98,38.01,34.08,26.23ppm.hrms(ei-tof)calcdforc23h24n2s[m+]m/z360.1660,found360.1663.
1hnmr(400mhz,cdcl3)δ7.87(s,1h),7.73(s,1h),7.62(d,j＝7.4hz,2h),7.54–7.46(m,5h),7.39(t,j＝7.3hz,1h),3.39(tt,j＝12.0,5.7hz,1h),3.31(br,s,2h),2.38(s,3h),2.16–2.11(m,2h),2.08–2.05(m,2h),1.97(ddd,j＝13.1,4.7,2.8hz,2h),1.74(dd,j＝14.4,6.2hz,3h)ppm.13cnmr(101mhz,cdcl3)δ175.35,142.12,140.57,138.06,137.57,132.14,129.43,128.86,127.65,127.18,126.87,125.50,125.46,61.11,39.94,37.93,34.06,26.23ppm.hrms(ei-tof)calcdforc23h24n2s[m+]m/z360.1660,found360.1662.
1hnmr(400mhz,cdcl3)δ7.86(s,1h),7.73–7.67(m,1h),7.63–7.61(m,1h),7.55–7.37(m,6h),3.43–3.36(m,1h),3.32(br,s,2h),2.39(s,3h),2.16–2.13(m,2h),2.09–2.06(m,2h),2.00–1.94(m,2h),1.75(dd,j＝14.2,6.1hz,2h)ppm.hrms(ei-tof)calcdforc23h2335cln2s[m+]m/z394.1270,found394.1272.calcdforc23h2337cln2s[m+]m/z396.1241,found396.1249.
1hnmr(400mhz,cdcl3)δ7.72(s,1h),7.49–7.45(m,2h),7.38–7.32(m,2h),7.15–7.11(m,1h),7.05–7.04(m,1h),7.03–7.01(m,2h),7.00–6.99(m,1h),3.39–3.32(m,1h),3.29–3.27(m,2h),2.35(s,3h),2.13–2.10(m,2h),2.04(td,j＝12.9,2.3hz,2h),1.93(ddd,j＝13.3,5.3,3.2hz,2h),1.72(dd,j＝14.4,6.3hz,2h)ppm.13cnmr(101mhz,cdcl3)δ174.95,157.31,156.73,138.76,137.56,136.92,129.84,128.06,123.65,119.13,119.09,61.07,40.03,38.08,34.05,26.23ppm.hrms(ei-tof)calcdforc23h24n2os[m+]m/z376.1609,found376.1612.
1hnmr(400mhz,cdcl3)δ7.86(d,j＝3.7hz,1h),7.62(d,j＝5.0hz,1h),7.18(t,j＝4.4hz,1h),4.39–4.30(m,2h),3.39(tt,j＝11.9,5.3hz,1h),2.11–2.05(m,4h),1.93–1.87(m,2h),1.78(dd,j＝14.1,6.5hz,2h),1.49(s,9h)ppm.13cnmr(101mhz,cdcl3)δ173.51,171.07,153.35,131.77,131.65,128.43,125.92,79.40,53.46,52.72,35.08,34.60,28.52,28.29,27.71,27.62ppm.hrms(ei-tof)calcdforc18h23n3o3s[m+]m/z361.1460,found361.1462.
1hnmr(400mhz,cdcl3)δ8.17–8.14(m,2h),7.35(d,j＝8.2hz,2h),4.39–4.32(m,2h),3.47–3.38(m,1h),2.16–2.07(m,4h),1.92–1.88(m,2h),1.83–1.78(m,2h),1.50(s,9h)ppm.13cnmr(101mhz,cdcl3)δ174.20,173.76,153.35,152.23(q,j＝1.6hz),129.90,122.77,121.05,120.26(q,j＝258.9hz),79.37,53.45,52.75,35.01,34.66,28.48,28.27,27.67,27.58ppm.hrms(ei-tof)calcdforc21h24f3n3o4[m+]m/z439.1719,found439.1723.
1hnmr(400mhz,cdcl3)δ8.18(d,j＝8.0hz,2h),7.74(d,j＝8.1hz,2h),4.37–4.28(m,2h),3.41(tt,j＝11.8,5.2hz,1h),2.10–2.04(m,4h),1.90–1.85(m,2h),1.80–1.74(m,2h),1.46(s,9h)ppm.13cnmr(101mhz,cdcl3)δ174.10,173.90,153.36,134.13(q,j＝32.9hz),128.39,127.44(q,j＝1.1hz),126.07(q,j＝3.7hz),123.45(q,j＝272.7hz),79.41,53.43,52.75,34.96,34.63,28.49,28.31,27.70,27.65ppm.hrms(ei-tof)calcdforc21h24f3n3o3[m+]m/z423.1770,found423.1767.
1hnmr(400mhz,cdcl3)δ7.80–7.79(m,1h),7.57–7.56(m,1h),7.13–7.10(m,1h),3.62(br,s,2h),3.23–3.14(m,1h),2.60(s,3h),2.48–2.39(m,2h),2.29–2.26(m,2h),1.97–1.85(m,4h)ppm.13cnmr(101mhz,cdcl3)δ172.48,171.25,131.99,131.85,128.48,125.62,61.27,38.27,32.81,26.32,25.60ppm.hrms(ei-tof)calcdforc14h17n3os[m+]m/z275.1092,found275.1093.
