CN110526863B - 一种含三氟甲基吡啶的酰基硫脲或酰基脲类衍生物及其应用 - Google Patents

一种含三氟甲基吡啶的酰基硫脲或酰基脲类衍生物及其应用 Download PDF

Info

Publication number
CN110526863B
CN110526863B CN201910810477.9A CN201910810477A CN110526863B CN 110526863 B CN110526863 B CN 110526863B CN 201910810477 A CN201910810477 A CN 201910810477A CN 110526863 B CN110526863 B CN 110526863B
Authority
CN
China
Prior art keywords
dmso
nmr
chloro
stirring
reaction
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Active
Application number
CN201910810477.9A
Other languages
English (en)
Other versions
CN110526863A (zh
Inventor
徐方舟
吴剑
罗德霞
郭声鑫
何凤
张仁凤
陈顺红
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Guizhou University
Original Assignee
Guizhou University
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Guizhou University filed Critical Guizhou University
Priority to CN201910810477.9A priority Critical patent/CN110526863B/zh
Publication of CN110526863A publication Critical patent/CN110526863A/zh
Application granted granted Critical
Publication of CN110526863B publication Critical patent/CN110526863B/zh
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N47/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid
    • A01N47/08—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid the carbon atom having one or more single bonds to nitrogen atoms
    • A01N47/28—Ureas or thioureas containing the groups >N—CO—N< or >N—CS—N<
    • A01N47/34—Ureas or thioureas containing the groups >N—CO—N< or >N—CS—N< containing the groups, e.g. biuret; Thio analogues thereof; Urea-aldehyde condensation products
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D213/81—Amides; Imides

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Agronomy & Crop Science (AREA)
  • Pest Control & Pesticides (AREA)
  • Plant Pathology (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Dentistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Environmental Sciences (AREA)
  • Pyridine Compounds (AREA)

Abstract

本发明公开了一种含三氟甲基吡啶的酰基硫脲和酰基脲类衍生物及其应用。其结构如通式I所示。式中，对R1、R2、R3、X等基团的限定如说明书中所示。通式I所示的化合物具有优异的杀虫活性，可以用来防治可以用来防治棉铃虫、小菜蛾以及褐飞虱等害虫，也可以用来防治TMV以及CMV等植物病毒病。

