CN112174937A - 3-(5-咪唑基)吲哚类化合物及其制备方法和应用 - Google Patents

3-(5-咪唑基)吲哚类化合物及其制备方法和应用 Download PDF

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CN112174937A
CN112174937A CN202011119149.3A CN202011119149A CN112174937A CN 112174937 A CN112174937 A CN 112174937A CN 202011119149 A CN202011119149 A CN 202011119149A CN 112174937 A CN112174937 A CN 112174937A
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张明智
高雅
黄代钏
谭隽杨
章维华
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Abstract

本发明公开了如式Ⅰ所示的3‑(5‑咪唑基)吲哚类化合物。本发明3‑(5‑咪唑基)吲哚类化合物具有良好的杀菌活性，可以运用到由真菌、细菌和病毒引起的农作物病害中，表现出了高效和/或广谱的杀菌活性。本发明还公开了3‑(5‑咪唑基)吲哚类化合物在杀灭农作物致病菌中的应用。

Description

3-(5-咪唑基)吲哚类化合物及其制备方法和应用
技术领域
本发明属于农用杀菌剂领域，涉及3-(5-咪唑基)吲哚类化合物及其制备方法和应用。
背景技术
目前，多个商品化杀菌剂如多菌灵、啶酰菌胺出现了严重的抗性问题，亟待创制新型化学结构和作用机理的杀菌剂。
发明内容
本发明的目的是基于活性天然产物设计合成了一系列新型3-(5-咪唑基)吲哚类化合物，对目标化合物进行了杀菌活性测试，测试结果表明，化合物都对多种常见农作物病菌表现出抑制活性。
本发明的目的是通过以下技术方案实现的：
如式Ⅰ所示的3-(5-咪唑基)吲哚类化合物：
Figure BDA0002731380150000011
其中，R选自C1～C4直链或支链烷基、C3～C6环烷基、取代或未取代的苯基取代的C1～C2烷基、C1～C2烷氧基取代的C1～C2烷基、5元～6元含氮杂环取代的C1～C2烷基；所述的取代苯基的取代基为邻、间、对位取代的或者多取代的C1～C2烷基、C1～C2烷氧基、卤素取代的C1～C2烷基、F、Cl、Br；
X选自H、Cl、Br。
优选的，R选自C3～C4直链或支链烷基、环己烷基、苄基、取代苯基取代的甲基；所述的取代苯基的取代基为邻、间、对位取代的甲基、甲氧基、三氟甲基、F、Cl、Br。
进一步优选的，X选自H，R选自正丁基、环己烷基、苄基、取代苯基取代的甲基；所述的取代苯基的取代基为对位取代的甲基、甲氧基、三氟甲基、F、Cl、Br或邻位取代的F；
X选自Cl，R选自正丁基、1-异丁基、环己烷基、苄基、取代苯基取代的甲基；所述的取代苯基的取代基为对位取代的甲基、甲氧基、F、Cl、Br或邻位取代的F；
X选自Br，R选自C3～C4直链烷基、环己烷基、苄基、取代苯基取代的甲基；所述的取代苯基的取代基为对位取代的甲基、甲氧基、F、Cl、Br或间位取代的F或邻位取代的甲基、甲氧基、F。
本发明的另一个目的是提供所述的3-(5-咪唑基)吲哚类化合物的制备方法，X选自H时，合成路线如下：
Figure BDA0002731380150000021
以无水甲醇和无水乙二醇二甲醚(DEM)为溶剂，常温下，吲哚-3-甲醛与伯胺(RNH2)反应生成亚胺，再在温度40～60℃下，在K2CO3的作用下，TosMIC(对甲基磺酰甲基异腈)与亚胺反应生成式Ⅰa所示的3-(5-咪唑基)吲哚类化合物；其中，所述的吲哚-3-甲醛与伯胺的摩尔比为1:1～2，优选为1:1.5；所述的吲哚-3-甲醛与TosMIC的摩尔比为1:1～2，优选为1:1.5；所述的吲哚-3-甲醛与K2CO3的摩尔比为1:1～2，优选为1:1.5。
X选自Cl、Br时，合成路线如下：
Figure BDA0002731380150000022
以四氢呋喃和四氯化碳体积比为1:1的混合溶剂为溶剂，在温度40～60℃下，化合物Ⅰa与NCS或NBS反应生成式Ⅰb所示的3-(5-咪唑基)吲哚类化合物；其中，化合物Ⅰa与NCS或NBS的摩尔比为1:1～2，优选为1:1.1。
本发明基于Van Leusen咪唑合成反应，吲哚-3-甲醛与含有不同取代基的伯胺反应生成亚胺，而后TosMIC(对甲基磺酰甲基异腈)在45～50℃与亚胺发生反应生成咪唑环。由于亚胺的不稳定性，反应的温度直接影响到产率。温度高可以提高反应速率，但是较高的温度会使亚胺分解，不仅使产率下降，也会产生许多副产物，难以分离。
本发明所述的3-(5-咪唑基)吲哚类化合物表现出了高效和/或广谱的杀菌活性，对番茄早疫病菌(Alternaria solani)、草莓灰霉病菌(Botrytis cinrea)、苹果斑点病菌(Alternaria leaf spot)、水稻纹枯病菌(Rhizoctonia solani)、小麦赤霉病菌(Gibberella zeae)、黄瓜炭疽病菌(Colletotrichum lagenarium)具有杀菌活性，可以用于防治由真菌、细菌和病毒引起的农作物病害，尤其是在本发明最优选技术方案的3-(5-咪唑基)吲哚类化合物，杀菌活性至少可达到60％，具有进一步研究开发的潜力。因此，本发明的另一个目的是提供所述的3-(5-咪唑基)吲哚类化合物在杀灭农作物致病菌中的应用。
所述的农作物致病菌为番茄早疫病菌、草莓灰霉病菌、苹果斑点病菌、水稻纹枯病菌、小麦赤霉病菌、黄瓜炭疽病菌，优选为水稻纹枯病菌、草莓灰霉病菌、黄瓜炭疽病菌。
具体实施方式
实施例1
3-(1-丙基-1-氢-咪唑-5-基)-1氢-吲哚(化合物3a)
Figure BDA0002731380150000031
参照发明专利申请CN 111333634 A实施例1合成吲哚-3-甲醛(化合物2)，取100mL圆底烧瓶，加入吲哚-3-甲醛(4mmoL,0.58g)，加入无水甲醇10mL、无水乙二醇二甲醚10mL，使吲哚-3-甲醛溶解。再加入正丙胺CH3CH2CH2NH2(6mmol)，于20℃下反应生成亚胺。待反应进度不发生变化后，再加入TosMIC(6mmol,1.17g)及K2CO3(6mmol,0.83g)，在45-50℃与亚胺发生反应生成咪唑环。用TLC监测反应进程。反应完成后，用旋转蒸发仪脱去溶剂，加入水和二氯甲烷，用二氯甲烷萃取后合并有机相，再经过水洗和饱和食盐水洗涤后，加入无水硫酸钠干燥。使用干法上样以硅胶柱层析法纯化产物，洗脱剂为石油醚/乙酸乙酯/甲醇体积比＝40:20:1，纯化得到化合物3a。
黄色固体，产率：94％。Mp:128.9-130.1℃.1H NMR(400MHz,MeOD)δ7.68(s,1H),7.56-7.51(m,2H),7.49(s,1H),7.22-7.16(m,1H),7.13-7.07(m,1H),7.03(d,J＝0.6Hz,1H),4.01(t,J＝7.2Hz,2H),1.64(dd,J＝14.6,7.3Hz,2H),0.78(t,J＝7.4Hz,3H).13C NMR(101MHz,DMSO)δ137.81,136.16,127.30,126.64,126.03,124.24,121.77,119.67,118.94,111.93,103.98,46.22,23.60,10.91.HR-MS(ESI):m/z calcd for C14H15N3([M+H]+)226.13387,found226.13428.