1hnmr(400mhz,cdcl3)δ7.93(s,1h),7.91–7.89(m,1h),7.41–7.36(m,2h),3.31–3.29(m,2h),3.19(tt,j＝12.0,5.5hz,1h),2.42(s,3h),2.37(s,3h),2.19–2.12(m,4h),1.82(ddd,j＝13.6,5.2,3.3hz,2h),1.75–1.69(m,2h)ppm.13cnmr(101mhz,cdcl3)δ175.45,173.97,138.86,133.30,128.88,128.51,125.13,124.26,60.61,39.71,34.63,27.16,26.21,21.24ppm.hrms(ei-tof)calcdforc17h21n3o[m+]m/z283.1685,found283.1683.
1hnmr(400mhz,cdcl3)δ8.17(d,j＝8.8hz,2h),7.36(d,j＝8.2hz,2h),3.41(br,s,2h),3.23(tt,j＝11.8,5.4hz,1h),2.45(s,3h),2.28–2.18(m,4h),1.90–1.84(m,2h),1.79(dd,j＝14.5,6.1hz,2h)ppm.13cnmr(101mhz,cdcl3)δ174.21,173.83,152.23(q,j＝1.7hz),129.95,122.78,121.07,120.27(q,j＝259.0hz),60.84,39.49,34.31,26.88,26.01ppm.hrms(ei-tof)calcdforc17h18f3n3o2[m+]m/z353.1351,found353.1352.
1hnmr(400mhz,cdcl3)δ8.21(d,j＝8.3hz,2h),7.75(d,j＝8.4hz,2h),3.33–3.30(m,2h),3.20(tt,j＝12.0,5.5hz,1h),2.36(s,3h),2.19–2.12(m,4h),1.81(ddd,j＝13.5,5.0,3.1hz,2h),1.72(dd,j＝14.6,6.3hz,2h)ppm.13cnmr(101mhz,cdcl3)δ174.24,173.95,134.00(q,j＝32.9hz),128.37,127.47,126.02(q,j＝3.7hz),123.45(q,j＝272.7hz),60.66,39.78,34.69,27.04,26.08ppm.hrms(ei-tof)calcdforc17h18f3n3o[m+]m/z337.1402,found337.1400.
1hnmr(400mhz,cdcl3)δ8.01(d,j＝8.5hz,2h),7.46(d,j＝8.5hz,2h),3.33(br,s,2h),3.18(tt,j＝11.9,5.5hz,1h),2.38(s,3h),2.20–2.12(m,4h),1.84–1.78(m,2h),1.72(dd,j＝14.3,6.1hz,2h)ppm.13cnmr(101mhz,cdcl3)δ204.82,174.39,173.95,138.93,129.39,129.28,122.78,60.70,39.66,34.52,26.98,26.08ppm.hrms(ei-tof)calcdforc16h1835cln3o[m+]m/z303.1138,found303.1139.calcdforc16h1837cln3o[m+]m/z305.1109,found305.1116.
1hnmr(400mhz,cdcl3)δ8.09(dt,j＝9.5,2.7hz,2h),7.42(d,j＝7.1hz,2h),7.35–7.31(m,4h),7.27–7.25(m,1h),3.62(s,2h),3.41–3.33(m,3h),2.21–2.14(m,4h),1.87(ddd,j＝13.3,5.1,3.4hz,2h),1.74(dd,j＝14.6,6.4hz,2h)ppm.13cnmr(101mhz,cdcl3)δ169.87,163.55,151.38,139.49,128.83,128.57,128.53,128.36,128.26,126.93,122.68,121.25,121.20,120.33(q,j＝258.6hz),58.57,56.51,35.09,27.43,26.42ppm.hrms(ei-tof)calcdforc23h22f3n3o2[m+]m/z429.1664,found429.1666.
1hnmr(400mhz,cdcl3)δ8.20(d,j＝8.1hz,2h),7.87(dd,j＝6.4,2.7hz,2h),7.74(d,j＝8.3hz,2h),7.46–7.40(m,3h),4.20(d,j＝6.4hz,2h),3.93(s,2h),3.66–3.58(m,1h),3.28(t,j＝12.9hz,2h),2.47–2.45(m,2h),2.18–2.10(m,4h)ppm.13cnmr(101mhz,cdcl3)δ167.16,164.14,133.27(q,j＝32.9hz),131.03,130.11,129.40,128.77,127.40,126.29(q,j＝272.9hz),126.73,126.05(q,j＝3.7hz),60.25,55.28,32.60,26.27,24.84ppm.hrms(ei-tof)calcdforc23h22f3n3o[m+]m/z413.1715,found413.1714.
1hnmr(400mhz,cdcl3)δ8.07(d,j＝8.8hz,2h),7.34(d,j＝8.3hz,2h),3.43–3.34(m,3h),2.40(s,3h),2.29–2.17(m,4h),1.90(ddd,j＝13.0,4.4,2.7hz,4h),1.75(dd,j＝14.6,6.3hz,2h)ppm.13cnmr(101mhz,cdcl3)δ169.27,163.67,151.42(q,j＝2.0hz),128.56,122.54,121.19,120.29(q,j＝258.8hz),60.77,40.05,34.59,26.79,25.86ppm.hrms(ei-tof)calcdforc17h18f3n3o2[m+]m/z353.1351,found353.1349.