Description

一种含三氟甲基吡啶的酰基硫脲或酰基脲类衍生物及其应用
技术领域
本发明涉及农用化学品领域，具体来讲，涉及一种含三氟甲基吡啶的酰基硫脲或酰基脲衍生物在制备杀虫剂和抗植物病毒剂中的应用。
背景技术
在绿色新农药的创制中，含氟农药是人们一直研究的热点领域。氟原子具有电子效应、类氢模拟效应、阻碍效应、脂溶性渗透效应的独特的性质，在药物化学、天然产物化学和农药化学及精细化学品等领域的应用越来越广泛(杨吉春，等.农药,2011,4,289-295)。据不完全统计近10年来所开发的农药新品种中含氟化合物高达50％以上，含氟农药已经成为现在农药行业开发与应用的主要方向(杨吉春，等.农药,2011,4,289-295)，可见氟原子在农药中的重要地位。三氟甲基吡啶作为一类重要的含氟的杂环结构，也是当前商品化农药中的常见基团，在已登记的农药中，含三氟甲基吡啶结构的农药如氟啶虫胺腈、氟啶虫酰胺、啶虫丙醚、氟啶嘧磺隆、氟吡酰菌胺等近30个品种均含有三氟甲基吡啶结构。近些年来，含三氟甲基吡啶结构的化合物备受研究者的关注，研究者在其专利(如：WO,2013191113，WO,2014010737，WO,2014021468，WO,2014119699，JP,2015003906，WO,2015072463，WO,2016024587，CN,104650038，WO,2015177063，WO,2016023954等)中陆续公开了含三氟甲基吡啶结构的化合物具有优异的杀虫活性。
酰基硫脲衍生物一直是一类重要的研究对象。它们不仅是合成多种杂环化合物的有机中间体，也是具有优异活性的杀虫剂、抗菌剂、调节植物生长剂、抗病毒剂和抗肿瘤剂，关于酰基硫脲及酰基脲的应用，更多可见于已有报道中【有机化学,1998(05):481-485；有机化学,2004,24(06):686–690，有机化学,2004,24(06):686–690；应用化学,2013,30(12):1429-1433，CN103351360；化学学报,2007(09):834-840；Molecules,2011,16(9):7593-7607；Bioorganic&Medicinal Chemistry Letters,2016,27(10):2234–2237；化学试剂,2006(01):36–38；有机化学，2014,(10)，2140-2145；高等学校化学学报，1997，3，395-398】。
发明内容
本发明的目的在于将三氟甲基吡啶活性亚结构与酰基硫脲和酰基脲结构进行进行拼接，提供一种结构新颖的含三氟甲基吡啶的酰基硫脲或酰基脲衍生物，并证明该类化合物在防治农业害虫方面的应用。
本发明提供的化合物结构通式如I所示：
Figure GDA0003542938740000011
在通式Ⅰ所示的化合物中，R1为卤素、C1-C3烷氧基、C1-C3烷硫基或C1-C3烷基磺酰基；R2为H、甲基、氯、溴或氟，且为单取代或多取代；R3为C1-C3烷基、环烷基、卤代烷基或羟基代烷基；X为氧或硫。
进一步的R1为Cl、甲氧基、乙氧基、甲硫基、乙硫基、甲磺酰基或乙磺酰基；R2为H、3-甲基、5-氯、5-氯-3-甲基、3,5-二氯、3,5-二氟或硝基；R3为甲基、乙基、正丙基、异丙基、环丙基、环己烷、2,2-二氟乙基、2,2,2-三氟乙基或羟基乙基。
进一步的R1为Cl；R2为3-甲基，5-氯，5-氯-3-甲基、3,5-二氯或3,5-二氟；R3为甲基、乙基、正丙基、异丙基、环丙基、环己烷、2,2-二氟乙基或2,2,2-三氟乙基；X为氧或者硫。
更进一步，当X选自O时，优选以下化合物，但并非对本案所述的结构进行限制。
Figure GDA0003542938740000021
Figure GDA0003542938740000031
更进一步，当X选自S时，优选以下化合物，但并非对本案所述的结构进行限制。
Figure GDA0003542938740000032
Figure GDA0003542938740000041
本发明的通式I化合物可按照以下合称路线所示的方法制备进行，当X为O时，所述合成路线如下：
Figure GDA0003542938740000042
(1)向反应器中加入3-取代-5-三氟甲基吡啶酸以及溶剂，滴加几滴DMF的混合液并搅拌，缓慢加入草酰氯和DCM的混合液，滴加完毕后，在室温下搅拌后停止反应，将体系旋干后得中间体2；
(2)向反应器中加入浓氨水加热搅拌，待体系温度达60℃，缓慢滴加中间体2的二氯甲烷的混合液，滴加完毕，继续搅拌待反应完毕后停止反应，反应液用NaOH水溶液及乙酸乙酯萃取两次，旋干得中间体3；
(3)在反应器中加入中间体3与1，2二氯乙烷，室温搅拌，滴加草酰氯和1，2二氯乙烷的混合液，滴加完毕，加热，半小时后停止反应，脱溶，得中间体4待用；
(4)向另一反应器中加入原料4及四氢呋喃室温搅拌，分次加入三光气，TLC跟踪反应待原料基本消失，脱溶，固体用正己烷溶液洗涤多次得中间体5；
(5)在反应器中加入中间体5及乙腈，室温搅拌，逐滴加入R-NH2的乙腈混合液直至固体固体消失后停止滴加，后用柱层析法(石油醚：乙酸乙酯＝5:1)分离得中间体6；
(6)：反应器中加入中间体4及乙腈搅拌，缓慢加入中间体6，TLC跟踪反应至原料基本消失后停止反应，抽滤得白色固体，并用正己烷：乙酸乙酯＝100:1搅拌洗涤后，抽滤，正己烷洗涤得白色固体纯品。
当X为S时，所述合成路线如下：
Figure GDA0003542938740000051
具体的反应过程如下：
(1)向反应器中加入3-取代-5-三氟甲基吡啶酸以及溶剂，滴加几滴DMF的混合液并搅拌，缓慢加入草酰氯和DCM的混合液，滴加完毕后，在室温下搅拌后停止反应，将体系旋干后得中间体2；
(2)向反应器中加入硫氰化钾，乙腈为溶剂，滴加PEG-400，冰盐条件下缓慢滴加中间体2和乙腈的混合液，后撤掉冰浴锅，继续反应半小时，停止反应，抽滤除去硫氰化钾，减压脱去乙腈溶剂，即得到中间体7，待用；
(3)向反应器中加入原料4，四氢呋喃为溶剂，常温搅拌，分次加入三光气，TLC跟踪反应，待原料基本反应完全后停止反应，脱溶，抽滤，正己烷多次洗涤，中间体5；
(4)向反应器中加入中间体5，乙腈为溶剂，室温搅拌，缓慢滴加R-NH2的乙腈混合液，至固体消失后停止滴加，柱层析分离得到中间体6.
(5)向反应器中加入中间体7，乙腈，随后缓慢加入中间体6，反应30min，停止反应，抽滤，用正己烷：乙酸乙酯＝100:1多次洗涤，抽滤，正己烷洗涤得固体产品，烘干，得目标化合物I-2。
本发明所述的含三氟甲基吡啶的硫脲或者酰基脲类衍生物可用作杀虫剂或抗植物病毒剂中。具体来讲，其特征在于，所述的化合物可用于防治小菜蛾、蚜虫、褐飞虱。也用于防治植物病毒病TMV和CMV。
具体实施例
需要说明的是，本发明化合物酰基脲以及酰基硫脲类化合物的合成方法均一致，所不同的是所采用的起始原料仅在有取代基上有所差别。以下通过部分典型的化合物的制备实例来具体地说明本发明的式I化合物的制备方法，这些实施例仅对本发明的制备方法进行说明，而不是对本发明的化合物进行限制。实施例以外的与本案相关的化合物的制备方法，均可参照相关是实施例进行。为了进一步说明，在实施例后列出来更多的化合物的相关理化数据进行了说明。
实施例1：3-氯-N-((2,4-二氯-6-(甲基氨基甲酰基)苯基)氨基甲酰基)-5-(三氟甲基)吡啶酰胺(I-1a)的制备
Figure GDA0003542938740000061
(1)向50ml单口圆底烧瓶中加入1g(1mmol)3-氯-5-三氟甲基吡啶酸以及5ml溶剂，滴加几滴DMF的混合液并搅拌10min，缓慢加入0.675g(1.2mmol)草酰氯和DCM的混合液,滴加完毕后，在室温下搅拌3h后停止反应，将体系旋干后得中间体2；
(2)向50ml三口烧瓶中加入10ml浓氨水加热搅拌，待体系温度达60℃，缓慢滴加0.3g中间体2的二氯甲烷的混合液，滴加完毕，继续搅拌待反应完毕后停止反应，反应液用10％的NaOH水溶液及乙酸乙酯萃取两次，旋干得中间体3；
(3)在50ml单口圆底烧瓶中加入0.24g(1mmol)中间体3与5ml 1，2-二氯乙烷，室温搅拌，滴加0.23g(1.5mmol)草酰氯和2ml 1，2二氯乙烷的混合液，滴加完毕，加热，半小时后停止反应，脱溶，得中间体4待用；
(4)向100ml三口烧瓶中加入5g原料4及四氢呋喃室温搅拌，分次加入8.65g三光气，TLC跟踪反应待原料基本消失，脱溶，固体用正己烷溶液洗涤多次得中间体5；
(5)在50ml单口圆底烧瓶中加入0.5g中间体5及8ml乙腈，室温搅拌，逐滴加入甲胺的乙腈混合液直至固体固体消失后停止滴加，后用柱层析法(石油醚：乙酸乙酯＝5:1)分离得中间体6；
(6)：三口烧瓶中加入0.27g(1.05mmol)中间体4及10ml乙腈搅拌，缓慢加入0.25g中间体6，TLC跟踪反应至原料基本消失后停止反应，抽滤得白色固体，并用正己烷：乙酸乙酯＝100:1搅拌洗涤后，抽滤，正己烷洗涤得淡黄色固体纯品。
实施例2：3-氯-N-((2-(环丙基氨基)-4-甲基苯基)氨基甲酰基)-5-(三氟甲基)吡啶酰胺(I-1c)的制备
Figure GDA0003542938740000062
(1)向50ml单口圆底烧瓶中加入1g(1mmol)3-氯-5-三氟甲基吡啶酸以及5ml溶剂，滴加几滴DMF的混合液并搅拌10min，缓慢加入0.675g(1.2mmol)草酰氯和DCM的混合液,滴加完毕后，在室温下搅拌3h后停止反应，将体系旋干后得中间体2；
(2)向50ml三口烧瓶中加入10ml浓氨水加热搅拌，待体系温度达60℃，缓慢滴加0.3g中间体2的二氯甲烷的混合液，滴加完毕，继续搅拌待反应完毕后停止反应，反应液用10％的NaOH水溶液及乙酸乙酯萃取两次，旋干得中间体3；
(3)在50ml单口圆底烧瓶中加入0.24g(1mmol)中间体3与5ml 1，2-二氯乙烷，室温搅拌，滴加0.23g(1.5mmol)草酰氯和2ml 1，2二氯乙烷的混合液，滴加完毕，加热，半小时后停止反应，脱溶，得中间体4待用；
(4)向100ml三口烧瓶中加入5g原料4及四氢呋喃室温搅拌，分次加入8.65g三光气，TLC跟踪反应待原料基本消失，脱溶，固体用正己烷溶液洗涤多次得中间体5；
(5)在50ml单口圆底烧瓶中加入0.5g中间体5及8ml乙腈，室温搅拌，逐滴加入甲胺的乙腈混合液直至固体固体消失后停止滴加，后用柱层析法(石油醚：乙酸乙酯＝5:1)分离得中间体6；
(6)：三口烧瓶中加入0.35g(1.05mmol)中间体4及10ml乙腈搅拌，缓慢加入0.25g中间体6，TLC跟踪反应至原料基本消失后停止反应，抽滤得白色固体，并用正己烷：乙酸乙酯＝100:1搅拌洗涤后，抽滤，正己烷洗涤得米白色固体纯品。
实施例3：3-氯-N-((2-氯-6-(环己基)苯基)氨基甲酰基)-5-(三氟甲基)吡啶酰胺(I-1i)
Figure GDA0003542938740000071
(1)向50ml单口圆底烧瓶中加入1g(1mmol)3-氯-5-三氟甲基吡啶酸以及5ml溶剂，滴加几滴DMF的混合液并搅拌10min，缓慢加入0.675g(1.2mmol)草酰氯和DCM的混合液,滴加完毕后，在室温下搅拌3h后停止反应，将体系旋干后得中间体2；
(2)向50ml三口烧瓶中加入10ml浓氨水加热搅拌，待体系温度达60℃，缓慢滴加0.3g中间体2的二氯甲烷的混合液，滴加完毕，继续搅拌待反应完毕后停止反应，反应液用10％的NaOH水溶液及乙酸乙酯萃取两次，旋干得中间体3；
(3)在50ml单口圆底烧瓶中加入0.24g(1mmol)中间体3与5ml 1，2-二氯乙烷，室温搅拌，滴加0.23g(1.5mmol)草酰氯和2ml 1，2二氯乙烷的混合液，滴加完毕，加热，半小时后停止反应，脱溶，得中间体4待用；
(4)向100ml三口烧瓶中加入5g原料4及四氢呋喃室温搅拌，分次加入8.65g三光气，TLC跟踪反应待原料基本消失，脱溶，固体用正己烷溶液洗涤多次得中间体5；
(5)在50ml单口圆底烧瓶中加入0.5g中间体5及8ml乙腈，室温搅拌，逐滴加入甲胺的乙腈混合液直至固体固体消失后停止滴加，后用柱层析法(石油醚：乙酸乙酯＝5:1)分离得中间体6；
(6)：三口烧瓶中加入0.26g(1.05mmol)中间体4及10ml乙腈搅拌，缓慢加入0.25g中间体6，TLC跟踪反应至原料基本消失后停止反应，抽滤得白色固体，并用正己烷：乙酸乙酯＝100:1搅拌洗涤后，抽滤，正己烷洗涤得白色固体纯品。
实施例4：N-((2-(丁基氨基甲酰基)-6-氯-4-甲基苯基)氨基甲酰基)-3-氯-5-(三氟甲基)吡啶酰胺(I-1l)
Figure GDA0003542938740000081
(1)向50ml单口圆底烧瓶中加入1g(1mmol)3-氯-5-三氟甲基吡啶酸以及5ml溶剂，滴加几滴DMF的混合液并搅拌10min，缓慢加入0.675g(1.2mmol)草酰氯和DCM的混合液,滴加完毕后，在室温下搅拌3h后停止反应，将体系旋干后得中间体2；
(2)向50ml三口烧瓶中加入10ml浓氨水加热搅拌，待体系温度达60℃，缓慢滴加0.3g中间体2的二氯甲烷的混合液，滴加完毕，继续搅拌待反应完毕后停止反应，反应液用10％的NaOH水溶液及乙酸乙酯萃取两次，旋干得中间体3；
(3)在50ml单口圆底烧瓶中加入0.24g(1mmol)中间体3与5ml 1，2-二氯乙烷，室温搅拌，滴加0.23g(1.5mmol)草酰氯和2ml 1，2二氯乙烷的混合液，滴加完毕，加热，半小时后停止反应，脱溶，得中间体4待用；
(4)向100ml三口烧瓶中加入5g原料4及四氢呋喃室温搅拌，分次加入8.65g三光气，TLC跟踪反应待原料基本消失，脱溶，固体用正己烷溶液洗涤多次得中间体5；
(5)在50ml单口圆底烧瓶中加入0.5g中间体5及8ml乙腈，室温搅拌，逐滴加入甲胺的乙腈混合液直至固体固体消失后停止滴加，后用柱层析法(石油醚：乙酸乙酯＝5:1)分离得中间体6；
(6)：三口烧瓶中加入0.27g(1.05mmol)中间体4及10ml乙腈搅拌，缓慢加入0.25g中间体6，TLC跟踪反应至原料基本消失后停止反应，抽滤得白色固体，并用正己烷：乙酸乙酯＝100:1搅拌洗涤后，抽滤，正己烷洗涤得白色固体纯品。
实施例5：3-氯-N-((4-氯-2-(环丙基氨基)-6-甲基苯基)硫代氨基甲酰基)-5-(三氟甲基)吡啶酰胺(I-2a)的制备
Figure GDA0003542938740000091
(1)向50ml三口圆底烧瓶中加入1g(1mmol)的3-氯-5-(三氟甲基)吡啶甲酸以及6mL溶剂，滴加几滴DMF的混合液并搅拌10min，缓慢加入0.45mL(0.675g)(1.2mmol)草酰氯和6mLDCM的混合液,滴加完毕后，在室温下搅拌3h后停止反应，将体系旋干后得中间体2；
(2)向50ml三口烧瓶中加入143.38mg(1.2mmol)硫氰化钾，乙腈为溶剂，滴加PEG-400，冰盐条件下缓慢滴加中间体2和乙腈的混合液，20min后撤掉冰浴锅，继续反应半小时，停止反应。抽滤除去硫氰化钾，减压脱去乙腈溶剂，即得到中间体7，待用；
(3)向100ml三口烧瓶中加入3g(1mmol)原料4，四氢呋喃为溶剂，常温搅拌，分次加入4.80g(1mmol)三光气，TLC跟踪反应，待原料基本反应完全后停止反应，脱溶，抽滤，正己烷多次洗涤，得到中间体5；
(4)向50ml三口烧瓶中加入0.5g中间体5，乙腈为溶剂，室温搅拌，缓慢滴加环丙胺的乙腈混合液，至固体消失后停止滴加，柱层析分离得到中间体6；
(5)向50ml三口烧瓶中加入261.06mg(1.1mmol)中间体7，缓慢加入200mg(1mmol)中间体6，反应30min，停止反应，抽滤，用正己烷：乙酸乙酯＝100:1多次洗涤，抽滤，正己烷洗涤得固体产品，烘干，得目标化合物Ⅰ-2。
实施例6：N-((2-(丁基氨基甲酰基)-4-氯苯基)硫代氨基甲酰基)-3-氯-5-(三氟甲基)吡啶酰胺(I-2c)的制备
Figure GDA0003542938740000092
(1)向50ml三口圆底烧瓶中加入1g(1mmol)的3-氯-5-(三氟甲基)吡啶甲酸以及6mL溶剂，滴加几滴DMF的混合液并搅拌10min，缓慢加入0.45mL(0.675g)(1.2mmol)草酰氯和6mLDCM的混合液,滴加完毕后，在室温下搅拌3h后停止反应，将体系旋干后得中间体2；
(2)向50ml三口烧瓶中加入143.38mg(1.2mmol)硫氰化钾，乙腈为溶剂，滴加PEG-400，冰盐条件下缓慢滴加中间体2和乙腈的混合液，20min后撤掉冰浴锅，继续反应半小时，停止反应，抽滤除去硫氰化钾，减压脱去乙腈溶剂，即得到中间体7，待用；
(3)向100ml三口烧瓶中加入3g(1mmol)原料4，四氢呋喃为溶剂，常温搅拌，分次加入4.32g(1mmol)三光气，TLC跟踪反应，待原料基本反应完全后停止反应，脱溶，抽滤，正己烷多次洗涤，中间体5；
(4)向50ml三口烧瓶中加入0.5g中间体5，乙腈为溶剂，室温搅拌，缓慢滴加正丁胺的乙腈混合液，至固体消失后停止滴加，柱层析分离得到中间体6；
(5)向50ml三口烧瓶中加入258.74mg(1.1mmol)中间体7，缓慢加入200mg(1mmol)中间体6，反应30min，停止反应，抽滤，用正己烷：乙酸乙酯＝100:1多次洗涤，抽滤，正己烷洗涤得固体产品，烘干，得目标化合物Ⅰ-2。
实施例7：3-氯-N-((2-(环丙基氨基)-4,6-二氟苯基)硫代氨基甲酰基)-5-(三氟甲基)吡啶酰胺(I-2h)的制备
Figure GDA0003542938740000101
(1)向50ml三口圆底烧瓶中加入1g(1mmol)的3-氯-5-(三氟甲基)吡啶甲酸以及6mL溶剂，滴加几滴DMF的混合液并搅拌10min，缓慢加入0.45mL(0.675g)(1.2mmol)草酰氯和6mLDCM的混合液,滴加完毕后，在室温下搅拌3h后停止反应，将体系旋干后得中间体2；