实施例2
3-(1-丁基-1-氢-咪唑-5-基)-1氢-吲哚(化合物3b)
在实施例1的基础上，将正丙胺替换为正丁胺，制得化合物3b。
白色晶体；产率：84％。Mp:110.1-111.9℃.1H NMR(400MHz,MeOD)δ7.77(s,1H),7.47-7.43(m,2H),7.36(s,1H),7.19(t,J＝7.6Hz,1H),7.09(t,J＝7.5Hz,1H),7.00(s,1H),4.02(td,J＝7.3,4.2Hz,2H),1.62-1.53(m,2H),1.18(dd,J＝14.7,7.2Hz,2H),0.78(dd,J＝8.4,6.4Hz,3H).13C NMR(101MHz,DMSO)δ138.05,136.43,127.63,126.92,126.30,124.52,122.05,119.94,119.23,112.19,104.31,44.58,32.63,19.49,13.70.HR-MS(ESI):m/z calcd for C15H17N3([M+H]+)240.14952,found 240.15034.
实施例3
3-(1-环己基-1-氢-咪唑-5-基)-1氢-吲哚(化合物3c)
在实施例1的基础上，将正丙胺替换为环己基胺，制得化合物3c。
淡黄色固体；产率：49％。Mp:159.4-160.5℃.1H NMR(400MHz,MeOD)δ7.87(s,1H),7.42(dd,J＝23.7,8.0Hz,2H),7.32(s,1H),7.22–7.16(m,1H),7.08(t,J＝7.4Hz,1H),6.95(s,1H),3.97(dd,J＝15.8,7.3Hz,1H),2.02(d,J＝11.3Hz,2H),1.86–1.57(m,5H),1.23(dd,J＝20.9,11.3Hz,3H).13C NMR(101MHz,MeOD)δ137.67,135.61,128.55,127.52,127.50,125.76,122.97,120.78,119.38,112.54,104.77,55.91,35.41,26.60,26.03.HR-MS(ESI):m/z calcd for C17H19N3([M+H]+)266.16517,found 266.16656.
实施例4
3-(1-苄基-1-氢-咪唑-5-基)-1氢-吲哚(化合物3d)
在实施例1的基础上，将正丙胺替换为苄胺，制得化合物3d。
淡黄色晶体；产率：44％。Mp:136.5-137.6℃.1H NMR(400MHz,MeOD)δ7.81(s,1H),7.47(d,J＝8.0Hz,1H),7.42(d,J＝8.1Hz,1H),7.25-7.15(m,4H),7.11-7.04(m,3H),6.97(d,J＝7.3Hz,2H),5.22(d,J＝2.5Hz,2H).13C NMR(101MHz,DMSO)δ138.44,138.24,136.06,128.73,127.43,126.55,126.44,126.42,123.92,121.88,119.76,119.04,111.90,103.74,47.83.HR-MS(ESI):m/z calcd for C18H15N3([M+H]+)274.13387,found 274.13574.
实施例5
3-(1-对甲基苄基-1-氢-咪唑-5-基)-1氢-吲哚(化合物3e)
在实施例1的基础上，将正丙胺替换为对甲基苄胺，制得化合物3e。
淡黄色晶体；产率：57％。Mp:169.2-170.3℃.1H NMR(400MHz,MeOD)δ7.76(s,1H),7.43(dd,J＝19.1,8.0Hz,2H),7.16(t,J＝7.4Hz,1H),7.07(dd,J＝13.6,5.3Hz,4H),6.85(d,J＝7.9Hz,2H),4.88(s,3H),2.26(s,3H).13C NMR(101MHz,DMSO)δ138.36,136.62,136.08,135.17,129.30,127.34,126.54,126.48,126.41,123.91,121.88,119.77,119.07,111.92,103.80,47.65,20.73.HR-MS(ESI):m/z calcd for C19H17N3([M+H]+)288.14952,found 288.14959.
实施例6
3-(1-对甲氧基苄基-1-氢-咪唑-5-基)-1氢-吲哚(化合物3f)
在实施例1的基础上，将正丙胺替换为对甲氧基苄胺，制得化合物3f。
淡黄色固体；产率：50％。Mp:150.1-152.0℃.1H NMR(400MHz,MeOD)δ7.76(d,J＝0.7Hz,1H),7.44(dd,J＝11.9,8.0Hz,2H),7.20–7.15(m,1H),7.13(s,1H),7.10–7.05(m,2H),6.90(d,J＝8.7Hz,2H),6.82–6.75(m,2H),5.13(s,2H),4.89(s,3H).13C NMR(101MHz,DMSO)δ158.83,138.44,136.35,130.17,128.25,127.62,126.72,126.69,124.25,122.11,120.00,119.31,114.31,112.16,104.08,55.32,47.64.HR-MS(ESI):m/z calcd forC19H17N3O([M+H]+)304.14444,found 304.14416.
实施例7
3-(1-对氟基苄基-1-氢-咪唑-5-基)-1氢-吲哚(化合物3g)
在实施例1的基础上，将正丙胺替换为对氟基苄胺，制得化合物3g。
白色固体；产率：43％。Mp:182.1-182.8℃.1H NMR(400MHz,MeOD)δ7.82(s,1H),7.44–7.40(m,2H),7.17(t,J＝7.5Hz,1H),7.12(s,1H),7.09–7.04(m,2H),6.94(d,J＝7.0Hz,4H),5.19(s,2H).13C NMR(101MHz,DMSO)δ161.34(d,JC-F＝244.2Hz,1C),138.25,135.99,134.22,134.19,128.56,128.48,127.50,126.35,123.98,121.77,119.66,118.89,115.50,115.29,111.81,103.57,47.11.HR-MS(ESI):m/z calcd for C18H14FN3([M+H]+)292.12445,found292.12442.
实施例8
3-(4-氯-1-丙基-1-氢-咪唑-5-基)-1氢-吲哚(化合物4a)
Figure BDA0002731380150000051
将化合物3a(1mmol)、四氢呋喃10mL、四氯化碳10mL加入到50mL圆底烧瓶中，于45-50℃下搅拌，待底物溶解后，称取NCS(1.1mmoL，0.15g)，分批加入，TLC监测反应进程，反应结束减压脱去溶剂，加入水和二氯甲烷，二氯甲烷萃取后合并有机相，再依次用水和饱和食盐水洗涤，加入无水硫酸钠干燥。使用干法上样以硅胶柱层析法纯化产物，洗脱剂为石油醚/乙酸乙酯/甲醇体积比＝40:20:1，得化合物4a。
白色晶体；产率：43％。Mp:144.9-146.1℃.1H NMR(400MHz,Acetone)δ10.75(s,1H),7.67(s,1H),7.56–7.49(m,2H),7.40(d,J＝7.9Hz,1H),7.20(t,J＝7.5Hz,1H),7.10(t,J＝7.4Hz,1H),3.92(t,J＝7.2Hz,2H),1.56(dd,J＝14.5,7.3Hz,2H),0.73(t,J＝7.4Hz,3H).13C NMR(101MHz,Acetone)δ137.23,136.42,128.79,127.87,126.79,122.74,121.96,120.59,119.88,112.63,103.03,48.18,24.39,10.91.HR-MS(ESI):m/z calcd forC14H14ClN3([M+H]+)260.09490,found 260.09637.