1hnmr(400mhz,cdcl3)δ7.85(s,1h),7.81(d,j＝7.6hz,1h),7.37(t,j＝7.6hz,1h),7.32(d,j＝7.7hz,1h),3.41–3.32(m,3h),2.42(s,3h),2.37(s,3h),2.23–2.14(m,4h),1.87(ddd,j＝13.5,5.1,3.3hz,2h),1.72(dd,j＝14.5,6.2hz,2h)ppm.13cnmr(101mhz,cdcl3)δ169.05,164.85,138.83,132.30,128.87,127.30,123.88,60.70,40.21,34.83,26.90,25.95,21.28ppm.hrms(ei-tof)calcdforc17h21n3o[m+]m/z283.1685,found283.1684.
1hnmr(400mhz,cdcl3)δ7.90(d,j＝8.9hz,2h),6.94(d,j＝8.9hz,2h),3.82(s,3h),3.34–3.26(m,3h),2.31(s,3h),2.15–2.08(m,4h),1.84–1.79(m,2h),1.66(dd,j＝14.2,6.1hz,2h)ppm.13cnmr(101mhz,cdcl3)δ168.63,164.62,162.14,128.49,116.59,114.39,60.69,55.42,40.14,34.77,26.86,25.97ppm.hrms(ei-tof)calcdforc17h21n3o2[m+]m/z299.1634,found299.1630.
1hnmr(400mhz,cdcl3)δ8.01(d,j＝6.6hz,2h),7.49(d,j＝6.4hz,2h),3.40–3.33(m,3h),2.37(s,3h),2.23–2.14(m,4h),1.90–1.85(m,2h),1.75–1.70(m,2h)ppm.13cnmr(101mhz,cdcl3)δ169.12,164.67,131.49,128.95,126.73,124.01,60.67,40.10,34.68,26.86,25.95ppm.hrms(ei-tof)calcdforc16h18cln3o[m+]m/z,found.
1hnmr(400mhz,cdcl3)δ8.15(d,j＝8.2hz,2h),7.76(d,j＝8.3hz,2h),3.43–3.34(m,3h),2.38(s,3h),2.24–2.16(m,4h),1.90(ddd,j＝12.8,4.6,2.8hz,2h),1.73(dd,j＝14.6,6.3hz,2h)ppm.13cnmr(101mhz,cdcl3)δ169.79,163.57,133.15(q,j＝32.7hz),127.25,127.08,126.04(q,j＝3.8hz),123.55(d,j＝272.7hz),60.71,40.22,34.80,26.92,25.92ppm.hrms(ei-tof)calcdforc17h18f3n3o[m+]m/z337.1402,found337.1403.
1hnmr(400mhz,dmso-d6)δ8.22(d,j＝8.1hz,2h),7.99(d,j＝8.1hz,2h),4.07(br,s,2h),3.80(tt,j＝12.1,6.5hz,1h),3.24(s,3h),3.11(s,3h),2.53–2.50(m,2h),2.43–2.40(m,2h),2.27–2.19(m,4h)ppm.13cnmr(101mhz,dmso-d6)δ168.13,162.98,131.47(q,j＝32.4hz),127.31,127.10,126.41(q,j＝3.6hz),123.67(q,j＝272.4hz),67.54,50.32,43.54,28.69,24.53,22.58ppm.hrms(esi-tof)calcdforc18h21f3n3o[m+]m/z352.1637,found352.1638.
1hnmr(400mhz,cdcl3)δ7.97(d,j＝8.7hz,2h),7.31(d,j＝8.6hz,2h),3.58(tt,j＝11.8,5.6hz,1h),3.36(br,s,2h),2.39(s,3h),2.19–2.12(m,4h),2.04–1.97(m,2h),1.79(dd,j＝14.4,6.0hz,2h)ppm.13cnmr(101mhz,cdcl3)δ175.39,166.65,150.93,129.37,128.88,128.54,121.29,121.20,120.32(q,j＝258.3hz),61.30,40.12,38.51,31.39,25.94ppm.hrms(ei-tof)calcdforc17h18f3n3os[m+]m/z369.1123,found369.1122.
1hnmr(400mhz,cdcl3)δ7.75(s,1h),7.69(d,j＝7.6hz,1h),7.34(t,j＝7.6hz,1h),7.27(d,j＝8.2hz,1h),3.57(tt,j＝11.9,5.6hz,1h),3.35(br,s,2h),2.41(s,3h),2.39(s,3h),2.17–2.10(m,4h),2.02–1.96(m,2h),1.78(dd,j＝14.4,6.3hz,2h)ppm.13cnmr(101mhz,cdcl3)δ174.80,168.42,138.90,131.67,130.16,128.94,128.29,125.06,61.27,40.07,38.46,31.36,25.97,21.29ppm.hrms(ei-tof)calcdforc17h21n3s[m+]m/z299.1456,found299.1457.
1hnmr(400mhz,cdcl3)δ8.16(d,j＝8.2hz,2h),7.76(d,j＝8.3hz,2h),3.50(s,2h),3.48–3.38(m,1h),2.49(s,3h),2.42(t,j＝12.3hz,2h),2.28–2.20(m,2h),2.01–1.93(m,2h),1.83(dd,j＝14.6,6.2hz,2h)ppm.13cnmr(101mhz,cdcl3)δ169.15,163.69,133.19(q,j＝32.9hz),128.12,127.14,126.05(q,j＝3.7hz),123.53(q,j＝272.9hz),61.06,39.74,34.11,26.58,25.66ppm.hrms(ei-tof)calcdforc17h18f3n3s[m+]m/z353.1174,found353.1175.