(2)向50ml三口烧瓶中加入143.38mg(1.2mmol)硫氰化钾，乙腈为溶剂，滴加PEG-400，冰盐条件下缓慢滴加中间体2和乙腈的混合液，20min后撤掉冰浴锅，继续反应半小时，停止反应，抽滤除去硫氰化钾，减压脱去乙腈溶剂，即得到中间体7待用；
(3)向100ml三口烧瓶中加入3g(1mmol)原料4，四氢呋喃为溶剂，常温搅拌，分次加入5.14g(1mmol)三光气，TLC跟踪反应，待原料基本反应完全后停止反应，脱溶，抽滤，正己烷多次洗涤，中间体5；
(4)向50ml三口烧瓶中加入0.5g中间体5，乙腈为溶剂，室温搅拌，缓慢滴加环丙胺的乙腈混合液，至固体消失后停止滴加，柱层析分离得到中间体6；
(5)向50ml三口烧瓶中加入276.42mg(1.1mmol)中间体7，缓慢加入200mg(1mmol)中间体6，反应30min，停止反应，抽滤，用正己烷：乙酸乙酯＝100:1多次洗涤，抽滤，正己烷洗涤得固体产品，烘干，得目标化合物Ⅰ-2。
实施例8：3-氯-N-((2,4-二氯-6-((2,2-二氟乙基)氨基甲酰基)苯基)硫代氨基甲酰基)-5-(三氟甲基)吡啶酰胺(I-2m)
Figure GDA0003542938740000111
(1)向50ml三口圆底烧瓶中加入1g(1mmol)的3-氯-5-(三氟甲基)吡啶甲酸以及6mL溶剂，滴加几滴DMF的混合液并搅拌10min，缓慢加入0.45mL(0.675g)(1.2mmol)草酰氯和6mLDCM的混合液,滴加完毕后，在室温下搅拌3h后停止反应，将体系旋干后得中间体2；
(2)向50ml三口烧瓶中加入143.38mg(1.2mmol)硫氰化钾，乙腈为溶剂，滴加PEG-400，冰盐条件下缓慢滴加中间体2和乙腈的混合液，20min后撤掉冰浴锅，继续反应半小时，停止反应，抽滤除去硫氰化钾，减压脱去乙腈溶剂，即得到中间体7待用；
(3)向100ml三口烧瓶中加入3g(1mmol)原料4，四氢呋喃为溶剂，常温搅拌，分次加入4.32g(1mmol)三光气，TLC跟踪反应，待原料基本反应完全后停止反应，脱溶，抽滤，正己烷多次洗涤，中间体5；
(4)向50ml三口烧瓶中加入0.5g中间体5，乙腈为溶剂，室温搅拌，缓慢滴加2,2-二氟乙烷-1-胺的乙腈混合液，至固体消失后停止滴加，柱层析分离得到中间体6；
(5)向50ml三口烧瓶中加入218.00mg(1.1mmol)中间体7，缓慢加入200mg(1mmol)中间体6，反应30min，停止反应，抽滤，用正己烷：乙酸乙酯＝100:1多次洗涤，抽滤，正己烷洗涤得固体产品，烘干，得目标化合物Ⅰ-2。
所合成的目标化合物理化性质如下：
采用上述类似的方法，可以制备得到本案中其他优选的化合物。所合成的部分化合物的核磁谱图数据、物化性质等列如下：
Figure GDA0003542938740000112
3-氯-N-((2,4-二氯-6-(甲基氨基甲酰基)苯基)氨基甲酰基)-5-(三氟甲基)吡啶酰胺(I-1a)：淡黄色固体，熔点174-176℃，收率62％；1H NMR(400MHz,DMSO)δ10.63(s,1H),9.09(s,1H),8.66(s,1H),8.39(s,1H),7.89(s,1H),7.56(s,1H),2.72(d,J＝4.5Hz,3H).13C NMR(101MHz,DMSO)δ165.50,162.59,153.52,144.53(q,J＝4.6Hz),138.50,137.12(q,J＝4.0Hz),133.82,132.36,131.16,130.74,130.02,127.91(q,J＝33.8Hz),127.40,122.95(q,J＝272.9Hz),26.64.19F NMR(376MHz,DMSO)δ-60.87.HRMS(ESI):Calculated for C19H17O3N3[M+H]+:336.13427,found:336.13309.
Figure GDA0003542938740000124
3-氯-N-((2,4-二氯-6-(异丙基)苯基)氨基甲酰基)-5-(三氟甲基)吡啶酰胺(I-1b):淡黄色固体，熔点183-185℃，收率78％；1H NMR(400MHz,DMSO)δ12.34(s,1H),10.75(s,1H),9.07(d,J＝0.9Hz,1H),8.72(d,J＝1.1Hz,1H),8.22(d,J＝7.6Hz,1H),7.90(d,J＝2.3Hz,1H),7.55(d,J＝2.4Hz,1H),3.94(dq,J＝13.4,6.6Hz,1H),1.10(d,J＝6.6Hz,6H).13C NMR(101MHz,DMSO)δ163.65,159.07,157.53,152.60,144.62(q,J＝3.9Hz),138.12,137.10(q,J＝3.1Hz),133.65,132.97,130.84,129.78,128.25(q,J＝33.6Hz),124.48,122.87(q,J＝273.5Hz),41.63,22.48.19F NMR(376MHz,DMSO)δ-60.90.HRMS(ESI):Calculated for C19H17O3N3[M+H]+:336.13427,found:336.13309.
Figure GDA0003542938740000125
3-氯-N-((2-(环丙基氨基)-4-甲基苯基)氨基甲酰基)-5-(三氟甲基)吡啶酰胺(I-1c):米白色固体，熔点172-173℃，收率54％；1H NMR(400MHz,DMSO)δ12.27(s,1H),10.65(s,1H),9.09(d,J＝1.0Hz,1H),8.73(d,J＝1.2Hz,1H),8.32(d,J＝4.2Hz,1H),7.39(dd,J＝7.3,1.2Hz,1H),7.33(dd,J＝7.6,1.7Hz,1H),7.31–7.27(m,1H),2.75(td,J＝7.2,3.8Hz,1H),2.20(s,3H),0.68–0.62(m,2H),0.53–0.48(m,2H).13C NMR(101MHz,DMSO)δ168.64,163.39,159.49,157.03,152.39,144.63(q,J＝4.0Hz),137.24(q,J＝3.3Hz),136.02,133.55,132.67,132.61,129.95,128.31(q,J＝33.1Hz),127.33,126.46,122.87(q,J＝273.3Hz),23.24,18.67,6.21.19F NMR(376MHz,DMSO)δ-60.89.HRMS(ESI):Calculated for C19H17O3N3[M+H]+:336.13427,found:336.13309.
Figure GDA0003542938740000123
3-氯-N-((2,4-二氯-6-(环丙基氨基)苯基)氨基甲酰基)-5-(三氟甲基)吡啶酰胺(I-1d):米白色固体，熔点180-181℃收率68％；1H NMR(400MHz,DMSO)δ12.35(s,1H),10.83(s,1H),9.08(s,1H),8.74(s,1H),8.49(d,J＝3.9Hz,1H),7.90(d,J＝2.3Hz,1H),7.54(d,J＝2.3Hz,1H),2.73(td,J＝7.2,3.7Hz,1H),0.69–0.63(m,2H),0.55–0.49(m,2H).13C NMR(101MHz,DMSO)δ165.86,163.64,159.06,157.48,152.64,144.64(q,J＝4.6Hz),137.53,137.12(q,J＝4.2Hz),133.63,132.81,130.95,129.78,128.24(q,J＝33.4Hz),127.79,122.88(q,J＝273.6Hz),23.32,6.18.19F NMR(376MHz,DMSO)δ-60.88.HRMS(ESI):Calculated for C19H17O3N3[M+H]+:336.13427,found:336.13309.
Figure GDA0003542938740000131
N-((2-(丁基氨基甲酰基)-4,6-二氯苯基)氨基甲酰基)-3-氯-5-(三氟甲基)吡啶酰胺(I-1e):白色固体，熔点174-176℃，收率51％；1H NMR(400MHz,DMSO)δ10.58(s,1H),9.09(s,1H),8.68(s,1H),8.41(t,J＝5.5Hz,1H),7.89(d,J＝2.3Hz,1H),7.53(d,J＝2.3Hz,1H),3.17(dd,J＝12.7,6.7Hz,2H),1.46–1.39(m,2H),1.30–1.22(m,2H),0.79(t,J＝7.3Hz,3H).13C NMR(101MHz,DMSO)δ164.88,162.33,152.81,144.43(q,J＝4.7Hz),138.82,137.37(q,J＝3.3Hz),133.88,132.41,131.11,130.67,130.33,128.06(q,J＝33.2Hz),127.47,122.93(q,J＝273.5Hz),31.37,30.28,20.05,14.10.19F NMR(376MHz,DMSO)δ-60.89.
Figure GDA0003542938740000132
3-氯-N-((2,4-二氯-6-(丙基氨基)苯基)氨基甲酰基)-5-(三氟甲基)吡啶酰胺(I-1f):白色固体，熔点156-157℃，收率75％；1H NMR(400MHz,DMSO)δ12.33(s,1H),10.82(s,1H),9.07(s,1H),8.74(s,1H),8.43(t,J＝5.6Hz,1H),7.91(d,J＝2.3Hz,1H),7.56(d,J＝2.3Hz,1H),3.12(dd,J＝12.9,6.7Hz,2H),1.52–1.42(m,2H),0.86(t,J＝7.4Hz,3H).13C NMR(101MHz,DMSO)δ164.60,163.56,159.00,157.52,144.62(q,J＝4.0Hz),137.98,137.13(q,J＝3.6Hz),133.76,132.94,130.92,130.86,129.80,128.27(q,J＝33.3Hz),127.75,122.86(q,J＝273.6Hz),41.44,22.58,11.91.19FNMR(376MHz,DMSO)δ-61.06.HRMS(ESI):Calculated for C19H17O3N3[M+H]+:336.13427,found:336.13309.
Figure GDA0003542938740000141
3-氯-N-((2,4-二氯-6-(乙基氨基甲酰基)苯基)氨基甲酰基)-5-(三氟甲基)吡啶酰胺(I-1g):白色固体，熔点154-155℃，收率96％；1H NMR(400MHz,DMSO)δ12.33(s,1H),10.82(s,1H),9.07(d,J＝0.8Hz,1H),8.73(s,1H),8.42(t,J＝5.4Hz,1H),7.90(d,J＝2.3Hz,1H),7.57(d,J＝2.3Hz,1H),3.23–3.16(m,2H),1.07(t,J＝7.2Hz,3H).13C NMR(101MHz,DMSO)δ164.41,163.54,159.02,157.51,152.55,144.63(q,J＝3.8Hz),137.79,137.13(q,J＝3.4Hz),133.70,132.90,130.94,130.91,129.81,128.28(q,J＝33.3Hz),127.75,122.87(q,J＝273.5Hz),34.56,14.79.19F NMR(376MHz,DMSO)δ-60.91.HRMS(ESI):Calculated for C19H17O3N3[M+H]+:336.13427,found:336.13309.
Figure GDA0003542938740000142
1H),8.96(t,J＝5.2Hz,1H),8.74(s,1H),8.53(d,J＝9.0Hz,1H),7.92(d,J＝2.2Hz,1H),7.68(dd,J＝8.9,2.2Hz,1H),3.27(dd,J＝12.7,6.7Hz,2H),1.56–1.48(m,2H),1.39–1.29(m,2H),0.91(t,J＝7.3Hz,3H).13C NMR(101MHz,DMSO)δ166.75,163.36,159.45,156.74,152.20,144.64(q,J＝3.8Hz),137.35(q,J＝3.5Hz),136.63,132.37,130.01,128.53,128.36(q,J＝34.2Hz),123.40,122.85(q,J＝273.5Hz),122.28,31.20,20.12,14.16.19FNMR(376MHz,DMSO)δ-60.92.HRMS(ESI):Calculated for C19H17O3N3[M+H]+:336.13427,found:336.13309.
Figure GDA0003542938740000143
3-氯-N-((2-氯-6-(环己基)苯基)氨基甲酰基)-5-(三氟甲基)吡啶酰胺(I-1i):白色固体，熔点179-180℃，收率76％；1HNMR(400MHz,DMSO)δ12.78(s,1H),12.31(s,1H),9.10(s,1H),8.75(d,J＝12.4Hz,2H),8.52(d,J＝8.9Hz,1H),7.93(d,J＝2.0Hz,1H),7.68(dd,J＝8.9,1.9Hz,1H),1.82(s,2H),1.73(s,2H),1.61(d,J＝10.6Hz,1H),1.37–1.25(m,5H).13C NMR(101MHz,DMSO)δ165.92,163.41,159.48,156.69,152.27,144.66(q,J＝3.6Hz),137.33(q,J＝2.7Hz),136.57,132.31,129.96,128.68,128.51,128.34(q,J＝33.1Hz),123.61,122.86(q,J＝273.5Hz),49.12,32.49,25.63,25.28.19F NMR(376MHz,DMSO)δ-60.87.
Figure GDA0003542938740000151
3-氯-N-((2,4-二氯-6-(异丙基)苯基)氨基甲酰基)-5-(三氟甲基)吡啶酰胺(I-1j):白色固体，熔点189-190℃，收率84％；1H NMR(400MHz,DMSO)δ12.81(s,1H),12.31(s,1H),9.10(s,1H),8.77–8.73(m,2H),8.52(d,J＝8.9Hz,1H),7.94(s,1H),7.68(d,J＝8.4Hz,1H),4.11(dd,J＝13.0,6.5Hz,1H),1.18(d,J＝6.4Hz,6H).13C NMR(101MHz,DMSO)δ165.94,163.36,159.46,156.73,144.65(q,J＝3.4Hz),137.35(q,J＝3.2Hz),136.61,132.32,130.00,128.65,128.51,128.35(q,J＝31.9Hz),123.55,122.25,122.86(q,J＝273.7Hz),41.86,22.45.19F NMR(376MHz,DMSO)δ-60.87.HRMS(ESI):Calculated for C19H17O3N3[M+H]+:336.13427,found:336.13309.
Figure GDA0003542938740000152
3-氯-N-((2-氯-6-(环丙基氨基)-4-甲基苯基)氨基甲酰基)-5-(三氟甲基)吡啶酰胺(I-1k):白色固体，收率181-183℃，收率73％；1H NMR(400MHz,DMSO)δ12.25(d,J＝21.2Hz,1H),10.64(d,J＝21.4Hz,1H),9.07(d,J＝20.6Hz,1H),8.72(d,J＝20.5Hz,1H),8.43(d,J＝17.8Hz,1H),7.50(d,J＝19.7Hz,1H),7.35(d,J＝19.4Hz,1H),2.70(s,1H),2.19(d,J＝21.4Hz,3H),0.57(dd,J＝50.1,14.1Hz,4H).13C NMR(101MHz,DMSO)δ167.22,163.40,159.33,157.25,152.39,144.62(q,J＝3.7Hz),138.72,137.22(q,J＝3.4Hz),135.28,131.97,131.83,131.49,129.93,128.31(q,J＝33.3Hz).,126.15,122.87(q,J＝273.4Hz),23.28,18.40,6.16.19F NMR(376MHz,DMSO)δ-60.95.HRMS(ESI):Calculated for C19H17O3N3[M+H]+:336.13427,found:336.13309.
Figure GDA0003542938740000161
N-((2-(丁基氨基甲酰基)-6-氯-4-甲基苯基)氨基甲酰基)-3-氯-5-(三氟甲基)吡啶酰胺(I-1l):白色固体，熔点161-163℃，收率66％；1H NMR(400MHz,DMSO)δ12.24(s,1H),10.65(s,1H),9.08(d,J＝1.0Hz,1H),8.73(d,J＝1.2Hz,1H),8.37(t,J＝5.6Hz,1H),7.53(d,J＝2.0Hz,1H),7.39(d,J＝2.3Hz,1H),3.16(dd,J＝12.8,6.8Hz,2H),2.20(s,3H),1.48–1.40(m,2H),1.29(dq,J＝14.2,7.2Hz,2H),0.86(t,J＝7.3Hz,3H).13C NMR(101MHz,DMSO)δ165.91,163.31,159.25,157.27,152.29,144.61(q,J＝4.0Hz),138.80,137.26(q,J＝3.6Hz)135.70,131.91,131.80,129.96,128.34(q,J＝33.5Hz),126.05,122.85(q,J＝273.6Hz),39.21,31.40,20.05,18.42,14.11.19F NMR(376MHz,DMSO)δ-60.92.