实施例9
3-(4-氯-1-丁基-1-氢-咪唑-5-基)-1氢-吲哚(化合物4b)
在实施例8的基础上，将化合物3a替换为化合物3b，制得化合物4b。
白色晶体；产率：94％。Mp:171.5-173.3℃.1H NMR(400MHz,DMSO)δ11.54(s,1H),7.81(d,J＝15.4Hz,1H),7.57-7.53(m,1H),7.47(d,J＝8.1Hz,1H),7.29(dd,J＝7.7,4.7Hz,1H),7.16(t,J＝7.4Hz,1H),7.06(t,J＝7.4Hz,1H),3.86(t,J＝7.1Hz,2H),1.42(dq,J＝14.6,7.2Hz,2H),1.09-1.01(m,2H),0.67(td,J＝7.3,3.5Hz,3H).13C NMR(101MHz,Acetone)δ137.23,136.36,128.78,127.89,126.80,122.75,121.91,120.59,119.90,112.62,103.11,46.29,33.20,19.95,13.49.HR-MS(ESI):m/z calcd for C15H16ClN3([M+H]+)274.11055,found274.11007.
实施例10
3-(4-氯-1-环己基-1-氢-咪唑-5-基)-1氢-吲哚(化合物4c)
在实施例8的基础上，将化合物3a替换为化合物3c，制得化合物4c。
黄色固体；产率：67％。Mp:190.3-192.2℃.1H NMR(400MHz,Acetone)δ10.76(s,1H),7.77(s,1H),7.56–7.50(m,2H),7.38(d,J＝7.9Hz,1H),7.23–7.17(m,1H),7.14–7.07(m,1H),3.94–3.84(m,1H),2.03–1.96(m,2H),1.74(dd,J＝16.3,7.4Hz,4H),1.62–1.57(m,1H),1.23–1.11(m,3H).13C NMR(101MHz,MeOD)δ136.43,132.91,127.03,126.92,126.03,121.86,121.42,119.70,118.34,111.53,101.23,55.83,33.81,25.26,24.70.HR-MS(ESI):m/z calcd forC17H18ClN3([M+H]+)300.12620,found 300.12736.
实施例11
3-(4-氯-1-苄基-1-氢-咪唑-5-基)-1氢-吲哚(化合物4d)
在实施例8的基础上，将化合物3a替换为化合物3d，制得化合物4d。
淡黄色固体；产率：58％。Mp:179.2-180.4℃.1H NMR(400MHz,Acetone)δ10.68(s,1H),7.74(s,1H),7.50(d,J＝8.2Hz,1H),7.41(d,J＝7.9Hz,1H),7.30(d,J＝2.6Hz,1H),7.27-7.16(m,4H),7.09(t,J＝7.2Hz,1H),7.01-6.98(m,2H),5.19(s,2H).13C NMR(101MHz,Acetone)δ138.20,137.14,136.81,129.29,128.97,128.29,127.78,127.58,126.91,122.74,122.47,120.60,119.99,112.58,102.71,49.86.HR-MS(ESI):m/z calcdforC18H14ClN3([M+H]+)308.09490,found 308.09821.
实施例12
3-(4-氯-1-对甲基苄基-1-氢-咪唑-5-基)-1氢-吲哚(化合物4e)
在实施例8的基础上，将化合物3a替换为化合物3e，制得化合物4e。
淡黄色固体；产率：40％。Mp:190.8-192.8℃.1H NMR(400MHz,MeOD)δ7.76(s,1H),7.44(d,J＝8.2Hz,1H),7.29(d,J＝8.0Hz,1H),7.18(t,J＝7.6Hz,1H),7.13(s,1H),7.07(d,J＝7.2Hz,1H),7.02(d,J＝7.9Hz,2H),6.80(d,J＝7.9Hz,2H),5.04(s,2H),2.25(s,3H).13C NMR(101MHz,DMSO)δ136.79,136.51,135.98,134.32,129.16,127.11,126.71,126.43,121.74,121.54,119.70,119.04,112.06,100.94,99.60 48.54,20.66.HR-MS(ESI):m/z calcd for C19H16ClN3([M+H]+)322.11055,found 322.11353.
实施例13
3-(4-氯-1-对甲氧基苄基-1-氢-咪唑-5-基)-1氢-吲哚(化合物4f)
在实施例8的基础上，将化合物3a替换为化合物3f，制得化合物4f。
淡黄色固体；产率：50％。Mp:176.3-177.6℃.1H NMR(400MHz,MeOD)δ7.78(s,1H),7.45(d,J＝8.2Hz,1H),7.27(d,J＝8.0Hz,1H),7.21–7.14(m,2H),7.06(t,J＝7.5Hz,1H),6.82(d,J＝8.6Hz,2H),6.73(d,J＝8.7Hz,2H),5.01(s,2H),3.71(s,3H).13C NMR(101MHz,DMSO)δ158.69,136.35,135.99,129.13,128.32,127.13,126.48,126.45,121.75,121.44,119.71,119.04,113.99,112.06,101.01,55.11,48.32.HR-MS(ESI):m/z calcd forC19H16ClN3O([M+H]+)338.10547,found 338.10842.
实施例14
3-(4-氯-1-对氟基苄基-1-氢-咪唑-5-基)-1氢-吲哚(化合物4g)
在实施例8的基础上，将化合物3a替换为化合物3g，制得化合物4g。
白色固体；产率：43％。Mp:174.7-176.5℃.1H NMR(400MHz,DMSO)δ11.52(s,1H),7.90(s,1H),7.45(s,1H),7.35(s,1H),7.27(s,1H),7.15(t,J＝6.9Hz,1H),7.03(t,J＝8.0Hz,3H),6.93(s,2H),5.12(s,2H).13C NMR(101MHz,DMSO)δ161.47(d,JC-F＝243.7Hz,1C),136.58,135.97,133.46,128.94,128.86,127.38,126.51,126.44,121.77,121.47,119.72,118.94,115.49,115.28,112.06,100.84,48.12.HR-MS(ESI):m/z calcd forC18H13ClFN3([M+H]+)326.08548,found 326.08503.
实施例15
3-(4-溴-1-丙基-1-氢-咪唑-5-基)-1氢-吲哚(化合物5a)
Figure BDA0002731380150000081
将化合物3a(1mmol)、四氢呋喃10mL、四氯化碳10mL，加入到50mL圆底烧瓶中，于45-50℃下搅拌。待底物溶解后，称取NBS(1.1mmoL，0.20g)，分批加入，TLC监测反应进程，反应结束减压脱去溶剂，加入水和二氯甲烷，二氯甲烷萃取后合并有机相，再分别用水和饱和食盐水洗涤，加入无水硫酸钠干燥。使用干法上样以硅胶柱层析法纯化产物，洗脱剂为石油醚/乙酸乙酯/甲醇体积比＝40:20:1，得化合物5a。
淡黄色晶体；产率：55％。Mp:145.3-146.4℃.1H NMR(400MHz,Acetone)δ10.75(s,1H),7.71(s,1H),7.53(dd,J＝5.3,2.7Hz,2H),7.39(d,J＝7.9Hz,1H),7.24-7.16(m,1H),7.13-7.07(m,1H),3.93(t,J＝7.2Hz,2H),1.61-1.50(m,2H),0.72(t,J＝7.4Hz,3H).13CNMR(101MHz,Acetone)δ137.79,137.20,127.82,126.97,124.87,122.71,120.57,119.91,116.47,112.63,103.41,48.23,24.41,10.90.HR-MS(ESI):m/z calcd for C14H14BrN3([M+H]+)304.04439,found 304.04427.