1hnmr(400mhz,cdcl3)δ7.83(dt,j＝9.6,2.8hz,2h),7.54(d,j＝2.4hz,1h),7.41–7.30(m,5h),7.23(d,j＝8.1hz,2h),6.56(d,j＝2.4hz,1h),5.18(s,2h),4.41–4.37(m,3h),2.62–2.43(m,4h),1.90–1.86(m,2h),1.75–1.73(m,2h)ppm.13cnmr(101mhz,cdcl3)δ153.60,149.06,148.57(q,j＝1.7hz),136.89,132.56,129.46,128.53,128.04,127.92,126.77,121.16,120.52(q,j＝256.7hz),102.91,66.82,52.80,51.99,34.63,33.98,28.46,27.77ppm.hrms(ei-tof)calcdforc25h24f3n3o3[m+]m/z471.1770,found471.1772.
1hnmr(400mhz,cdcl3)δ7.92(d,j＝8.1hz,2h),7.63(d,j＝8.2hz,2h),7.56(d,j＝2.4hz,1h),7.41–7.30(m,5h),6.63(d,j＝2.4hz,1h),5.18(s,2h),4.43–4.38(m,3h),2.62–2.43(m,4h),1.91–1.87(m,2h),1.76–1.71(m,2h)ppm.13cnmr(101mhz,cdcl3)δ153.60,148.89,137.12(q,j＝2.7hz),136.87,129.58,129.27(q,j＝32.4hz),128.54,128.05,127.92,125.55(q,j＝3.9hz),125.54,124.27(q,j＝271.8hz),103.38,66.83,52.93,51.97,34.64,34.01,28.48,27.78ppm.hrms(ei-tof)calcdforc25h24f3n3o2[m+]m/z455.1821,found455.1823.
1hnmr(400mhz,cdcl3)δ7.84(d,j＝8.7hz,2h),7.56(d,j＝2.2hz,1h),7.23(d,j＝8.2hz,2h),6.54(d,j＝2.2hz,1h),4.41(tt,j＝6.5,2.6hz,1h),3.21(br,s,2h),2.56–2.44(m,4h),2.30(s,3h),1.94–1.91(m,2h),1.63(dd,j＝14.2,6.3hz,2h)ppm.13cnmr(101mhz,cdcl3)δ148.87,148.44(q,j＝1.5hz),132.82,129.29,126.72,121.11,120.52(q,j＝256.9hz),102.54,59.53,52.13,40.19,35.16,25.62ppm.hrms(ei-tof)calcdforc18h20f3n3o[m+]m/z351.1558,found351.1559.
1hnmr(400mhz,cdcl3)δ7.65(s,1h),7.61(d,j＝7.7hz,1h),7.54(d,j＝2.3hz,1h),7.27(t,j＝7.6hz,1h),7.09(d,j＝7.5hz,1h),6.54(d,j＝2.3hz,1h),4.40(tt,j＝7.0,2.7hz,1h),3.20–3.17(m,2h),2.58–2.54(m,2h),2.47–2.42(m,2h),2.39(s,3h),2.28(s,3h),1.93–1.89(m,2h),1.65–1.59(m,2h)ppm.13cnmr(101mhz,cdcl3)δ150.27,138.06,133.88,128.89,128.45,128.10,126.10,122.64,102.43,59.54,52.05,40.23,35.13,25.64,21.52ppm.hrms(ei-tof)calcdforc18h23n3[m+]m/z281.1892,found281.1894.
1hnmr(400mhz,cdcl3)δ7.75(d,j＝8.7hz,2h),7.53(d,j＝1.9hz,1h),6.92(d,j＝8.6hz,2h),6.48(d,j＝2.1hz,1h),4.41–4.36(m,1h),3.83(s,3h),3.19(br,s,2h),2.57–2.53(m,2h),2.48–2.41(m,2h),2.29(s,3h),1.93–1.90(m,2h),1.65(dd,j＝14.0,6.3hz,2h)ppm.13cnmr(101mhz,cdcl3)δ159.08,150.00,128.90,126.90,126.67,113.95,101.86,59.56,55.30,51.89,40.20,35.10,25.61ppm.hrms(ei-tof)calcdforc18h23n3o[m+]m/z297.1841,found297.1842.
1hnmr(400mhz,cdcl3)δ7.83(d,j＝7.7hz,2h),7.55(d,j＝1.7hz,1h),7.38(t,j＝7.6hz,2h),6.56(d,j＝2.1hz,1h),4.42–4.39(m,1h),3.21(br,s,2h),2.58–2.54(m,2h),2.50–2.43(m,2h),2.30(s,3h),1.93–1.90(m,2h),1.66(dd,j＝14.1,6.3hz,2h)ppm.13cnmr(101mhz,cdcl3)δ150.13,133.97,129.02,128.54,127.32,125.44,102.46,59.57,51.98,40.16,35.07,25.57ppm.hrms(ei-tof)calcdforc17h2035cln3[m+]m/z301.1346,found301.1343.calcdforc17h2037cln3[m+]m/z303.1316,found303.1317.