Figure GDA0003542938740000162
3-氯-N-((2-氯-6-(乙基氨基甲酰基)-4-甲基苯基)氨基甲酰基)-5-(三氟甲基)吡啶酰胺(I-1m):白色固体，熔点169-171℃，收率78％；1H NMR(400MHz,DMSO)δ12.26(s,1H),10.68(s,1H),9.08(d,J＝1.0Hz,1H),8.73(d,J＝1.2Hz,1H),8.40(t,J＝5.5Hz,1H),7.53(d,J＝2.0Hz,1H),7.41(d,J＝2.3Hz,1H),3.23–3.17(m,2H),2.20(s,3H),1.07(t,J＝7.2Hz,3H).13C NMR(101MHz,DMSO)δ165.77,163.35,159.32,157.25,152.33,144.61(q,J＝3.6Hz),138.75,137.24(q,J＝3.7Hz),135.43,131.96,131.54,129.95,128.32(q,J＝33.5Hz),126.07,122.86(q,J＝273.5Hz),34.47,18.45,14.84.19FNMR(376MHz,DMSO)δ-60.91.HRMS(ESI):Calculated forC19H17O3N3[M+H]+:336.13427,found:336.13309.
Figure GDA0003542938740000163
3-氯-N-((2-氯-4-甲基-6-(甲基氨基甲酰基)苯基)氨基甲酰基)-5-(三氟甲基)吡啶酰胺(I-1n):白色固体，熔点156-158℃，收率80％；1H NMR(400MHz,DMSO)δ12.25(s,1H),10.74(s,1H),9.09(d,J＝1.0Hz,1H),8.73(d,J＝1.2Hz,1H),8.41(q,J＝4.4Hz,1H),7.53(d,J＝2.1Hz,1H),7.43(d,J＝2.4Hz,1H),2.71(d,J＝4.6Hz,3H),2.20(s,3H).13C NMR(101MHz,DMSO)δ166.55,163.31,159.31,157.20,152.30,144.62(q,J＝3.9Hz),138.71,137.26(q,J＝3.4Hz),134.92,132.07,131.44,129.97,128.33(q,J＝33.4Hz),126.05,122.86(q,J＝273.5Hz),26.66,18.51.19F NMR(376MHz,DMSO)δ-60.91.HRMS_(ESI):Calculated for C19H17O3N3[M+H]+:336.13427,found:336.13309.
Figure GDA0003542938740000171
3-氯-N-((4-甲基-2-(甲基氨基甲酰基)苯基)氨基甲酰基)-5-(三氟甲基)吡啶酰胺(I-1o):白色固体，熔点160-161℃，收率46％；1H NMR(400MHz,DMSO)δ12.25(s,1H),10.79(s,1H),9.09(d,J＝1.0Hz,1H),8.73(d,J＝1.2Hz,1H),8.33(d,J＝4.3Hz,1H),7.42–7.39(m,2H),7.30(t,J＝7.6Hz,1H),2.72(d,J＝4.6Hz,3H),2.20(s,3H).13C NMR(101MHz,DMSO)δ167.99,163.29,159.46,156.94,152.27,144.62(q,J＝3.6Hz),137.28(q,J＝3.4Hz),135.98,132.99,132.84,130.00,128.34(q,J＝33.3Hz),127.26,126.27,122.86(q,J＝273.4Hz),26.62,18.81.19F_NMR(376MHz,DMSO)δ-60.91.HRMS(ESI):Calculated for C19H17O3N3[M+H]+:336.13427,found:336.13309.
Figure GDA0003542938740000172
3-氯-N-((2-(环己基)-4-甲基苯基)氨基甲酰基)-5-(三氟甲基)吡啶酰胺(I-1p):白色固体，熔点161-163℃，收率60％；1H NMR(400MHz,DMSO)δ12.28(s,1H),10.58(s,1H),9.07(d,J＝1.0Hz,1H),8.73(d,J＝1.2Hz,1H),8.02(d,J＝8.0Hz,1H),7.40(d,J＝7.4Hz,1H),7.36(d,J＝6.1Hz,1H),7.31(t,J＝7.5Hz,1H),3.70–3.61(m,1H),2.20(s,3H),1.77(d,J＝10.8Hz,2H),1.69(d,J＝12.7Hz,2H),1.58(d,J＝12.9Hz,1H),1.32–1.08(m,5H). 13C NMR(101MHz,DMSO)δ166.37,163.48,159.49,157.08,152.51,144.61(q,J＝3.9Hz),137.18(q,J＝3.5Hz),136.04,134.30,132.48,129.86,128.28(q,J＝33.5Hz),127.52,126.61,122.87(q,J＝273.5Hz),48.53,32.64,25.67,25.17,18.64.19F NMR(376MHz,DMSO)δ-60.91.HRMS(ESI):Calculated for C19H17O3N3[M+H]+:336.13427,found:336.13309.
Figure GDA0003542938740000173
3-氯-N-((2-(乙基氨基甲酰基)-4-甲基苯基)氨基甲酰基)-5-(三氟甲基)吡啶酰胺(I-1q):白色固体，熔点158-160℃，收率50％；1H NMR(400MHz,DMSO)δ12.26(s,1H),10.71(s,1H),9.08(d,J＝0.9Hz,1H),8.73(d,J＝1.2Hz,1H),8.29(t,J＝5.5Hz,1H),7.41–7.37(m,2H),7.31(t,J＝7.5Hz,1H),3.24–3.17(m,2H),2.20(s,3H),1.07(t,J＝7.2Hz,3H).13C NMR(101MHz,DMSO)δ167.20,163.36,159.47,157.02,152.33,144.62(q,J＝3.8Hz),137.25(q,J＝3.1Hz).,136.02,133.65,132.68,129.96,128.32(q,J＝33.5Hz),127.37,126.35,122.86(d,J＝273.5Hz),34.36,18.73,14.98.19F NMR(376MHz,DMSO)δ-60.91.HRMS(ESI):Calculated for C19H17O3N3[M+H]+:336.13427,found:336.13309.
Figure GDA0003542938740000183
N-((2-(丁基氨基甲酰基)-4-甲基苯基)氨基甲酰基)-3-氯-5-(三氟甲基)吡啶酰胺(I-1r):白色固体，熔点145-147℃，收率54％；1H NMR(400MHz,DMSO)δ12.26(s,1H),10.68(s,1H),9.08(d,J＝1.0Hz,1H),8.73(d,J＝1.2Hz,1H),8.26(t,J＝5.7Hz,1H),7.40(d,J＝7.4Hz,1H),7.37(d,J＝6.2Hz,1H),7.31(t,J＝7.5Hz,1H),3.18(dd,J＝12.8,6.8Hz,2H),2.20(s,3H),1.48–1.40(m,2H),1.34–1.24(m,2H),0.86(t,J＝7.3Hz,3H).13CNMR(101MHz,DMSO)δ167.35,163.32,159.41,157.04,152.32,144.61(q,J＝3.9Hz),137.26(q,J＝3.4Hz).,136.05,133.91,132.59,129.97,128.34(q,J＝33.3Hz),127.43,126.35,122.86(q,J＝273.5Hz),39.12,31.52,20.06,18.70,14.12.19FNMR(376MHz,DMSO)δ-60.93.HRMS(ESI):Calculated forC19H17O3N3[M+H]+:336.13427,found:336.13309.
Figure GDA0003542938740000182
3-氯-N-((2-氯-4-甲基-6-(丙基氨基)苯基)氨基甲酰基)-5-(三氟甲基)吡啶酰胺(I-1s):白色固体，熔点188-190℃，收率89％；1H NMR(400MHz,DMSO)δ12.27(s,1H),10.65(s,1H),9.09(d,J＝0.9Hz,1H),8.73(d,J＝1.2Hz,1H),8.44(d,J＝4.1Hz,1H),7.52(d,J＝2.1Hz,1H),7.36(d,J＝2.3Hz,1H),2.77–2.69(m,1H),2.20(s,3H),0.68–0.62(m,2H),0.54–0.50(m,2H).13C NMR(101MHz,DMSO)δ167.22,163.43,159.35,157.26,152.42,144.62(dd,J＝7.8,3.8Hz).138.71,137.22(q,J＝3.3Hz),135.27,131.97,131.48,129.92,128.29(q,J＝33.4Hz),126.14,122.87(q,J＝273.5Hz),23.28,18.40,6.17.19FNMR(376MHz,DMSO)δ-60.90.HRMS(ESI):Calculated for C19H17O3N3[M+H]+:336.13427,found:336.13309.
Figure GDA0003542938740000191
3-氯-N-((2-氯-6-(环己基)-4-甲基苯基)氨基甲酰基)-5-(三氟甲基)吡啶酰胺(I-1t):白色固体，熔点189-191℃，收率85％；1H NMR(400MHz,DMSO)δ12.27(s,1H),10.58(s,1H),9.07(d,J＝0.8Hz,1H),8.74(d,J＝1.0Hz,1H),8.17(d,J＝7.9Hz,1H),7.52(d,J＝2.2Hz,1H),7.38(d,J＝2.3Hz,1H),3.63(dt,J＝14.1,8.7Hz,1H),2.20(s,3H),1.77(d,J＝10.5Hz,2H),1.68(d,J＝12.5Hz,2H),1.57(d,J＝12.7Hz,1H),1.31–1.08(m,5H).13C NMR(101MHz,DMSO)δ164.97,163.47,159.33,157.26,152.48,144.61(q,J＝3.8Hz),138.77,137.19(q,J＝3.5Hz),135.93,131.82,131.63,129.86,128.28(q,J＝33.3Hz),126.22,122.86(q,J＝273.4Hz),48.65,32.54,25.66,25.13,18.39.19F NMR(376MHz,DMSO)δ-60.90.HRMS(ESI):Calculated for C19H17O3N3[M+H]+:336.13427,found:336.13309.
Figure GDA0003542938740000192
3-氯-N-((2-氯-6-(异丙基)-4-甲基苯基)氨基甲酰基)-5-(三氟甲基)吡啶酰胺(I-1u):白色固体，熔点179-180℃，收率88％；1H NMR(400MHz,DMSO)δ12.26(s,1H),10.60(s,1H),9.07(d,J＝0.9Hz,1H),8.73(d,J＝1.2Hz,1H),8.18(d,J＝7.7Hz,1H),7.52(d,J＝2.0Hz,1H),7.39(d,J＝2.4Hz,1H),3.95(dq,J＝13.3,6.6Hz,1H),2.21(s,3H),1.10(d,J＝6.6Hz,6H).13C NMR(101MHz,DMSO)δ165.01,163.38,159.32,157.29,152.36,144.61(q,J＝3.9Hz),138.76,137.22(q,J＝3.3Hz),135.89,131.83,131.67,129.93,128.32(q,J＝33.4Hz),126.17,122.86(q,J＝273.6Hz).,41.47,22.51,18.39.19F NMR(376MHz,DMSO)δ-60.91.HRMS(ESI):Calculated for C19H17O3N3[M+H]+:336.13427,found:336.13309.
Figure GDA0003542938740000201
3-氯-N-((2-(异丙基)-4-甲基苯基)氨基甲酰基)-5-(三氟甲基)吡啶酰胺(I-1v):白色固体，熔点173-175℃，收率56％；1H NMR(400MHz,DMSO)δ12.28(s,1H),10.61(s,1H),9.08(d,J＝0.9Hz,1H),8.73(d,J＝1.2Hz,1H),8.04(d,J＝7.8Hz,1H),7.40(d,J＝7.4Hz,1H),7.36(d,J＝6.1Hz,1H),7.33–7.29(m,1H),3.98(dq,J＝13.3,6.6Hz,1H),2.20(s,3H),1.10(d,J＝6.6Hz,6H).13C NMR(101MHz,DMSO)δ166.42,163.42,159.49,157.10,152.41,144.62(q,J＝3.8Hz),137.22(q,J＝3.2Hz).,136.04,134.27,132.48,132.39,129.91,128.30(q,J＝33.9Hz),127.50,122.86(q,J＝273.5Hz),41.31,22.59,18.64.19FNMR(376MHz,DMSO)δ-60.90.HRMS(ESI):Calculated for C19H17O3N3[M+H]+:336.13427,found:336.13309.
Figure GDA0003542938740000202
3-氯-N-((2-(环丙基氨基)-4,6-二氟苯基)氨基甲酰基)-5-(三氟甲基)吡啶酰胺(I-1w):白色固体，熔点189-191℃，收率91％；1H NMR(400MHz,DMSO)δ12.32(s,1H),10.74(s,1H),9.08(d,J＝0.9Hz,1H),8.73(d,J＝1.2Hz,1H),8.54(d,J＝4.1Hz,1H),7.61–7.55(m,1H),7.28(d,J＝8.6Hz,1H),2.77(qd,J＝8.1,4.3Hz,1H),0.70–0.65(m,2H),0.57–0.53(m,2H).13C NMR(101MHz,DMSO)δ165.94,163.54,160.18(dd,J＝247.6,12.6Hz),159.12,157.48(dd,J＝252.5,12.6Hz),144.63(q,J＝3.7Hz),152.53,137.16(dd,J＝6.7,3.4Hz),135.67(dd,J＝8.4,1.6Hz),129.84,128.28(q,J＝33.3Hz),122.87(d,J＝273.4Hz),119.07(dd,J＝14.6,4.0Hz),111.92(dd,J＝23.9,2.9Hz),106.83(t,J＝25.8Hz),23.35,6.17.19F NMR(376MHz,DMSO)δ-60.91.HRMS(ESI):Calculated for C19H17O3N3[M+H]+:336.13427,found:336.13309.
Figure GDA0003542938740000203
3-氯-N-((2,4-二氯-6-((2,2-二氟乙基)氨基甲酰基)苯基)氨基甲酰基)-5-(三氟甲基)吡啶酰胺(I-1x):白色固体，熔点171-173℃，收率66％；1HNMR(400MHz,DMSO)δ12.31(s,1H),10.83(s,1H),9.07(d,J＝0.9Hz,1H),8.87(t,J＝6.0Hz,1H),8.73(d,J＝1.2Hz,1H),7.95(d,J＝2.3Hz,1H),7.59(d,J＝2.4Hz,1H),6.05(tt,J＝55.8,3.9Hz,1H),3.65–3.55(m,2H).13C NMR(101MHz,DMSO)δ165.44,163.57,158.96,152.57,144.61(q,J＝3.8Hz),137.14(q,J＝3.6Hz),136.74,133.76,132.88,131.42,131.00,129.80,128.27(q,J＝33.4Hz),127.92,122.87(q,J＝273.5Hz),114.84(t,J＝240.2Hz),41.88(t,J＝26.1Hz).19F NMR(376MHz,DMSO)δ-60.91,-121.22,-121.37.HRMS(ESI):Calculated forC19H17O3N3[M+H]+:336.13427,found:336.13309.
Figure GDA0003542938740000211