实施例16
3-(4-溴-1-丁基-1-氢-咪唑-5-基)-1氢-吲哚(化合物5b)
在实施例15的基础上，将化合物3a替换为化合物3b，制得化合物5b。
白色晶体；产率：63％。Mp:176.1-178.0℃.1H NMR(400MHz,DMSO)δ11.53(s,1H),7.82(s,1H),7.54(d,J＝2.5Hz,1H),7.47(d,J＝8.1Hz,1H),7.28(d,J＝7.9Hz,1H),7.16(t,J＝7.5Hz,1H),7.05(t,J＝7.5Hz,1H),3.86(t,J＝7.1Hz,2H),1.45-1.37(m,2H),1.05(dd,J＝14.8,7.4Hz,2H),0.66(t,J＝7.4Hz,3H).13C NMR(101MHz,Acetone)δ137.34,136.84,127.48,126.61,124.46,122.35,120.19,119.56,116.13,112.25,103.15,45.97,32.84,19.56,13.10.HR-MS(ESI):m/z calcd for C15H16BrN3([M+H]+)318.06004,found318.06182.
实施例17
3-(4-溴-1-环己基-1-氢-咪唑-5-基)-1氢-吲哚(化合物5c)
在实施例15的基础上，将化合物3a替换为化合物3c，制得化合物5c。
黄色固体；产率：47％。Mp:197.6-199.1℃.1H NMR(400MHz,Acetone)δ10.75(s,1H),7.82(s,1H),7.53(t,J＝5.4Hz,2H),7.37(d,J＝7.9Hz,1H),7.20(m,1H),7.11(m,1H),3.89(m,1H),1.99(m,2H),1.76(d,J＝10.2Hz,4H),1.58(d,J＝9.5Hz,1H),1.18(dt,J＝20.7,9.1Hz,3H).13C NMR(101MHz,MeOD)δ136.42,134.38,127.02,126.19,124.42,121.83,119.69,118.37,114.25,111.52,101.72,55.99,33.91,25.27,24.70.HR-MS(ESI):m/zcalcd for C17H18BrN3([M+H]+)344.07569,found 344.07844.
实施例18
3-(4-溴-1-苄基-1-氢-咪唑-5-基)-1氢-吲哚(化合物5d)
在实施例15的基础上，将化合物3a替换为化合物3d，制得化合物5d。
淡黄色晶体；产率：58％。Mp:204.6-206.0℃.1H NMR(400MHz,MeOD)δ7.83(s,1H),7.43(d,J＝8.2Hz,1H),7.28(d,J＝8.0Hz,1H),7.22-7.15(m,4H),7.13(s,1H),7.05(t,J＝7.5Hz,1H),6.90(dd,J＝6.4,2.6Hz,2H),5.10(s,2H).13C NMR(101MHz,DMSO)δ137.96,137.34,135.99,128.71,128.59,127.57,126.71,126.64,126.44,126.05,124.48,121.74,119.71,119.10,115.37,112.06,101.37,48.81.HR-MS(ESI):m/z calcd for C18H14BrN3([M+H]+)352.04439,found 352.04771.
实施例19
3-(4-溴-1-对甲基苄基-1-氢-咪唑-5-基)-1氢-吲哚(化合物5e)
在实施例15的基础上，将化合物3a替换为化合物3e，制得化合物5e。
淡黄色晶体；产率：64％。Mp:196.9-198.1℃.1H NMR(400MHz,MeOD)δ7.79(s,1H),7.44(d,J＝8.2Hz,1H),7.28(d,J＝8.0Hz,1H),7.17(s,1H),7.14(s,1H),7.05(s,1H),7.01(d,J＝7.8Hz,2H),6.79(d,J＝7.9Hz,2H),5.04(s,2H),2.24(s,3H).13C NMR(101MHz,DMSO)δ138.22,137.18,136.37,134.70,129.53,127.15,127.02,126.81,124.79,122.11,120.08,119.51,115.65,112.45,101.79,48.98,21.06.HR-MS(ESI):m/z calcd forC19H16BrN3([M+H]+)366.06004,found 366.06302.
实施例20
3-(4-溴-1-对甲氧基苄基-1-氢-咪唑-5-基)-1氢-吲哚(化合物5f)
在实施例15的基础上，将化合物3a替换为化合物3f，制得化合物5f。
淡黄色晶体；产率：56％。Mp:187.5-189.1℃.1H NMR(400MHz,MeOD)δ7.74(s,1H),7.45(d,J＝8.2Hz,1H),7.29(d,J＝8.0Hz,1H),7.21–7.15(m,2H),7.06(t,J＝7.5Hz,1H),6.84(d,J＝8.6Hz,2H),6.74(d,J＝8.7Hz,2H),5.02(s,2H),3.71(s,3H).13C NMR(101MHz,DMSO)δ158.70,137.69,136.00,129.12,128.37,126.68,126.45,124.32,121.73,119.71,119.11,115.28,113.97,112.08,101.46,55.11(s),48.38(s).HR-MS(ESI):m/z calcd forC19H16BrN3O([M+H]+)382.05495,found 382.05835.
实施例21
3-(4-溴-1-对氟基苄基-1-氢-咪唑-5-基)-1氢-吲哚(化合物5g)
在实施例15的基础上，将化合物3a替换为化合物3g，制得化合物5g。
白色晶体；产率：49％。Mp:198.5-199.5℃.1H NMR(400MHz,Acetone)δ10.69(s,1H),7.80(s,1H),7.50(d,J＝8.2Hz,1H),7.35(dd,J＝10.0,5.3Hz,2H),7.22-7.15(m,1H),7.09(dd,J＝11.1,3.9Hz,1H),7.04-6.93(m,4H),5.19(s,2H).13C NMR(101MHz,DMSO)δ161.71(d,JC-F＝243.6 Hz,1C),138.15,136.22,133.68,129.23,129.14,126.94,126.68,124.59,121.98,119.95,119.26,115.77,115.71,115.49,112.31,101.56,48.43.HR-MS(ESI):m/z calcd for C18H13BrFN3([M+H]+)370.03496,found 370.03449.
实施例22
3-(1-异丁基-1-氢-咪唑-5-基)-1氢-吲哚(化合物A-1)
在实施例1的基础上，将正丙胺替换为异丁胺，制得化合物A-1。
白色固体；产率：30％。m.p.118.1–119.2℃.1H NMR(400MHz,Acetone-d6)δ(ppm)＝10.66(s,1H),7.64(s,1H),7.56–7.46(m,3H),7.18(t,J＝7.6Hz,1H),7.10(t,J＝7.5Hz,1H),7.03(s,1H),3.88(d,J＝7.4Hz,2H),1.92–1.80(m,1H),0.74(d,J＝6.7Hz,6H).13C NMR(101MHz,DMSO-d6)δ(ppm)＝138.7,136.4,127.8,127.0,126.5,124.5,122.1,120.0,119.3,112.2,104.5,52.3,29.2,19.9.HR-MS(ESI):m/z calcd for C15H17N3([M+H]+)240.1495,Found 240.1490.