1hnmr(400mhz,cdcl3)δ7.93(d,j＝8.2hz,2h),7.63(d,j＝8.2hz,2h),7.59(d,j＝2.1hz,1h),6.62(d,j＝2.2hz,1h),4.45–4.40(m,1h),3.22(br,s,2h),2.57–2.45(m,4h),2.30(s,3h),1.95–1.92(m,2h),1.63(dd,j＝14.2,6.4hz,2h)ppm.13cnmr(101mhz,cdcl3)δ148.71,137.37,129.42,129.08(q,j＝32.3hz),125.49,125.48(q,j＝4.2hz),124.35(q,j＝271.8hz),103.02,59.51,52.27,40.20,35.19,25.62ppm.hrms(ei-tof)calcdforc18h20f3n3[m+]m/z335.1609,found335.1612.
1hnmr(400mhz,cdcl3)δ7.81–7.79(m,2h),7.55(d,j＝2.2hz,1h),7.28–7.25(m,2h),7.02(d,j＝8.6hz,2h),6.96–6.92(m,2h),6.52(d,j＝2.2hz,1h),4.42–4.37(m,1h),3.20(br,s,2h),2.57–2.53(m,2h),2.49–2.42(m,2h),2.29(s,3h),1.94–1.90(m,2h),1.66–1.61(m,2h)ppm.13cnmr(101mhz,cdcl3)δ156.19,156.03,149.50,129.88,129.67,129.15,128.01,127.00,119.76,119.29,102.23,59.56,52.05,40.27,35.17,25.64ppm.hrms(ei-tof)calcdforc23h2435cln3o[m+]m/z393.1608,found393.1610.calcdforc23h2437cln3o[m+]m/z395.1578,found395.1581.
1hnmr(400mhz,cdcl3)δ7.52(d,j＝2.2hz,1h),7.35(d,j＝1.5hz,1h),7.28(dd,j＝8.1,1.6hz,1h),6.83(d,j＝8.1hz,1h),6.45(d,j＝2.3hz,1h),5.96(s,2h),4.37(tt,j＝6.9,2.6hz,1h),3.18(br,s,2h),2.55–2.51(m,2h),2.46–2.39(m,2h),2.28(s,3h),1.93–1.90(m,2h),1.62(dd,j＝14.2,6.2hz,2h)ppm.13cnmr(101mhz,cdcl3)δ149.88,147.86,146.92,128.99,128.45,119.00,108.37,106.17,101.98,100.93,59.50,52.02,40.30,35.20,25.65ppm.hrms(ei-tof)calcdforc18h21n3o2[m+]m/z311.1634,found311.1632.
1hnmr(400mhz,cdcl3)δ7.81–7.78(m,2h),7.55(d,j＝2.3hz,1h),7.35–7.31(m,2h),7.11–7.07(m,1h),7.07–7.01(m,4h),6.51(d,j＝2.3hz,1h),4.40(tt,j＝6.9,2.7hz,1h),3.20(br,s,2h),2.57–2.52(m,2h),2.48–2.42(m,2h),2.29(s,3h),1.94–1.91(m,2h),1.65(dd,j＝14.3,6.3hz,2h)ppm.13cnmr(101mhz,cdcl3)δ157.47,156.44,149.66,129.70,129.47,129.08,126.90,123.06,119.25,118.61,102.18,59.54,52.03,40.26,35.17,26.92,25.63ppm.hrms(ei-tof)calcdforc23h25n3o[m+]m/z359.1998,found359.1999.
1hnmr(400mhz,cdcl3)δ7.87(d,j＝8.7hz,2h),7.56(d,j＝2.2hz,1h),7.30(d,j＝8.7hz,2h),7.25(d,j＝3.8hz,1h),6.81(d,j＝3.8hz,1h),6.54(d,j＝2.3hz,1h),4.40(tt,j＝6.8,2.8hz,1h),3.19(br,s,2h),2.56–2.52(m,2h),2.48–2.41(m,2h),2.29(s,3h),1.94–1.91(m,2h),1.63(dd,j＝14.2,6.3hz,2h)ppm.13cnmr(101mhz,cdcl3)δ174.14,154.73,149.16,137.67,132.00,129.20,126.98,120.35,112.87,102.44,59.49,52.16,40.32,35.26,25.65ppm.hrms(ei-tof)calcdforc20h22n4os[m+]m/z366.1514,found366.1510.
1hnmr(400mhz,cdcl3)δ8.03(d,j＝4.8hz,1h),7.87(d,j＝8.6hz,2h),7.76(d,j＝7.7hz,1h),7.55(d,j＝2.0hz,1h),7.18(d,j＝8.6hz,2h),6.96(dd,j＝7.5,4.9hz,1h),6.55(d,j＝2.2hz,1h),4.44–4.39(m,1h),3.23(br,s,2h),2.60–2.56(m,2h),2.51–2.45(m,2h),2.31(s,3h),1.94–1.91(m,2h),1.67(dd,j＝14.0,6.3hz,2h)ppm.13cnmr(101mhz,cdcl3)δ159.16,152.84,149.53,145.19,139.24,131.13,129.06,126.67,121.57,119.18,119.06,102.45,59.61,51.90,40.13,34.99,25.45ppm.hrms(ei-tof)calcdforc22h2335cln4o[m+]m/z394.1560,found394.1558.calcdforc22h2337cln4o[m+]m/z396.1531,found396.1530.