3-氯-N-((2-(乙基氨基甲酰基)-4,6-二氟苯基)氨基甲酰基)-5-(三氟甲基)吡啶酰胺(I-1y):白色固体，熔点172-173℃，收率63％；1H NMR(400MHz,H2O+D2O)δ12.32(s,1H),10.75(s,1H),9.08(d,J＝0.9Hz,1H),8.73(d,J＝1.2Hz,1H),8.50(t,J＝5.4Hz,1H),7.59(ddd,J＝10.2,8.8,2.8Hz,1H),7.33–7.30(m,1H),3.26–3.19(m,2H),1.09(t,J＝7.2Hz,3H).13C NMR(101MHz,DMSO)δ166.50,164.49,163.51,160.44(dd,J＝247.8,12.4Hz),159.02,157.42,157.51(dd,J＝253.0,12.6Hz),144.63(q,J＝3.8Hz),137.17(dd,J＝6.9,3.3Hz),135.83(d,J＝9.7Hz),128.29(q,J＝33.3Hz),122.86(q,J＝273.5Hz),119.12(dd,J＝14.4,3.9Hz),111.85(dd,J＝23.6,2.9Hz),106.84(t,J＝25.9Hz),34.58,14.81.19F NMR(376MHz,DMSO)δ-110.67(q,J＝8.4Hz),-112.28(t,J＝8.8Hz).HRMS(ESI):Calculated for C19H17O3N3[M+H]+:336.13427,found:336.13309.
Figure GDA0003542938740000212
3-氯-N-((4-氯-2-(环丙基氨基)-6-甲基苯基)硫代氨基甲酰基)-5-(三氟甲基)吡啶酰胺(I-2a):黄色固体，熔点226-227℃，收率62％；1H NMR(400MHz,DMSO)δ10.51(s,1H),9.08(d,J＝1.0Hz,1H),8.67(d,J＝1.3Hz,1H),8.47(d,J＝4.2Hz,1H),7.52(d,J＝2.1Hz,1H),7.35(d,J＝2.3Hz,1H),2.75(tq,J＝8.1,4.0Hz,1H),2.29(s,3H),0.67–0.60(m,2H),0.60–0.53(m,2H).13C NMR(101MHz,DMSO)δ167.33,162.60,154.21,144.50(q,J＝3.8Hz),139.01,136.96(q,J＝3.1Hz),136.58,131.88,131.62,131.24,129.79,127.76(q,J＝33.6Hz),125.94,122.98(q,J＝273.4Hz),23.31,18.52,6.14.19FNMR(376MHz,DMSO)δ-60.84.
Figure GDA0003542938740000221
色固体，熔点122-123℃，收率62％；1H NMR(400MHz,DMSO)δ10.50(s,1H),9.08(d,J＝1.0Hz,1H),8.68(d,J＝1.3Hz,1H),8.34(d,J＝4.2Hz,1H),7.40(dd,J＝7.1,1.6Hz,1H),7.34–7.24(m,2H),2.81–2.72(m,1H),2.30(s,3H),0.66–0.60(m,2H),0.59–0.52(m,2H).13CNMR(101MHz,DMSO)δ168.79,162.52,154.42,144.50(q,J＝3.8Hz),136.96(q,J＝3.3Hz),136.36,134.89,132.72,132.28,129.76,127.70(q,J＝33.2Hz),127.11,126.29,123.00(q,J＝273.4Hz),23.29,18.77,6.18.19F NMR(376MHz,DMSO)δ-60.85.
Figure GDA0003542938740000222
N-((2-(丁基氨基甲酰基)-4-氯苯基)硫代氨基甲酰基)-3-氯-5-(三氟甲基)吡啶酰胺(I-2c):灰色固体，熔点175-176℃，收率62％；1H NMR(400MHz,DMSO)δ12.69(s,1H),9.12(d,J＝1.0Hz,1H),8.94(t,J＝5.4Hz,1H),8.67(dd,J＝13.6,5.1Hz,2H),7.89(d,J＝2.5Hz,1H),7.67(dd,J＝9.0,2.5Hz,1H),3.26(dd,J＝12.7,7.0Hz,2H),1.55–1.48(m,2H),1.38–1.28(m,2H),0.90(t,J＝7.3Hz,3H).13C NMR(101MHz,DMSO)δ166.91,161.42,151.05,144.48(q,J＝3.7Hz),138.43(q,J＝3.4Hz),137.38,132.11,131.23,128.47(q,J＝33.4Hz),128.45,127.84,123.79,122.83(q,J＝273.6Hz),122.49,31.22,20.12,14.16.19F NMR(376MHz,DMSO)δ-60.96.
Figure GDA0003542938740000223
3-氯-N-((2,4-二氯-6-(甲基氨基甲酰基)苯基)硫代氨基甲酰基)-5-(三氟甲基)吡啶酰胺(I-2d):浅灰色固体，熔点190-191℃，收率62％；1HNMR(400MHz,DMSO)δ10.69(s,1H),9.09(d,J＝1.0Hz,1H),8.67(d,J＝1.3Hz,1H),8.47(d,J＝4.6Hz,1H),7.89(d,J＝2.4Hz,1H),7.57(d,J＝2.4Hz,1H),2.72(d,J＝4.6Hz,3H).13CNMR(101MHz,DMSO)δ165.45,162.62,153.62,144.54(q,J＝3.8Hz),138.55,137.08(q,J＝3.5Hz),133.87,132.40,131.11,130.75,129.97,127.89(q,J＝33.2Hz),127.47,122.96(q,J＝273.2Hz),26.64.19F NMR(376MHz,DMSO)δ-60.94.
Figure GDA0003542938740000231
3-氯-N-((4-氯-2-(乙基氨基甲酰基)-6-甲基苯基)硫代氨基甲酰基)-5-(三氟甲基)吡啶酰胺(I-2e):浅灰色固体，熔点222-224℃，收率62％；1HNMR(400MHz,DMSO)δ10.52(s,1H),9.08(d,J＝1.0Hz,1H),8.66(d,J＝1.3Hz,1H),8.41(t,J＝5.4Hz,1H),7.53(d,J＝2.0Hz,1H),7.38(d,J＝2.4Hz,1H),3.25–3.17(m,2H),2.30(s,3H),1.08(t,J＝7.2Hz,3H).13CNMR(101MHz,DMSO)δ165.93,162.61,154.17,144.55(q,J＝3.9Hz),139.05,136.98(q,J＝3.2Hz),136.69,131.98,131.62,131.26,129.77,127.76(q,J＝33.0Hz),125.87,122.98(q,J＝273.3Hz),34.48,18.55,14.89.19F NMR(376MHz,DMSO)δ-60.92.
Figure GDA0003542938740000232
N-((2-(丁基氨基甲酰基)-4-氯-6-甲基苯基)硫代氨基甲酰基)-3-氯-5-(三氟甲基)吡啶酰胺(I-2f):浅灰色固体，熔点189-190℃，收率62％；1H NMR(400MHz,DMSO)δ10.51(s,1H),9.07(d,J＝1.0Hz,1H),8.67(d,J＝1.3Hz,1H),8.41(t,J＝5.6Hz,1H),7.53(d,J＝2.0Hz,1H),7.37(d,J＝2.3Hz,1H),3.18(dd,J＝12.8,6.9Hz,2H),2.29(s,3H),1.48–1.41(m,2H),1.27(dt,J＝14.8,7.3Hz,2H),0.81(t,J＝7.3Hz,3H).13C NMR(101MHz,DMSO)δ166.08,162.48,153.77,144.48(q,J＝3.9Hz),139.10,137.11(q,J＝3.6Hz),136.81,131.98,131.60,131.28,129.95,127.83(q,J＝33.2Hz),125.87,122.96(q,J＝273.5Hz),39.27,31.42,20.07,18.54,14.13.19F NMR(376MHz,DMSO)δ-60.96.
Figure GDA0003542938740000233
3-氯-N-((4-氯-2-(甲基氨基甲酰基)苯基)硫代氨基甲酰基)-5-(三氟甲基)吡啶酰胺(I-2g):浅灰色固体，熔点198-200℃，收率62％；1H NMR(400MHz,DMSO)δ12.79(s,1H),9.13(d,J＝1.0Hz,1H),9.00(d,J＝4.3Hz,1H),8.67(d,J＝9.0Hz,2H),7.91(d,J＝2.5Hz,1H),7.67(dd,J＝9.0,2.5Hz,1H),2.78(d,J＝4.5Hz,3H).13C NMR(101MHz,DMSO)δ167.46,161.44,151.09,144.50(q,J＝3.8Hz),138.42(q,J＝3.1Hz),137.47,132.19,131.23,128.47,128.46(q,J＝33.6Hz),127.86,122.84(q,J＝273.6Hz),123.42,122.44,26.81.19FNMR(376MHz,DMSO)δ-60.96.
Figure GDA0003542938740000241
3-氯-N-((2-(环丙基氨基)-4,6-二氟苯基)硫代氨基甲酰基)-5-(三氟甲基)吡啶酰胺(I-2h):紫色固体，熔点193-194℃，收率62％；1H NMR(400MHz,DMSO)δ10.57(s,1H),9.08(d,J＝0.9Hz,1H),8.68(d,J＝1.2Hz,1H),8.59(d,J＝4.2Hz,1H),7.55(td,J＝10.1,2.8Hz,1H),7.29–7.22(m,1H),2.77(tq,J＝8.0,4.0Hz,1H),0.70–0.62(m,2H),0.62–0.50(m,2H).13C NMR(101MHz,DMSO)δ166.15,162.53,160.25(dd,J＝247.2,12.2Hz),157.77(dd,J＝252.8,12.5Hz),153.36,144.48(q,J＝3.8Hz),137.17(q,J＝3.5Hz),136.78(dd,J＝8.5,1.4Hz),130.10,127.96(q,J＝33.3Hz),122.95(q,J＝273.5Hz),119.28(dd,J＝14.5,4.0Hz),111.56(dd,J＝23.7,3.1Hz),106.46(t,J＝25.8Hz),23.35,6.14.19F NMR(376MHz,DMSO)δ-60.94,-111.31,-112.21.
Figure GDA0003542938740000242
3-氯-N-((4-氯-2-(环丙基氨基)苯基)硫代氨基甲酰基)-5-(三氟甲基)吡啶酰胺(I-2i):浅灰色固体，熔点≥300℃，收率62％；1H NMR(400MHz,DMSO)δ12.70(s,1H),9.14(s,1H),8.94(s,1H),8.69(s,1H),8.64(d,J＝8.9Hz,1H),7.87(s,1H),7.66(d,J＝8.8Hz,1H),2.87(s,1H),0.71(d,J＝6.1Hz,2H),0.64(s,2H).13C NMR(101MHz,DMSO)δ168.34,161.45,151.11,144.52(q,J＝4.7Hz),138.43(q,J＝2.8Hz),137.31,132.22,131.24,128.66,128.49(q,J＝35.1Hz),127.83,122.85(q,J＝273.8Hz),123.43,122.47,23.68,6.10.19F NMR(376MHz,DMSO)δ-60.93.
Figure GDA0003542938740000243
3-氯-N-((2,4-二氯-6-(丙基氨基)苯基)硫代氨基甲酰基)-5-(三氟甲基)吡啶酰胺(I-2j):浅灰色固体，熔点190-191℃，收率62％；1H NMR(400MHz,DMSO)δ10.60(s,1H),9.09(d,J＝0.9Hz,1H),8.67(d,J＝1.2Hz,1H),8.45(t,J＝5.6Hz,1H),7.90(d,J＝2.3Hz,1H),7.54(d,J＝2.3Hz,1H),3.14(dd,J＝12.9,6.8Hz,2H),1.54–1.40(m,2H),0.83(t,J＝7.4Hz,3H).13C NMR(101MHz,DMSO)δ164.95,162.44,153.12,144.48(q,J＝4.0Hz),138.74,137.26(q,J＝3.5Hz),133.84,132.38,131.11,130.69,130.19,127.99(q,J＝33.3Hz),127.47,122.94(q,J＝273.4Hz),41.46,22.53,11.91.19F NMR(376MHz,DMSO)δ-60.87.
Figure GDA0003542938740000251
3-氯-N-((4-氯-2-(环己基)苯基)硫代氨基甲酰基)-5-(三氟甲基)吡啶酰胺(I-2k):浅黄色固体，熔点208-209℃，收率62％；1H NMR(400MHz,DMSO)δ12.64(s,1H),9.13(s,1H),8.76–8.67(m,2H),8.64(d,J＝9.0Hz,1H),7.89(d,J＝2.4Hz,1H),7.66(dd,J＝9.0,2.3Hz,1H),3.76(s,1H),1.81(s,2H),1.74(s,2H),1.28(d,J＝16.1Hz,6H).13C NMR(101MHz,DMSO)δ166.08,161.44,151.12,144.56(q,J＝3.6Hz),138.42(q,J＝3.5Hz),137.36,132.08,131.20,128.78(q,J＝33.9Hz),128.61,127.82,123.93,122.46,122.85(q,J＝273.7Hz),49.01,32.49,25.63,25.28.19FNMR(376MHz,DMSO)δ-60.92.
Figure GDA0003542938740000252
N-((2-(丁基氨基甲酰基)-4,6-二氯苯基)硫代氨基甲酰基)-3-氯-5-(三氟甲基)吡啶酰胺(I-2l):浅灰色固体，熔点188-189℃，收率62％；1H NMR(400MHz,DMSO)δ10.59(s,1H),9.09(d,J＝1.0Hz,1H),8.68(d,J＝1.2Hz,1H),8.41(t,J＝5.6Hz,1H),7.89(d,J＝2.4Hz,1H),7.53(d,J＝2.4Hz,1H),3.17(dd,J＝12.7,6.9Hz,2H),1.42(dt,J＝19.5,7.2Hz,2H),1.25(dq,J＝14.4,7.3Hz,2H),0.79(t,J＝7.3Hz,3H).13CNMR(101MHz,DMSO)δ164.89,162.34,152.81,144.44(q,J＝3.5Hz),138.83,137.37(q,J＝3.3Hz),133.88,132.42,131.09,130.67,130.32,128.06(q,J＝33.1Hz),127.47,122.93(q,J＝273.4Hz),31.37,20.05,14.10.19F NMR(376MHz,DMSO)δ-60.88.
Figure GDA0003542938740000253
3-氯-N-((2,4-二氯-6-((2,2-二氟乙基)氨基甲酰基)苯基)硫代氨基甲酰基)-5-(三氟甲基)吡啶酰胺(I-2m):浅黄色固体，熔点215-216℃，收率62％；1H NMR(400MHz,DMSO)δ10.67(s,1H),9.09(d,J＝1.0Hz,1H),8.99(t,J＝6.0Hz,1H),8.67(d,J＝1.3Hz,1H),7.95(d,J＝2.4Hz,1H),7.57(d,J＝2.4Hz,1H),6.08(ddd,J＝55.9,29.9,4.0Hz,1H),3.66–3.55(m,2H).13C NMR(101MHz,DMSO)δ165.82,162.53,153.16,144.50(q,J＝3.5Hz),137.48,137.23(q,J＝3.5Hz),133.68,132.31,131.17,130.14,127.97(q,J＝33.3Hz),127.66,122.95(q,J＝273.5Hz),114.91(t,J＝240.3Hz),41.97(t,J＝26.9Hz).
Figure GDA0003542938740000261
3-氯-N-((4-氯-2-(环己基)-6-甲基苯基)硫代氨基甲酰基)-5-(三氟甲基)吡啶酰胺(I-2n):浅黄色固体。熔点170-171℃，收率62％；1H NMR(400MHz,DMSO)δ10.45(s,1H),9.08(s,1H),8.66(s,1H),8.24(d,J＝7.7Hz,1H),7.52(s,1H),7.35(s,1H),3.65(s,1H),2.29(s,3H),1.81(s,2H),1.67(s,2H),1.56(d,J＝12.0Hz,1H),1.25(d,J＝10.0Hz,5H).13C NMR(101MHz,DMSO)δ165.27,162.41,153.78,144.49(q,J＝4.3Hz),138.94,137.11(q,J＝3.4Hz),136.76,131.98,131.53,131.18,129.91,127.83(q,J＝33.2Hz),125.97,122.95(q,J＝273.6Hz),118.88,48.64,32.56,25.68,25.12,18.54.19F NMR(376MHz,DMSO)δ-60.86.
Figure GDA0003542938740000262