实施例23
3-(1-(2-甲氧基乙基)-1-氢-咪唑-5-基)-1氢-吲哚(化合物A-2)
在实施例1的基础上，将正丙胺替换为2-甲氧基乙胺，制得化合物A-2。
鲜黄色固体；产率：71％。m.p.112.9–114.5℃.1H NMR(400MHz,DMSO-d6)δ(ppm)＝11.55(s,1H),7.79(d,J＝1.1Hz,1H),7.58(d,J＝2.6Hz,1H),7.54(d,J＝7.9Hz,1H),7.50(d,J＝8.0Hz,1H),7.21–7.15(m,1H),7.12–7.06(m,2H),4.15(t,J＝5.4Hz,2H),3.50(t,J＝5.4Hz,2H),3.18(s,3H).13C NMR(101MHz,DMSO-d6)δ(ppm)＝138.4,136.6,127.5,127.0,126.6,125.0,122.2,120.1,119.3,112.3,104.1,71.4,58.5,44.7.HR-MS(ESI):m/z calcdfor C14H15N3O([M+H]+)242.1288,Found 242.1289.
实施例24
3-(1-(3-甲基苄基)-1-氢-咪唑-5-基)-1氢-吲哚(化合物A-3)
在实施例1的基础上，将正丙胺替换为3-甲基苄胺，制得化合物A-3。
黄色固体；产率：39％。m.p.145.9–146.6℃.1H NMR(400MHz,Acetone-d6)δ(ppm)＝10.84(s,1H),7.77(s,1H),7.61(d,J＝7.9Hz,1H),7.50(d,J＝8.1Hz,1H),7.28(d,J＝2.6Hz,1H),7.22–7.16(m,3H),7.15–7.08(m,2H),7.05(d,J＝7.6Hz,1H),6.89–6.82(m,2H),5.27(s,2H),2.22(s,3H).13C NMR(101MHz,DMSO-d6)δ(ppm)＝138.7,138.5,138.2,136.4,129.0,128.4,127.7,127.4,126.9,126.8,124.3,123.9,122.2,120.1,119.4,112.2,104.1,48.1,21.4.HR-MS(ESI):m/z calcd for C19H17N3([M+H]+)288.1495,Found288.1489.
实施例25
3-(1-(2-甲基苄基)-1-氢-咪唑-5-基)-1氢-吲哚(化合物A-4)
在实施例1的基础上，将正丙胺替换为2-甲基苄胺，制得化合物A-4。
黄色固体，产率：87％。m.p.176.7–178.1℃.1H NMR(400MHz,DMSO-d6)δ(ppm)＝11.31(s,1H),7.70(d,J＝1.2Hz,1H),7.59(d,J＝7.9Hz,1H),7.41(d,J＝8.0Hz,1H),7.19–7.16(m,4H),7.15–7.11(m,2H),7.11–7.06(m,2H),5.26(s,2H),2.17(s,3H).13C NMR(101MHz,DMSO-d6)δ(ppm)＝138.6,136.7,136.4,135.2,130.5,127.7,127.6,127.2,126.7,126.7,126.1,123.9,122.2,120.1,119.4,112.2,104.1,46.5,18.9.HR-MS(ESI):m/z calcd for C19H17N3([M+H]+)288.1495,Found 288.1502.
实施例26
3-(1-(3-甲氧基苄基)-1-氢-咪唑-5-基)-1氢-吲哚(化合物A-5)
在实施例1的基础上，将正丙胺替换为3-甲氧基苄胺，制得化合物A-5。
白色固体；产率：80％。m.p.152.6–154.5℃.1H NMR(400MHz,Acetone-d6)δ(ppm)＝10.60(s,1H),7.76(d,J＝1.2Hz,1H),7.62(dd,J＝7.9,1.0Hz,1H),7.51–7.46(m,1H),7.28(d,J＝2.6Hz,1H),7.23–7.08(m,4H),6.84–6.76(m,1H),6.65–6.61(m,1H),6.59(t,J＝2.0Hz,1H),5.30(s,2H),3.67(s,3H).13C NMR(101MHz,DMSO-d6)δ(ppm)＝159.8,140.2,138.8,136.4,130.2,127.7,126.8,126.8,124.3,122.2,120.1,119.4,118.9,113.2,112.5,112.2,104.1,55.3,48.1.HR-MS(ESI):m/z calcd for C19H17N3O([M+H]+)304.1444,Found 304.1448.
实施例27
3-(1-(2-甲氧基苄基)-1-氢-咪唑-5-基)-1氢-吲哚(化合物A-6)
在实施例1的基础上，将正丙胺替换为2-甲氧基苄胺，制得化合物A-6。
白色固体；产率：66％。m.p.170.5–172.0℃.1H NMR(400MHz,DMSO-d6)δ(ppm)＝11.36(s,1H),7.76(s,1H),7.57(d,J＝7.9Hz,1H),7.44(d,J＝8.0Hz,1H),7.29–7.20(m,2H),7.20–7.13(m,2H),7.07(t,J＝7.5Hz,1H),6.98(d,J＝8.2Hz,1H),6.83(t,J＝7.5Hz,1H),6.54(dd,J＝7.5,1.7Hz,1H),5.21(s,2H),3.75(s,3H).13C NMR(101MHz,DMSO-d6)δ(ppm)＝156.4,138.8,136.4,129.3,127.6,127.4,127.0,126.9,126.2,124.2,122.2,120.9,120.1,119.4,112.2,111.1,104.1,55.8,43.8.HR-MS(ESI):m/z calcd forC19H17N3O([M+H]+)304.1444,Found 304.1459.
实施例28
3-(1-(3-氟基苄基)-1-氢-咪唑-5-基)-1氢-吲哚(化合物A-7)
在实施例1的基础上，将正丙胺替换为3-氟基苄胺，制得化合物A-7。
鲜黄色固体，产率：34％。m.p.156.4–157.9℃.1H NMR(400MHz,Acetone-d6)δ(ppm)＝10.93(s,1H),7.85(s,1H),7.61(d,J＝7.9Hz,1H),7.50(d,J＝8.1Hz,1H),7.34–7.28(m,2H),7.24–7.17(m,2H),7.12(t,J＝7.5Hz,1H),7.03–6.96(m,1H),6.87(d,J＝7.7Hz,1H),6.79(d,J＝10.0Hz,1H),5.37(s,2H).13C NMR(101MHz,Acetone-d6)δ(ppm)＝164.1,161.7,141.1(d,J＝7.2Hz),138.3,136.4,130.6(d,J＝8.4Hz),127.9,127.0(d,J＝14.8Hz),124.0,122.4(d,J＝2.9Hz),122.1,119.9,119.0,114.1(d,J＝21.2Hz),113.4(d,J＝22.4Hz),111.8,104.0,47.6(d,J＝2.0Hz).19F NMR(376MHz,Acetone-d6)δ(ppm)＝-114.2.HR-MS(ESI):m/z calcd for C18H14FN3([M+H]+)292.1245,Found 292.1258.