1hnmr(400mhz,cdcl3)δ7.86(s,1h),7.83(s,1h),7.62–7.57(m,4h),4.42–4.27(m,3h),2.57–2.45(s,4h),1.91–1.84(m,2h),1.69–1.61(m,2h),1.51(s,9h)ppm.13cnmr(101mhz,cdcl3)δ153.53,136.23(q,j＝1.3hz),136.15,128.27(q,j＝32.4hz),125.84(q,j＝3.7hz),125.47,125.44,124.25(q,j＝271.9hz),79.62,53.21,51.88,51.12,34.53,34.13,28.76,28.51,28.27ppm.hrms(ei-tof)calcdforc22h26f3n3o2[m+]m/z421.1977,found421.1976.
1hnmr(400mhz,cdcl3)δ7.79(s,1h),7.76(s,1h),7.49(d,j＝8.8hz,2h),7.21(d,j＝8.0hz,2h),4.41–4.24(m,3h),2.59–2.44(m,4h),1.90–1.87(m,2h),1.67–1.62(m,2h),1.50(s,9h)ppm.13cnmr(101mhz,cdcl3)δ153.52,147.64(q,j＝1.6hz),135.92,131.55,126.67,125.03,121.77,121.50,120.53(q,j＝258.7hz)79.56,53.10,51.97,51.11,34.52,34.07,28.69,28.51,28.15ppm.hrms(ei-tof)calcdforc22h26f3n3o3[m+]m/z437.1926,found437.1928.
1hnmr(400mhz,cdcl3)δ7.72(s,2h),7.41(d,j＝8.8hz,2h),6.91(d,j＝8.7hz,2h),4.39(tt,j＝6.8,3.9hz,1h),3.82(s,3h),3.21(br,s,2h),2.49–2.36(m,4h),2.28(s,3h),1.96–1.92(m,2h),1.58(dd,j＝14.3,6.3hz,2h)ppm.13cnmr(101mhz,cdcl3)δ158.25,135.49,126.63,125.51,124.31,122.45,114.27,59.44,55.33,52.17,40.31,35.36,25.92ppm.hrms(ei-tof)calcdforc18h23n3o[m+]m/z297.1841,found297.1845.
1hnmr(400mhz,cdcl3)δ7.78(s,1h),7.77(s,1h),7.29(d,j＝9.8hz,2h),7.24(t,j＝7.5hz,1h),7.03(d,j＝7.2hz,1h),4.39(tt,j＝6.8,3.6hz,1h),3.20(br,s,2h),2.53–2.41(m,4h),2.37(s,3h),2.28(s,3h),1.95–1.91(m,2h),1.56(dd,j＝14.3,6.4hz,2h)ppm.13cnmr(101mhz,cdcl3)δ138.38,135.80,132.71,128.73,127.06,126.19,124.81,122.75,122.55,59.42,52.25,40.31,35.34,25.92,21.48ppm.hrms(ei-tof)calcdforc18h23n3[m+]m/z281.1892,found281.1895.
1hnmr(400mhz,cdcl3)δ7.77(s,1h),7.75(s,1h),7.40(d,j＝8.4hz,2h),7.31(d,j＝8.3hz,2h),4.40(tt,j＝6.8,3.7hz,1h),3.20(br,s,2h),2.49–2.43(m,4h),2.27(s,3h),1.96–1.93(m,2h),1.55(dd,j＝14.1,6.0hz,2h)ppm.13cnmr(101mhz,cdcl3)δ135.71,131.80,131.35,128.92,126.63,124.90,121.59,59.36,52.42,40.35,35.50,26.03ppm.hrms(ei-tof)calcdforc17h2035cln3[m+]m/z301.1346,found301.1348.calcdforc17h2037cln3[m+]m/z303.1316,found303.1321.
1hnmr(400mhz,cdcl3)δ7.85(s,1h),7.82(s,1h),7.61–7.56(m,4h),4.43(p,j＝5.2hz,1h),3.23–3.21(m,2h),2.49–2.47(m,4h),2.28(s,3h),1.98–1.94(m,2h),1.56(dd,j＝14.9,6.0hz,2h)ppm.13cnmr(101mhz,cdcl3)δ136.43,135.97,128.07(q,j＝32.5hz),125.76(q,j＝3.7hz),125.41,125.36,124.28(q,j＝271.7hz),121.36,59.34,52.54,40.31,35.50,26.02ppm.hrms(ei-tof)calcdforc18h20f3n3[m+]m/z335.1609,found335.1612.
1hnmr(400mhz,cdcl3)δ7.78(s,1h),7.75(s,1h),7.48(d,j＝8.5hz,2h),7.20(d,j＝8.1hz,2h),4.41(p,j＝5.0hz,1h),3.21(br,s,2h),2.49–2.47(m,4h),2.28(s,3h),1.97–1.93(m,2h),1.57(dd,j＝14.5,6.2hz,2h)ppm.13cnmr(101mhz,cdcl3)δ147.55(q,j＝1.7hz),135.76,131.73,126.61,124.99,121.46,120.50(d,j＝256.9hz),59.40,52.36,40.26,35.38,25.92ppm.hrms(ei-tof)calcdforc18h20f3n3o[m+]m/z351.1558,found351.1561.
1hnmr(400mhz,cdcl3)δ8.66(d,j＝8.4hz,1h),8.05(s,1h),7.99(s,1h),7.74(d,j＝8.4hz,1h),7.54(d,j＝8.9hz,1h),7.33(d,j＝8.9hz,1h),4.64(p,j＝5.1hz,1h),4.37–4.29(m,2h),2.70–2.55(m,4h),1.83–1.81(m,2h),1.68–1.62(m,2h),1.52(s,9h)ppm.13cnmr(101mhz,cdcl3)δ153.52,144.43,131.59,128.03(q,j＝32.2hz),127.87,125.45(q,j＝3.9hz),124.62(q,j＝272.1hz),123.11,123.06,122.81,122.25(q,j＝3.2hz),120.04,119.36,79.52,54.27,52.12,51.32,34.81,34.34,28.57,28.46,27.99ppm.hrms(ei-tof)calcdforc24h26f3n3o2[m+]m/z445.1977,found445.1973.