3-氯-N-((2-(环己基)-6-甲基苯基)硫代氨基甲酰基)-5-(三氟甲基)吡啶酰胺(I-2o):白色固体，熔点180-182℃，收率62％；1H NMR(400MHz,DMSO)δ10.43(s,1H),9.08(d,J＝1.0Hz,1H),8.66(d,J＝1.3Hz,1H),8.09(d,J＝7.9Hz,1H),7.40(dd,J＝7.3,1.2Hz,1H),7.35–7.27(m,2H),3.67(dd,J＝7.3,3.3Hz,1H),2.29(s,3H),1.80(d,J＝9.5Hz,2H),1.67(dd,J＝9.0,3.3Hz,2H),1.56(d,J＝12.4Hz,1H),1.28–1.17(m,5H).13C NMR(101MHz,DMSO)δ166.74,162.34,153.94,144.49(q,J＝3.8Hz),137.14(q,J＝3.5Hz),136.31,135.12,132.82,132.20,129.93,127.81(q,J＝33.2Hz),127.08,126.39,122.98(q,J＝273.4Hz),48.55,32.63,25.71,25.16,18.80.19F NMR(376MHz,DMSO)δ-60.85.
Figure GDA0003542938740000263
3-氯-N-((2-(乙基氨基甲酰基)-6-甲基苯基)硫代氨基甲酰基)-5-(三氟甲基)吡啶酰胺(I-2p):白色固体，熔点170-172℃，收率62％；1H NMR(400MHz,DMSO)δ10.48(s,1H),9.08(d,J＝1.0Hz,1H),8.66(d,J＝1.3Hz,1H),8.24(t,J＝5.5Hz,1H),7.41(dd,J＝7.4,1.0Hz,1H),7.35(dd,J＝7.6,1.5Hz,1H),7.30(t,J＝7.5Hz,1H),3.26–3.19(m,2H),2.30(s,3H),1.08(t,J＝7.2Hz,3H).13CNMR(101MHz,DMSO)δ167.43,162.48,154.26,144.54(q,J＝3.9Hz),137.01(q,J＝3.3Hz),136.36,134.88,132.88,132.30,129.79,127.74(q,J＝33.2Hz),127.10,126.14,122.99(q,J＝273.4Hz),34.40,18.81,15.01.19F NMR(376MHz,DMSO)δ-60.85.
Figure GDA0003542938740000271
3-氯-N-((2,4-二氯-6-(异丙基)苯基)硫代氨基甲酰基)-5-(三氟甲基)吡啶酰胺(I-2q):浅黄色固体，熔点168-169℃，收率62％；1H NMR(400MHz,DMSO)δ10.59(s,1H),9.09(s,1H),8.67(s,1H),8.29(d,J＝7.7Hz,1H),7.89(d,J＝2.3Hz,1H),7.52(d,J＝2.3Hz,1H),3.96(dq,J＝13.4,6.6Hz,1H),1.10(d,J＝6.6Hz,6H).13C NMR(101MHz,DMSO)δ164.03,162.38,153.03,144.47(q,J＝3.9Hz),138.85,144.47(q,J＝3.9Hz),137.30(q,J＝3.6Hz),133.76,132.37,131.04,130.60,130.21,128.03(q,J＝33.3Hz),127.55,122.93(q,J＝273.5Hz),41.59,22.54.19F NMR(376MHz,DMSO)δ-60.86.
Figure GDA0003542938740000272
3-氯-N-((4-氯-2-(异丙基)-6-甲基苯基)硫代氨基甲酰基)-5-(三氟甲基)吡啶酰胺(I-2r):浅黄色固体，熔点189-190℃，收率62％；1H NMR(400MHz,DMSO)δ10.45(s,1H),9.07(d,J＝0.8Hz,1H),8.66(d,J＝1.1Hz,1H),8.24(d,J＝7.7Hz,1H),7.53(d,J＝2.0Hz,1H),7.35(d,J＝2.3Hz,1H),4.05–3.92(m,1H),2.29(s,3H),1.11(d,J＝6.6Hz,6H).13C NMR(101MHz,DMSO)δ165.27,162.51,153.95,144.51(q,J＝4.0Hz),138.98,137.06(q,J＝3.6Hz),136.85,131.95,131.53,131.23,129.85,127.82(q,J＝33.3Hz),125.91,122.97(q,J＝273.6Hz),41.46,22.58,18.53.19F NMR(376MHz,DMSO)δ-60.84.
Figure GDA0003542938740000284
3-氯-N-((4-氯-2-甲基-6-(甲基氨基甲酰基)苯基)硫代氨基甲酰基)-5-(三氟甲基)吡啶酰胺(I-2s):白色固体，熔点190-191℃，收率62％；1HNMR(400MHz,DMSO)δ10.51(s,1H),9.08(d,J＝0.9Hz,1H),8.66(d,J＝1.2Hz,1H),8.33(d,J＝4.6Hz,1H),7.53(d,J＝2.1Hz,1H),7.39(d,J＝2.3Hz,1H),2.72(d,J＝4.6Hz,3H),2.29(s,3H).13C NMR(101MHz,DMSO)δ166.69,162.65,154.22,144.59(q,J＝4.0Hz),139.02,136.96(q,J＝3.3Hz),136.45,132.05,131.69,131.24,129.75,127.75(q,J＝33.2Hz),125.77,122.99(q,J＝273.5Hz),26.62,18.56.19F NMR(376MHz,DMSO)δ-60.84.
Figure GDA0003542938740000282
3-氯-N-((2-甲基-6-(甲基氨基甲酰基)苯基)硫代氨基甲酰基)-5-(三氟甲基)吡啶酰胺(I-2t):白色固体，熔点174-176℃，收率62％；1H NMR(400MHz,DMSO)δ10.52(s,1H),9.09(d,J＝0.9Hz,1H),8.66(d,J＝1.3Hz,1H),8.20(q,J＝4.2Hz,1H),7.41(d,J＝7.4Hz,1H),7.35(dd,J＝7.5,1.4Hz,1H),7.30(t,J＝7.5Hz,1H),2.73(d,J＝4.6Hz,3H),2.30(s,3H).13C NMR(101MHz,DMSO)δ168.16,162.54,154.40,144.59(q,J＝3.8Hz),136.97(q,J＝3.5Hz),136.37,134.64,132.94,132.37,129.74,127.70(q,J＝33.3Hz),127.10,126.06,123.00(q,J＝273.3Hz),26.61,18.83.19F NMR(376MHz,DMSO)δ-60.84.
Figure GDA0003542938740000283
3-氯-N-((2-(乙基氨基甲酰基)-4,6-二氟苯基)硫代氨基甲酰基)-5-(三氟甲基)吡啶酰胺(I-2u):白色固体，熔点168-169℃，收率62％；1H NMR(400MHz,DMSO)δ10.55(s,1H),9.08(d,J＝0.9Hz,1H),8.67(d,J＝1.2Hz,1H),8.50(t,J＝5.4Hz,1H),7.56(td,J＝10.2,2.8Hz,1H),7.28(d,J＝8.6Hz,1H),3.26–3.18(m,2H),1.09(t,J＝7.2Hz,3H).13C NMR(101MHz,DMSO)δ164.79,162.51,160.27(dd,J＝247.1,11.9Hz),157.78(dd,J＝252.5,12.6Hz),153.25,144.50(q,J＝3.6Hz),137.21(q,J＝2.8Hz),136.85(dd,J＝8.1,1.4Hz),130.11,127.97(q,J＝33.2Hz),122.94(q,J＝273.4Hz),119.39(dd,J＝14.3,3.7Hz),111.43(dd,J＝23.9,3.1Hz),106.47(t,J＝25.9Hz)34.56,14.84.19F NMR(376MHz,DMSO)δ-60.86.
Figure GDA0003542938740000291
3-氯-N-((2,4-二氟-6-(甲基氨基甲酰基)苯基)硫代氨基甲酰基)-5-(三氟甲基)吡啶酰胺(I-2v):白色固体，熔点171-172℃，收率62％；1H NMR(400MHz,DMSO)δ10.58(s,1H),9.09(s,1H),8.67(d,J＝1.1Hz,1H),8.47(d,J＝4.5Hz,1H),7.57(td,J＝10.2,2.7Hz,1H),7.29(d,J＝8.5Hz,1H),2.74(d,J＝4.6Hz,3H).13C NMR(101MHz,DMSO)δ165.52,162.50,160.24(dd,J＝246.0,11.7Hz),157.76(dd,J＝252.2,12.4Hz),153.31,144.53(q,J＝3.8Hz),137.20(q,J＝3.6Hz),136.54(dd,J＝8.3,1.9Hz),130.11,127.95(q,J＝33.0Hz),122.96(q,J＝273.5Hz),119.48(dd,J＝14.3,3.9Hz),111.39(dd,J＝23.6,3.1Hz),106.54(t,J＝25.8Hz),26.64.
Figure GDA0003542938740000292
3-氯-N-((2,4-二氟-6-(丙基氨基)苯基)硫代氨基甲酰基)-5-(三氟甲基)吡啶酰胺(I-2w):浅黄色固体，熔点159-160℃，收率62％；1H NMR(400MHz,DMSO)δ10.53(s,1H),9.08(d,J＝0.9Hz,1H),8.67(d,J＝1.2Hz,1H),8.51(t,J＝5.6Hz,1H),7.57(td,J＝10.2,2.8Hz,1H),7.28(dd,J＝7.2,1.2Hz,1H),3.16(dd,J＝12.9,6.8Hz,2H),1.55–1.44(m,2H),0.85(t,J＝7.4Hz,3H).13C NMR(101MHz,DMSO)δ164.98,162.47,160.31(dd,J＝239.8,7.3Hz),157.77(dd,J＝244.7,6.8Hz),153.11,144.48(q,J＝3.6Hz),137.26(q,J＝3.5Hz),136.92(dd,J＝8.3,1.5Hz),130.18,127.99(q,J＝33.3Hz),122.94(q,J＝273.5Hz),119.39(dd,J＝14.2,3.8Hz),111.45(dd,J＝23.7,3.5Hz),106.46(t,J＝25.9Hz),41.45,22.55,11.90.
Figure GDA0003542938740000293
3-氯-N-((2,4-二氟-6-(异丙基)苯基)硫代氨基甲酰基)-5-(三氟甲基)吡啶酰胺(I-2x):浅黄色固体，熔点150-151℃，收率62％；1H NMR(400MHz,DMSO)δ10.52(s,1H),9.08(s,1H),8.68(s,1H),8.35(d,J＝7.6Hz,1H),7.59–7.53(m,1H),7.26(d,J＝8.4Hz,1H),3.99(tt,J＝13.3,6.8Hz,1H),1.12(d,J＝6.6Hz,6H).19FNMR(376MHz,DMSO)δ-60.87.13C NMR(101MHz,DMSO)δ164.08,162.51,160.28(dd,J＝247.8,12.3Hz),157.80(dd,J＝252.3,13.0Hz),153.16,144.49(q,J＝3.9Hz),137.24(q,J＝3.7Hz),130.13,127.99(q,J＝32.9Hz),122.94(q,J＝273.5Hz),119.28(dd,J＝14.2,3.7Hz),111.55(d,J＝24.0Hz),106.36(t,J＝26.2Hz),41.64,22.54.19F NMR(376MHz,DMSO)δ-60.87,-111.31,-112.27.
以抗小菜蛾、褐飞虱、烟草花叶病毒(Tobacco Mosaic Virus,TMV)及黄瓜花叶病毒(CMV)的活性为例，对本发明化合物的活性及其应用进行说明。但并不限定本发明化合物抗其他病毒的应用。
实施例9：对小菜蛾的杀虫活性测试
配制好的一定浓度的药液，再剪出匀称(直径为2.00cm)的新鲜圆形甘蓝叶片，然后用镊子轻轻地将叶片置于药液中浸渍10s后转移到带有滤纸的培养皿内(该培养皿预先用二次水浸湿以保持甘蓝叶片的新鲜程度)晾干待用。之后用毛笔接入(过程必须保证所有幼虫均接在叶片上)10头/皿2龄幼虫(试虫需进行5-6h的饥饿处理)，最后放置22±1℃的养虫室中恒温饲养，3d后统计死亡虫数并计算虫口死亡率(以毛笔触动虫体，无反应视为死亡)。对照组共计3组(CK组)。
杀虫活性测试结果表明，在质量浓度为500mg/L时，目标化合物I-1a、I-1b、I-1d、I-1e、I-1f、I-1j、I-1k、I-1l、I-1m、I-1n、I-1s、I-1t、I-1u、I-1w、I-1x、I-1y，I-2a、I-2d、I-2e、I-2f、I-2j、I-2n、I-2q、I-2r、I-2s、I-2t、I-2u、I-2w、I-2x对小菜蛾具有大于80％的致死活性。
实施例10：对褐飞虱的杀虫活性测试
配制好的一定浓度的药液，用水稻苗于药液中浸渍10s后，晾干待用。之后用转移器将褐飞虱2龄幼虫20头(试虫需进行5-6h的饥饿处理)转移到浸药的水稻苗上，最后放置22±1℃的养虫室中恒温饲养，72后统计死亡虫数并计算虫口死亡率(以毛笔触动虫体，无反应视为死亡)。
测试结果表明，在质量浓度为500mg/L时，目标化合物I-1c、I-1d、I-1f、I-1j、I-1k、I-1l、I-1n、I-1s、I-1t、I-1u、I-1x、I-1y，I-2a、I-2f、I-2j、I-2n、I-2q、I-2u、I-2w、I-2x对褐飞虱具有大于75％的致死活性。
实施例11：抗烟草花叶病毒(TMV)生物活性测试
(1)TMV病毒的纯化
参照文献报道方法，选择接种TMV病毒时间在三周以上的的烟草叶片，冰浴条件下，将其在0.2M磷酸盐缓冲液中进行研磨，然后通过双层纱布过滤得提取液。向其加入丁醇后搅拌15min，4℃，10000rpm，离心20min得上清液，加入聚乙二醇(PEG)和氯化钠，搅拌1h，在4℃下，10000rpm，离心20min取沉淀，加入0.01M PBS，搅拌1h，4℃，10000rpm，离心15min取上清液，加入PEG和氯化钠，搅拌1h，4℃，10000rpm，离心20min取沉淀加入0.01MPBS搅拌1h，4℃，10000rpm，离心5min取上清，即得TMV病毒提取液。用紫外分光光度计估算260nm处的吸光度值。
病毒浓度＝(A260×稀释比例)/E1cm 0.1％,260nm
(2)目标化合物对于TMV病毒的活体治疗活性
选择左右叶片大小及年龄相同的烟草叶子，将整个叶片洒上薄厚均匀的金刚砂后在整个叶片上接种TMV病毒。30min后，用水将叶子上的金刚砂洗涤干净并自然晾干。之后将一定浓度的化合物溶液涂抹在左侧，并将溶剂涂抹在右侧作为对照。计数接种后3至4天出现的局部病变的数量。每个化合物进行三次重复。
(3)目标化合物对于TMV病毒的活体保护活性
选择左右叶片大小及年龄相同的烟草叶子，将一定浓度的化合物溶液涂抹在左侧，溶剂涂抹在烟草叶子的右侧作为对照。20-22小时后，将整个叶片洒上薄厚均匀的金刚砂并在整个叶片上接种TMV病毒。30min后，用水将叶子上的金刚砂洗涤干净。计数接种后3至4天出现的局部病变的数量。每个化合物进行三次重复。
(4)目标化合物对于TMV病毒的活体钝化活性
通过以相同体积病毒与化合物溶液混合30min来抑制病毒。选择左右叶片大小及年龄相同的烟草叶子，对整个叶片洒上均匀的金刚砂后将涂施病毒与等体积溶剂(DMSO和缓冲液)的混合液接种在烟草叶子的左侧，溶剂和病毒的混合物接种叶子的右侧作为对照。计数接种后3至4天出现的局部病变数。每个化合物进行三次重复。
(5)结果调查与分析
3至4天后，计数叶片左右出现的局部病斑数，按照如下公式计算抑制率(“av”表示平均值)。
Figure GDA0003542938740000311
经过上述步骤，化合物在质量浓度为500mg/L时，目标化合物I-1a、I-1b、I-1d、I-1e、I-1f、I-1j、II-1n、I-1s、I-1t、I-1u、I-1w、I-1x、I-1y，I-2a、I-2d、I-2e、I-2f、I-2j、I-2n、I-2q、I-2r、I-2t、I-2u、I-2w、I-2x对TMV具有大于50％的抗病毒治疗活性。
目标化合物I-1b、I-1c、I-1d、I-2r、I-2t、I-2u、I-2y对TMV具有大于60％的抗病毒保护活性。
目标化合物I-1a、I-1b、I-1c、I-1d、I-1e、I-1f、I-1j、I-1t、I-1u、I-1y、I-1z、I-2a、I-2d、I-2e、I-2f、I-2j、I-mj、I-2n、I-2q、I-2r、I-2t、I-2u、I-2y、I-2z对TMV具有大于80％的抗病毒钝化活性。
实施例12：抗黄瓜花叶病毒(CMV)生物活性测试
采用半叶枯斑法，以黄瓜花叶病毒为研究对象，市售宁南霉素为对照药剂，对目标化合物进行抗病毒活性测试对CMV的活体钝化作用
通过以相同体积病毒与化合物溶液混合30min来抑制病毒。选择左右叶片大小及年龄相同的苋色黎叶子，对整个叶片洒上均匀的金刚砂后将病毒与等体积溶剂(DMSO和缓冲液)的混合液接种在烟草叶子的左侧，溶剂和病毒的混合物接种叶子的右侧作为对照，30min后，洗去叶片上的金刚砂，自然晾干。计数接种后6至7天出现的局部病变数。每个化合物进行三次重复。
经过上述步骤，结果表明化合物在质量浓度为500mg/L时，目标化合物I-1a、I-1b、I-1c、I-1d、I-1e、I-1f、I-1j、I-1t、I-1u、I-1y、I-2f、I-2j、I-mj、I-2a～I-2f、I-2h、I-2i、I-2s、I-2t、I-2y、I-2z对TMV具有大于75％的抗病毒钝化活性。