实施例29
3-(1-(2-氟基苄基)-1-氢-咪唑-5-基)-1氢-吲哚(化合物A-8)
在实施例1的基础上，将正丙胺替换为2-氟基苄胺，制得化合物A-8。
黄色固体；产率：45％。m.p.150.8–151.5℃.1H NMR(400MHz,DMSO-d6)δ(ppm)＝11.37(s,1H),7.81(d,J＝1.0Hz,1H),7.51(d,J＝7.9Hz,1H),7.42(d,J＝8.1Hz,1H),7.34–7.25(m,2H),7.19–7.12(m,3H),7.10–7.02(m,2H),6.74–6.68(m,1H),5.34(s,2H).13C NMR(101MHz,DMSO-d6)δ(ppm)＝161.0,158.6,138.8,136.4,130.1(d,J＝8.1Hz),128.9(d,J＝4.0Hz),127.9,126.9(d,J＝9.0Hz),125.3(d,J＝14.4Hz),125.1(d,J＝3.5Hz),124.5,122.2,120.1,119.3,115.7(d,J＝20.7Hz),112.3,103.9,42.5(d,J＝4.8Hz).19F NMR(376MHz,DMSO-d6)δ(ppm)＝-118.4(d,J＝9.3Hz).HR-MS(ESI):m/z calcd for C18H14FN3([M+H]+)292.1245,Found 292.1239.
实施例30
3-(1-(4-氯基苄基)-1-氢-咪唑-5-基)-1氢-吲哚(化合物A-9)
在实施例1的基础上，将正丙胺替换为4-氯基苄胺，制得化合物A-9。
灰色固体；产率：30％。m.p.204.7–206.5℃.1H NMR(400MHz,DMSO-d6)δ(ppm)＝11.39(s,1H),7.86(s,1H),7.54(d,J＝7.9Hz,1H),7.44(d,J＝8.1Hz,1H),7.32(d,J＝8.3Hz,2H),7.30(d,J＝2.7Hz,1H),7.16(q,J＝7.6,6.0Hz,2H),7.06(t,J＝7.5Hz,1H),6.97(d,J＝8.1Hz,2H),5.30(s,2H).13C NMR(101MHz,DMSO-d6)δ(ppm)＝138.8,137.6,136.4,132.4,129.0,128.7,127.9,126.9,126.8,124.4,122.2,120.1,119.3,112.3,103.9,47.6.HR-MS(ESI):m/z calcd for C18H14ClN3([M+H]+)308.0949,Found 308.0964.
实施例31
3-(1-(4-溴基苄基)-1-氢-咪唑-5-基)-1氢-吲哚(化合物A-10)
在实施例1的基础上，将正丙胺替换为4-溴基苄胺，制得化合物A-10。
鲜黄色固体，产率：38％。m.p.211.5–213.0℃.1H NMR(400MHz,DMSO-d6)δ(ppm)＝11.34(s,1H),7.84(s,1H),7.52(d,J＝8.1Hz,1H),7.46(d,J＝7.9Hz,2H),7.42(d,J＝8.6Hz,1H),7.28(s,1H),7.14(d,J＝5.2Hz,2H),7.06(d,J＝7.5Hz,1H),6.90(d,J＝8.0Hz,2H),5.28(s,2H).13C NMR(101MHz,DMSO-d6)δ(ppm)＝138.8,138.0,136.4,132.0,129.0,128.0,126.8,124.4,122.3,120.9,120.1,119.4,112.3,103.9,47.7.HR-MS(ESI):m/zcalcd for C18H14BrN3([M+H]+)352.0444,Found 352.0440.
实施例32
3-(1-(4-三氟甲基苄基)-1-氢-咪唑-5-基)-1氢-吲哚(化合物A-11)
在实施例1的基础上，将正丙胺替换为4-三氟甲基苄胺，制得化合物A-11。
鲜黄色固体，产率：25％。m.p.203.5–204.5℃.1H NMR(400MHz,DMSO-d6)δ(ppm)＝11.34(s,1H),7.90(d,J＝1.1Hz,1H),7.64(d,J＝8.1Hz,2H),7.52(d,J＝7.9Hz,1H),7.41(d,J＝8.1Hz,1H),7.27(d,J＝2.5Hz,1H),7.17–7.12(m,4H),7.08–7.02(m,1H),5.42(s,2H).13C NMR(101MHz,DMSO-d6)δ(ppm)＝143.3,138.9,136.4,127.9,127.4,126.9,126.7,126.0,126.0,125.9,124.4,122.3,120.1,119.3,112.3,103.8,47.8.19F NMR(376MHz,DMSO-d6)δ(ppm)＝-60.9(s,3F).HR-MS(ESI):m/z calcd for C19H14F3N3([M+H]+)342.1213,Found 342.1216.
实施例33
3-(1-(吡啶-3-基甲基)-1-氢-咪唑-5-基)-1氢-吲哚(化合物A-12)
在实施例1的基础上，将正丙胺替换为吡啶-3-基甲胺制得化合物A-12。
鲜黄色固体，产率：59％。m.p.118.8–120.5℃.1H NMR(400MHz,DMSO-d6)δ(ppm)＝11.43(s,1H),8.39(dd,J＝4.7,1.7Hz,1H),8.19(d,J＝2.2Hz,1H),7.91(d,J＝1.2Hz,1H),7.51(d,J＝7.9Hz,1H),7.44(d,J＝8.1Hz,1H),7.40(d,J＝2.6Hz,1H),7.33–7.29(m,1H),7.27–7.23(m,1H),7.19–7.12(m,2H),7.08–7.03(m,1H),5.36(s,2H).13C NMR(101MHz,DMSO-d6)δ(ppm)＝149.0,148.4,138.8,136.4,134.8,133.9,128.1,126.8,126.7,124.6,124.1,122.2,120.1,119.3,112.3,103.8,46.0.HR-MS(ESI):m/z calcd for C17H14N4([M+H]+)275.1291,Found 275.1283.
实施例34
3-(4-氯-1-异丁基-1-氢-咪唑-5-基)-1氢-吲哚(化合物A-13)
在实施例8的基础上，将正丙胺替换为异丁胺。制得化合物A-13。
鲜黄色固体，产率：56％。m.p.168.7–169.9℃.1H NMR(400MHz,DMSO-d6)δ(ppm)＝11.56(s,1H),7.77(s,1H),7.56(d,J＝2.7Hz,1H),7.48(d,J＝8.1Hz,1H),7.30(d,J＝7.9Hz,1H),7.16(t,J＝7.5Hz,1H),7.06(t,J＝7.5Hz,1H),3.72(d,J＝7.4Hz,2H),1.72–1.59(m,1H),0.62(d,J＝6.7Hz,6H).13C NMR(101MHz,DMSO-d6)δ(ppm)＝137.0,136.4,127.5,126.9,126.8,122.1,121.6,120.1,119.3,112.5,101.7,53.1,28.9,19.8.HR-MS(ESI):m/z calcd for C15H16ClN3([M+H]+)274.1106,Found 274.1108.
实施例35
3-(4-氯-1-(2-甲氧基乙基)-1-氢-咪唑-5-基)-1氢-吲哚(化合物A-14)
在实施例8的基础上，将正丙胺替换为2-甲氧基乙胺，制得化合物A-14。
鲜黄色固体，产率：30％。m.p.154.6–155.9℃.1H NMR(400MHz,Acetone-d6)δ(ppm)＝10.78(s,1H),7.68(s,1H),7.57(d,J＝2.6Hz,1H),7.54(d,J＝8.4Hz,1H),7.43(d,J＝8.0Hz,1H),7.22(t,J＝7.6Hz,1H),7.12(t,J＝7.5Hz,1H),4.10(t,J＝5.3Hz,2H),3.49(t,J＝5.3Hz,2H),3.22(s,3H).13C NMR(101MHz,DMSO-d6)δ(ppm)＝136.9,136.5,127.2,127.2,126.9,122.2,121.7,120.2,119.4,112.5,101.4,70.8,58.4,45.6.HR-MS(ESI):m/zcalcd for C14H14ClN3O([M+H]+)276.0898,Found 276.0898.