1hnmr(400mhz,cdcl3)δ8.43(s,1h),8.32(d,j＝8.5hz,1h),8.20(s,1h),7.81–7.76(m,2h),7.53(d,j＝9.1hz,1h),4.79(tt,j＝7.7,5.9hz,1h),4.48–4.32(m,2h),2.74–2.63(m,2h),2.36–2.20(m,2h),2.04–1.93(m,4h),1.55(s,9h)ppm.13cnmr(101mhz,cdcl3)δ153.99,137.77,131.55,129.36,128.34,127.75,126.40(q,j＝32.4hz),126.15(q,j＝4.4hz),124.49(q,j＝271.6hz),123.68,123.19(q,j＝4.2,3.7hz),119.47,111.58,79.57,51.78,50.97,49.78,35.68,35.32,29.79,29.31,28.55ppm.hrms(ei-tof)calcdforc24h26f3n3o2[m+]m/z445.1977,found445.1976.
1hnmr(400mhz,cdcl3)δ8.48(s,1h),8.15(d,j＝8.3hz,1h),8.10(s,1h),7.76–7.71(m,2h),7.62(d,j＝9.2hz,1h),4.68(p,j＝5.6hz,1h),4.42–4.33(m,2h),2.75–2.59(m,4h),1.92–1.89(m,2h),1.70–1.63(m,2h),1.52(s,9h)ppm.13cnmr(101mhz,cdcl3)δ153.59,147.12,129.81,129.58,127.56,126.84(q,j＝32.2hz),126.07(q,j＝4.1hz),124.50(q,j＝271.9hz),123.80,122.64(q,j＝3.5hz),122.09,119.31,117.77,79.67,54.50,51.95,51.13,35.16,34.77,29.07,28.52,28.45ppm.hrms(ei-tof)calcdforc24h26f3n3o2[m+]m/z445.1977,found445.1971.
1hnmr(400mhz,cdcl3)δ8.69(d,j＝8.4hz,1h),8.07(s,1h),8.06(s,1h),7.75(dd,j＝8.3,1.2hz,1h),7.59(d,j＝8.9hz,1h),7.37(d,j＝8.9hz,1h),4.71(tt,j＝6.6,3.1hz,1h),3.25(s,2h),2.69–2.57(m,4h),2.30(s,3h),1.94–1.91(m,2h),1.64–1.59(m,2h)ppm.13cnmr(101mhz,cdcl3)δ144.46,131.54,127.96(q,j＝32.2hz),127.90,125.47(q,j＝4.1hz),124.62(q,j＝272.1hz),123.06,122.99,122.73,122.24(q,j＝3.3hz),120.10,119.23,59.49,53.54,40.15,35.73,25.82.hrms(ei-tof)calcdforc20h20f3n3[m+]m/z359.1609,found359.1611.
1hnmr(400mhz,cdcl3)δ8.38(s,1h),8.22(d,j＝8.1hz,1h),7.89(d,j＝8.0hz,1h),7.68(d,j＝9.1hz,1h),7.61–7.57(m,1h),7.50(d,j＝9.1hz,1h),7.47–7.43(m,1h),4.95(tt,j＝8.0,5.7hz,1h),3.30–3.27(m,2h),2.65(dt,j＝14.6,7.6hz,2h),2.31(s,3h),2.22(ddd,j＝14.3,5.6,1.1hz,2h),2.11–2.04(m,2h),1.93–1.88(m,2h)ppm.13cnmr(101mhz,cdcl3)δ137.21,130.92,129.30,128.65,127.50,127.39,127.19,124.36,122.85,119.78,110.58,59.49,48.82,40.61,36.96,27.07ppm.hrms(ei-tof)calcdforc19h21n3[m+]m/z291.1735,found291.1738.
1hnmr(400mhz,cdcl3)δ8.34(s,1h),8.14(d,j＝8.6hz,1h),7.86(d,j＝2.1hz,1h),7.59(d,j＝9.1hz,1h),7.53(dd,j＝8.6,2.0hz,2h),4.94(tt,j＝8.0,5.8hz,1h),3.30–3.27(m,2h),2.64(dt,j＝14.6,7.6hz,2h),2.31(s,3h),2.19(ddd,j＝14.4,5.8,1.2hz,2h),2.10–2.07(m,2h),1.88(dd,j＝13.9,6.3hz,2h)ppm.13cnmr(101mhz,cdcl3)δ137.15,130.85,130.19,129.79,127.67,127.57,126.32,125.76,124.36,119.46,111.73,59.43,48.98,40.65,37.04,27.13ppm.2dnoesynmr(600mhz,cdcl3)showedacrosspeakfromδ2.22,2.65,4.96toδ7.56.hrms(ei-tof)calcdforc19h2035cln3[m+]m/z325.1346,found325.1345.calcdforc19h2037cln3[m+]m/z327.1316,found327.1322.