Claims (4)

1.一种含三氟甲基吡啶的酰基硫脲或酰基脲衍生物，其通式如Ⅰ所示：
Figure FDA0003542938730000011
在通式Ⅰ所示的化合物中，R1为Cl；R2为3-甲基，5-氯，5-氯-3-甲基、3,5-二氯或3,5-二氟；R3为甲基、乙基、正丙基、异丙基、环丙基、环己基 、2,2-二氟乙基或2,2,2-三氟乙基； X为氧或硫 。
2.如权利要求1所述的含三氟甲基吡啶的酰基硫脲或酰基脲衍生物在杀虫剂或抗植物病毒剂中的应用。
3.根据权利要求2所述的含三氟甲基吡啶的酰基硫脲或酰基脲衍生物在制备防治小菜蛾、褐飞虱的杀虫剂中的应用。
4.根据权利要求2所述的含三氟甲基吡啶的酰基硫脲或酰基脲衍生物在制备防治植物病毒病TMV和CMV的抗植物病毒剂中的应用。
CN201910810477.9A 2019-08-29 2019-08-29 一种含三氟甲基吡啶的酰基硫脲或酰基脲类衍生物及其应用 Active CN110526863B (zh)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201910810477.9A CN110526863B (zh) 2019-08-29 2019-08-29 一种含三氟甲基吡啶的酰基硫脲或酰基脲类衍生物及其应用