实施例36
3-(4-氯-1-(3-甲基苄基)-1-氢-咪唑-5-基)-1氢-吲哚(化合物A-15)
在实施例8的基础上，将正丙胺替换为3-甲基苄胺，制得化合物A-15。
粉色固体，产率：65％。m.p.146.3–147.4℃.1H NMR(400MHz,Acetone-d6)δ(ppm)＝10.78(s,1H),7.76(s,1H),7.53(d,J＝8.1Hz,1H),7.42(d,J＝7.9Hz,1H),7.36(d,J＝2.7Hz,1H),7.24–7.18(m,1H),7.12(q,J＝7.3Hz,2H),7.03(d,J＝7.6Hz,1H),6.84–6.77(m,2H),5.15(s,2H),2.19(s,3H).13C NMR(101MHz,Acetone-d6)δ(ppm)＝138.2,137.2,136.4,136.1,128.5,128.3,128.1,127.7,127.1,126.3,124.0,122.0,121.8,119.9,119.3,111.9,101.9,49.2,20.4.HR-MS(ESI):m/z calcd for C19H16ClN3([M+H]+)322.1106,Found 322.1105.
实施例37
3-(4-氯-1-(2-甲基苄基)-1-氢-咪唑-5-基)-1氢-吲哚(化合物A-16)
在实施例8的基础上，将正丙胺替换为2-甲基苄胺，制得化合物A-16。
粉色固体，产率：54％。m.p.205.4–206.6℃.1H NMR(400MHz,Acetone-d6)δ(ppm)＝10.65(s,1H),7.58(d,J＝1.5Hz,1H),7.50(d,J＝8.1Hz,1H),7.46(d,J＝8.0Hz,1H),7.31(d,J＝2.3Hz,1H),7.23–7.08(m,5H),6.82(d,J＝7.1Hz,1H),5.18(s,2H),2.09(s,3H).13CNMR(101MHz,DMSO-d6)δ(ppm)＝137.1,136.3,135.8,135.3,130.5,127.9,127.4,126.8,126.6,126.6,126.5,122.3,122.1,120.1,119.5,112.4,101.3,47.2,18.8.HR-MS(ESI):m/z calcd for C19H16ClN3([M+H]+)322.1106,Found 322.1108.
实施例38
3-(4-氯-1-(3-甲氧基苄基)-1-氢-咪唑-5-基)-1氢-吲哚(化合物A-17)
在实施例8的基础上，将正丙胺替换为3-甲氧基苄胺，制得化合物A-17。
粉色固体，产率：38％。m.p.175.5–176.8℃.1H NMR(400MHz,Acetone-d6)δ(ppm)＝10.70(s,1H),7.77(s,1H),7.52(d,J＝8.1Hz,1H),7.43(d,J＝8.0Hz,1H),7.36(d,J＝2.7Hz,1H),7.19(dt,J＝12.5,7.7Hz,2H),7.11(t,J＝7.5Hz,1H),6.78(dd,J＝8.2,2.6Hz,1H),6.61(d,J＝7.6Hz,1H),6.53(d,J＝2.1Hz,1H),5.18(s,2H),3.63(s,3H).13C NMR(101MHz,DMSO-d6)δ(ppm)＝159.7,139.3,137.0,136.4,130.1,127.6,126.8,122.2,122.0,120.1,119.5,119.3,113.6,112.7,112.5,101.4,55.3,49.1.HR-MS(ESI):m/zcalcd for C19H16ClN3O([M+H]+)338.1055,Found 338.1053.
实施例39
3-(4-氯-1-(2-甲氧基苄基)-1-氢-咪唑-5-基)-1氢-吲哚(化合物A-18)
在实施例8的基础上，将正丙胺替换为2-甲氧基苄胺，制得化合物A-18。
白色固体，产率：63％。m.p.195.4–196.2℃.1H NMR(400MHz,Acetone-d6)δ(ppm)＝10.68(s,1H),7.65(s,1H),7.54–7.49(m,1H),7.44(dd,J＝7.9,1.0Hz,1H),7.36(d,J＝2.6Hz,1H),7.28–7.17(m,2H),7.13–7.08(m,1H),6.94(dd,J＝8.3,1.0Hz,1H),6.85–6.80(m,1H),6.71(dd,J＝7.6,1.7Hz,1H),5.12(s,2H),3.74(s,3H).13C NMR(101MHz,DMSO-d6)δ(ppm)＝156.5,137.1,136.3,129.6,127.8,127.3,126.9,126.8,125.3,122.2,122.1,120.8,120.1,119.4,112.4,111.1,101.3,55.7,44.7.HR-MS(ESI):m/z calcd forC19H16ClN3O([M+H]+)338.1055,Found 338.1050.
实施例40
3-(4-氯-1-(3-氟基苄基)-1-氢-咪唑-5-基)-1氢-吲哚(化合物A-19)
在实施例8的基础上，将正丙胺替换为3-氟基苄胺，制得化合物A-19。
粉色固体，产率：39％。m.p.183.6–184.1℃.1H NMR(400MHz,DMSO-d6)δ(ppm)＝11.55(d,J＝5.6Hz,1H),7.94(d,J＝5.9Hz,1H),7.45(t,J＝7.0Hz,1H),7.36(q,J＝2.8Hz,1H),7.30–7.22(m,2H),7.15(q,J＝6.8Hz,1H),7.03(q,J＝7.0Hz,2H),6.71(q,J＝7.9,7.3Hz,2H),5.16(d,J＝5.5Hz,2H).13C NMR(101MHz,DMSO-d6)δ(ppm)＝163.7,161.3,140.5(d,J＝7.2Hz),137.1,136.4,131.0(d,J＝8.4Hz),127.8,126.8(d,J＝8.8Hz),123.1,122.2,122.0,120.1,119.3,114.8(d,J＝20.8Hz),114.0(d,J＝22.1Hz),112.5,101.1,48.7.19F NMR(376MHz,DMSO-d6)δ(ppm)＝-113.0.HR-MS(ESI):m/z calcd for C18H13ClFN3([M+H]+)326.0855,Found 326.0857.
实施例41
3-(4-氯-1-(2-氟基苄基)-1-氢-咪唑-5-基)-1氢-吲哚(化合物A-20)
在实施例8的基础上，将正丙胺替换为2-氟基苄胺，制得化合物A-20。
粉色固体，产率：61％。m.p.177.0–178.0℃.1H NMR(400MHz,Acetone-d6)δ(ppm)＝10.70(s,1H),7.74(s,1H),7.51(d,J＝8.2Hz,1H),7.43–7.36(m,2H),7.33–7.26(m,1H),7.22–7.16(m,J＝8.2,7.0,1.2Hz,1H),7.12–7.02(m,3H),6.86–6.80(m,1H),5.26(s,2H).13C NMR(101MHz,DMSO-d6)δ(ppm)＝161.0,158.6,137.1,136.4,130.3(d,J＝8.2Hz),129.2(d,J＝3.7Hz),127.7,126.8(d,J＝2.0Hz),125.0(d,J＝3.4Hz),124.4(d,J＝14.4Hz),122.1,122.1,120.1,119.3,115.7(d,J＝20.8Hz),112.4,101.1,43.4(d,J＝4.4Hz).19F NMR(376MHz,DMSO-d6)δ(ppm)＝-118.5.HR-MS(ESI):m/z calcd forC18H13ClFN3([M+H]+)326.0855,Found 326.0859.