1hnmr(400mhz,cdcl3)δ8.42(s,1h),8.31(d,j＝8.5hz,1h),8.19(s,1h),7.80–7.75(m,2h),7.60(d,j＝9.1hz,1h),5.01(tt,j＝8.1,5.0hz,1h),3.40–3.37(m,2h),2.80(dt,j＝14.5,7.5hz,2h),2.40(s,3h),2.29–2.24(m,2h),2.13–2.05(m,2h),2.03–1.98(m,2h)ppm.13cnmr(101mhz,cdcl3)δ137.80,131.37,129.34,128.32,127.63,126.31(q,j＝32.3hz),126.12(q,j＝3.8hz),124.49(q,j＝272.1hz),123.65,123.11(q,j＝3.3hz),119.42,111.87,59.80,48.70,40.30,36.51,26.60ppm.hrms(ei-tof)calcdforc20h20f3n3[m+]m/z359.1609,found359.1604.
1hnmr(400mhz,cdcl3)δ8.40(s,1h),8.05(d,j＝7.9hz,1h),7.80(d,j＝7.9hz,1h),7.66(d,j＝9.2hz,1h),7.55(d,j＝9.2hz,1h),7.51(t,j＝7.5hz,1h),7.42(t,j＝7.5hz,1h),4.69(tt,j＝7.0,3.8hz,1h),3.25(br,s,2h),2.67–2.54(m,4h),2.28(s,3h),1.94–1.91(m,2h),1.57(dd,j＝14.5,6.5hz,2h)ppm.13cnmr(101mhz,cdcl3)δ146.75,130.20,128.83,127.69,127.59,126.55,124.85,123.16,121.27,118.17,117.88,59.46,53.51,40.32,35.91,26.15ppm.hrms(ei-tof)calcdforc19h21n3[m+]m/z291.1735,found291.1737.
1hnmr(400mhz,cdcl3)δ8.37(s,1h),7.97(d,j＝8.5hz,1h),7.77(d,j＝2.1hz,1h),7.68(d,j＝9.2hz,1h),7.47–7.44(m,2h),4.70(p,j＝5.6hz,1h),3.38–3.24(m,2h),2.62–2.59(m,4h),2.29(s,3h),1.97–1.94(m,2h),1.58(dd,j＝14.5,6.3hz,2h)ppm.13cnmr(101mhz,cdcl3)δ146.59,131.29,130.24,127.89,126.83,126.57,125.90,124.57,121.33,119.16,117.75,59.44,53.67,40.33,36.05,26.25ppm.2dnoesynmr(600mhz,cdcl3)showedacrosspeakfromδ1.59,2.63,4.71toδ8.39.hrms(ei-tof)calcdforc19h2035cln3[m+]m/z325.1346,found325.1342.calcdforc19h2037cln3[m+]m/z327.1316,found327.1325.
1hnmr(400mhz,cdcl3)δ8.48(s,1h),8.15(d,j＝8.4hz,1h),8.09(s,1h),7.75(d,j＝9.2hz,1h),7.72(dd,j＝8.4,1.3hz,1h),7.60(d,j＝9.2hz,1h),4.75(p,j＝5.6hz,1h),3.29(p,j＝3.7hz,2h),2.63(dd,j＝5.5,4.0hz,4h),2.31(s,3h),1.99–1.96(m,2h),1.62–1.56(m,2h)ppm.13cnmr(101mhz,cdcl3)δ147.08,129.87(q,j＝0.6hz),129.51,127.37,126.69(q,j＝32.2hz),126.04(q,j＝4.2hz),124.53(q,j＝271.8hz),123.78,122.55(q,j＝3.4hz),122.03,119.37,117.61,59.45,53.82,40.33,36.09,26.26ppm.hrms(ei-tof)calcdforc20h20f3n3[m+]m/z359.1609,found359.1611.
实施例37：本发明化合物的杀线虫测试。
本发明所选取的松材线虫(bursaphelenchusxylophilus)及南方根结线虫(meloidogyneincongnita)均购自中科院湖州现代农业中心，用来测试确定本发明化合物的杀线虫活性。
具体测试操作过程：
电子分析天平分别准确称取阳性对照药物及目标化合物，并用二甲基亚砜溶解，再用含0.2％曲拉通的水溶液稀释成为一定浓度的母液，其中有机溶剂在水中的含量要小于1％，母液浓度为测试所需最高浓度的2倍量。实际测试时，分别取适量的母液和含0.2％曲拉通的水溶液稀释至所需浓度备用。将配制好的药液加入到96孔板中，每孔50μl，每个药物两次重复。用连续加样器在药物中加入线虫悬浮液50μl(线虫约50条)，加盖后置于22±1℃的观察室中。设每毫升0.2％曲拉通的水溶液中含有4ul二甲基亚砜作为ck对照组，阿维菌素(5ppm)及氟噻虫砜(5ppm)为阳性对照组，并于24小时、48小时、72小时检查线虫死亡数，计算两次重复试验中线虫的平均死亡率。
校正死亡率＝(处理组死亡率-对照组死亡率)/(1-对照组死亡率)×100％
表140ppm浓度下本发明化合物对两种线虫的致死率(％)
从表1可以看出，部分化合物在40ppm浓度条件下具有优异的杀线虫活性。
在本发明提及的所有文献都在本申请中引用作为参考，就如同每一篇文献被单独引用作为参考那样。此外应理解，在阅读了本发明的上述讲授内容之后，本领域技术人员可以对本发明作各种改动或修改，这些等价形式同样落于本申请所附权利要求书所限定的范围。