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201910810477.9A CN110526863B (zh) 2019-08-29 2019-08-29 一种含三氟甲基吡啶的酰基硫脲或酰基脲类衍生物及其应用

Publications (2)

Publication Number Publication Date
CN110526863A CN110526863A (zh) 2019-12-03
CN110526863B true CN110526863B (zh) 2022-05-03

Family

ID=68665244

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201910810477.9A Active CN110526863B (zh) 2019-08-29 2019-08-29 一种含三氟甲基吡啶的酰基硫脲或酰基脲类衍生物及其应用

Country Status (1)

Country Link
CN (1) CN110526863B (zh)

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114656402B (zh) * 2022-04-11 2024-01-30 青岛科技大学 一种含氟烟酰脲类化合物及其用途
CN114805197B (zh) * 2022-04-11 2023-07-11 青岛科技大学 一种含氟吡啶酰基脲类杀虫杀螨剂
CN116439254A (zh) * 2023-03-20 2023-07-18 武汉朗克环境科技有限公司 一种含三氟甲基吡啶酰胺衍生物的混合药剂及其制备方法和应用
CN116283753A (zh) * 2023-03-20 2023-06-23 武汉朗克环境科技有限公司 一种三氟甲基吡啶酰胺衍生物及其制备方法和应用

Citations (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4946854A (en) * 1987-12-07 1990-08-07 Ciba-Geigy Corporation 3-aminobenzoylphenylureas useful for controlling parasites and insects that attack domestic animals and livestock
US5155135A (en) * 1988-12-21 1992-10-13 Shell Internationale Research Maatschappij, B.V. Benzamide compounds, their preparation and their use as pesticides
CN1653048A (zh) * 2002-05-16 2005-08-10 拜尔作物科学有限公司 吡啶甲酰胺衍生物及其作为杀虫剂的用途
WO2007066496A1 (en) * 2005-12-07 2007-06-14 Sumitomo Chemical Company, Limited Benzoylurea compound and use thereof
CN102276580A (zh) * 2011-06-02 2011-12-14 南开大学 吡唑甲酰基硫脲衍生物与制备方法和应用
KR20120079616A (ko) * 2011-01-05 2012-07-13 한국과학기술연구원 디페닐 유도체를 포함하는 항균제
WO2014046544A1 (en) * 2012-09-21 2014-03-27 Aapa B.V. Substituted 3-heteroaryloxy-3-(hetero)aryl-propylamines as serotonin transporter and serotonin ht2c receptor modulators
CN106748985A (zh) * 2016-12-04 2017-05-31 山东东方农药科技实业有限公司 一种氟啶脲的合成方法及其用于制备杀虫剂的用途
CN107759518A (zh) * 2017-07-27 2018-03-06 贵州大学 一种含三氟甲基吡啶的邻苯二甲酰胺衍生物及其应用
CN108912056A (zh) * 2018-08-10 2018-11-30 海南大学 一种新型苯甲酰基嘧啶脲类化合物及其制备和应用
CN110452234A (zh) * 2019-08-29 2019-11-15 贵州大学 一种含三氟甲基吡啶二甲酰胺的席夫碱的衍生物及其应用

Patent Citations (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4946854A (en) * 1987-12-07 1990-08-07 Ciba-Geigy Corporation 3-aminobenzoylphenylureas useful for controlling parasites and insects that attack domestic animals and livestock
US5155135A (en) * 1988-12-21 1992-10-13 Shell Internationale Research Maatschappij, B.V. Benzamide compounds, their preparation and their use as pesticides
CN1653048A (zh) * 2002-05-16 2005-08-10 拜尔作物科学有限公司 吡啶甲酰胺衍生物及其作为杀虫剂的用途
CN101230038A (zh) * 2002-05-16 2008-07-30 拜尔作物科学有限公司 吡啶甲酰胺衍生物及其作为杀虫剂的用途
WO2007066496A1 (en) * 2005-12-07 2007-06-14 Sumitomo Chemical Company, Limited Benzoylurea compound and use thereof
TW200804250A (en) * 2005-12-07 2008-01-16 Sumitomo Chemical Co Benzoylurea compound and use thereof
KR20120079616A (ko) * 2011-01-05 2012-07-13 한국과학기술연구원 디페닐 유도체를 포함하는 항균제
CN102276580A (zh) * 2011-06-02 2011-12-14 南开大学 吡唑甲酰基硫脲衍生物与制备方法和应用
WO2014046544A1 (en) * 2012-09-21 2014-03-27 Aapa B.V. Substituted 3-heteroaryloxy-3-(hetero)aryl-propylamines as serotonin transporter and serotonin ht2c receptor modulators
CN106748985A (zh) * 2016-12-04 2017-05-31 山东东方农药科技实业有限公司 一种氟啶脲的合成方法及其用于制备杀虫剂的用途
CN107759518A (zh) * 2017-07-27 2018-03-06 贵州大学 一种含三氟甲基吡啶的邻苯二甲酰胺衍生物及其应用
CN108912056A (zh) * 2018-08-10 2018-11-30 海南大学 一种新型苯甲酰基嘧啶脲类化合物及其制备和应用
CN110452234A (zh) * 2019-08-29 2019-11-15 贵州大学 一种含三氟甲基吡啶二甲酰胺的席夫碱的衍生物及其应用

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
杀虫剂氟啶脲的合成;陈华等;《精细化工中间体》;20130428(第02期);第20-21页 *

Also Published As

Publication number Publication date
CN110526863A (zh) 2019-12-03

Similar Documents

Publication Publication Date Title
CN110526863B (zh) 一种含三氟甲基吡啶的酰基硫脲或酰基脲类衍生物及其应用
CN103819413B (zh) 含喹唑啉酮芳氧基的戊二烯酮类化合物及制备方法和应用
CN112062759B (zh) 含乙砜基吡啶联1,2,4-噁二唑取代苯甲酰胺类化合物及其制备方法和应用
JPH07121911B2 (ja) ４（１ｈ）−ピリジノン誘導体および農園芸用殺菌剤
CN103554080A (zh) 含杂环基团的1,4-戊二烯-3-酮肟酯类化合物及其制备方法和应用
CN104402819B (zh) 一类双吡唑酰胺衍生物的制备及其在治理水稻黑条矮缩病中的应用
CN106543139B (zh) 一种三唑酮类化合物及其用途
CN102285979A (zh) N-(2-(取代苯并噻唑-2-氨基甲酰基)-苯基)-取代吡唑甲酰胺类化合物及其制备方法和用途
CN110452234B (zh) 一种含三氟甲基吡啶二甲酰胺的席夫碱的衍生物及其应用
CN103570672B (zh) 一种苯基取代噻吩甲酰肼类化合物及其制备方法和应用
CN111226956B (zh) 3,6-二取代咪唑[1,2-b]哒嗪类衍生物在制备抑制植物病原真菌杀菌剂中的应用
CN100569756C (zh) 具有除草活性的3-取代氨基哒嗪类衍生物及其制备方法
JPS63225364A (ja) アラルキルアミノピリミジン誘導体、その製造法並びに該誘導体を有効成分とする殺虫剤、殺ダニ剤及び殺菌剤
CN103664795A (zh) 哒嗪酮类化合物及其用途
JPS63290865A (ja) 複素環式ネオフアン同族体、それらの製造方法および有害生物殺滅剤としてのそれらの用途
CN110964037B (zh) 含嘧啶并环类化合物及其制备方法和用途
CN111454202B (zh) 一种含五氟硫基的杂芳基甲酰苯胺类化合物及其制备方法与用途
CN113387942A (zh) 一种吡唑羧酸酯类化合物及其应用
JP2517992B2 (ja) ピリジルピリミジン誘導体およびそれを有効成分とする植物病害防除剤
CN110294751B (zh) 具生物活性的咪唑[4,5-b]并吡啶类化合物及其制备方法和应用
JPH0276846A (ja) シアノ酢酸アミド誘導体およびその用途
CN111747946B (zh) 5-苯并呋喃-1,3,4-噻二唑-2-取代酰胺类化合物及其制备方法与应用
CN111303062B (zh) 一种苯甲酰胺类化合物及其作为除草剂的用途
CN110872302B (zh) 含嘧啶的螺环类化合物及其用途
JPS625428B2 (zh)

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
GR01 Patent grant
GR01 Patent grant