实施例42
3-(4-氯-1-(4-氯基苄基)-1-氢-咪唑-5-基)-1氢-吲哚(化合物A-21)
在实施例8的基础上，将正丙胺替换为4-氯基苄胺，制得化合物A-21。
黄色固体，产率：44％。m.p.198.4–199.6℃.1H NMR(400MHz,Acetone-d6)δ(ppm)＝10.69(s,1H),7.79(s,1H),7.51(d,J＝8.2Hz,1H),7.39(d,J＝8.0Hz,1H),7.34(d,J＝2.5Hz,1H),7.27(d,J＝8.4Hz,2H),7.22–7.17(m,1H),7.13–7.07(m,1H),7.00(d,J＝8.4Hz,2H),5.22(s,2H).13C NMR(101MHz,DMSO-d6)δ(ppm)＝137.1,136.7,136.3,132.6,128.9,127.8,126.9,126.8,122.2,121.9,120.1,119.3,112.5,101.2,48.5.HR-MS(ESI):m/z calcd for C18H13Cl2N3([M+H]+)342.0559,Found 342.0574.
实施例43
3-(4-氯-1-(4-溴基苄基)-1-氢-咪唑-5-基)-1氢-吲哚(化合物A-22)
在实施例8的基础上，将正丙胺替换为4-溴基苄胺，制得化合物A-22。
鲜黄色固体，产率：30％。m.p.233.8–235.1℃.1H NMR(400MHz,Acetone-d6)δ(ppm)＝10.68(s,1H),7.79(s,1H),7.51(d,J＝8.2Hz,1H),7.45–7.37(m,3H),7.34(d,J＝2.7Hz,1H),7.22–7.17(m,1H),7.12–7.07(m,1H),6.94(d,J＝8.4Hz,2H),5.20(s,2H).13C NMR(101MHz,DMSO-d6)δ(ppm)＝137.2,137.1,136.3,131.9,129.2,127.8,126.9,126.8,122.2,121.9,121.1,120.1,119.3,112.5,101.1,48.6.HR-MS(ESI):m/z calcd forC18H13BrClN3([M+H]+)386.0054,Found 386.0056.
实施例44
3-(4-氯-1-(4-三氟甲基苄基)-1-氢-咪唑-5-基)-1氢-吲哚(化合物A-23)
在实施例8的基础上，将正丙胺替换为4-三氟甲基苄胺，制得化合物A-23。
紫色固体，产率：32％。m.p.219.4–220.3℃.1H NMR(400MHz,Acetone-d6)δ(ppm)＝10.68(s,1H),7.84(s,1H),7.58(d,J＝8.1Hz,2H),7.50(d,J＝8.1Hz,1H),7.37(d,J＝8.0Hz,1H),7.34(d,J＝2.6Hz,1H),7.21–7.16(m,J＝7.9,4.7Hz,3H),7.08(t,J＝7.5Hz,1H),5.34(s,2H).13C NMR(101MHz,DMSO-d6)δ(ppm)＝142.4,137.2,136.3,128.5(q,J＝31.8Hz),127.7,126.9,126.8,125.9(d,J＝2.8Hz),125.8(d,J＝3.8Hz),122.1,122.0,121.0(q,J＝119Hz),120.1,119.3,112.4,101.1,48.7.19F NMR(376MHz,Acetone-d6)δ(ppm)＝-63.0(s,3F).HR-MS(ESI):m/z calcd for C19H13ClF3N3([M+H]+)376.0823,Found376.0829.
实施例45
3-(4-氯-1-(吡啶-3-基甲基)-1-氢-咪唑-5-基)-1氢-吲哚(化合物A-24)
在实施例8的基础上，将正丙胺替换为吡啶-3-基甲胺，制得化合物A-24。
黄色固体，产率：50％。m.p.123.8–124.8℃.1H NMR(400MHz,Acetone-d6)δ(ppm)＝10.74(s,1H),8.41(dd,J＝4.8,1.7Hz,1H),8.21(d,J＝2.3Hz,1H),7.84(s,1H),7.53–7.50(m,1H),7.42–7.37(m,2H),7.37–7.33(m,1H),7.26–7.16(m,2H),7.13–7.07(m,1H),5.29(s,2H).13C NMR(101MHz,DMSO-d6)δ(ppm)＝149.2,148.6,137.1,136.4,135.1,133.2,128.0,127.0,126.8,124.0,122.2,121.9,120.2,119.3,112.5,101.2,47.0.HR-MS(ESI):m/z calcd for C17H13ClN4([M+H]+)309.0902,Found 309.0908.
实施例46
3-(4-溴-1-异丁基-1-氢-咪唑-5-基)-1氢-吲哚(化合物A-25)
在实施例15的基础上，将正丙胺替换为异丁胺，制得化合物A-25。
黄色固体，产率：64％。m.p.133.8-135.2℃.1H NMR(400MHz,DMSO-d6)δ(ppm)＝11.56(s,1H),7.82(s,1H),7.55(d,J＝2.6Hz,1H),7.48(d,J＝8.1Hz,1H),7.29(d,J＝7.9Hz,1H),7.16(t,J＝7.5Hz,1H),7.05(t,J＝7.5Hz,1H),3.71(d,J＝7.5Hz,2H),1.69–1.57(m,1H),0.61(d,J＝6.7Hz,6H).13C NMR(101MHz,DMSO-d6)δ(ppm)＝138.4,136.4,126.9,126.9,124.5,122.1,120.1,119.4,115.6,112.5,102.1,53.2,29.0,19.8.HR-MS(ESI):m/z calcd for C15H16BrN3([M+H]+)318.0600,Found 318.0607.
实施例47
3-(4-溴-1-(2-甲氧基乙基)-1-氢-咪唑-5-基)-1氢-吲哚(化合物A-26)
在实施例15的基础上，将正丙胺替换为2-甲氧基乙胺，制得化合物A-26。
白色固体，产率:89％,m.p.139.9–140.5℃.1H NMR(400MHz,Acetone-d6)δ(ppm)＝10.77(s,1H),7.73(s,1H),7.57–7.56(m,1H),7.53(s,1H),7.42(d,J＝7.9Hz,1H),7.22(ddd,J＝8.1,6.9,1.2Hz,1H),7.15–7.10(m,1H),4.10(t,J＝5.3Hz,2H),3.47(t,J＝5.3Hz,2H),3.22(s,3H).13C NMR(101MHz,DMSO-d6)δ(ppm)＝138.3,136.5,127.3,126.9,124.5,122.1,120.1,119.5,115.4,112.5,101.8,70.8,58.4,45.7.HR-MS(ESI):m/z calcdfor C14H14BrN3O([M+H]+)320.0393,Found 320.0399.
实施例48
3-(4-溴-1-(3-甲基苄基)-1-氢-咪唑-5-基)-1氢-吲哚(化合物A-27)
在实施例15的基础上，将正丙胺替换为3-甲基苄胺，制得化合物A-27。
白色固体，产率：65％,m.p.156.0–156.6℃.1H NMR(400MHz,DMSO-d6)δ(ppm)＝11.54(s,1H),7.92(s,1H),7.47(d,J＝8.1Hz,1H),7.37(d,J＝2.6Hz,1H),7.29(d,J＝7.9Hz,1H),7.20–7.13(m,1H),7.10(t,J＝7.6Hz,1H),7.05(t,J＝7.5Hz,1H),6.99(d,J＝7.6Hz,1H),6.71(d,J＝7.7Hz,1H),6.65(s,1H),5.09(s,2H),2.12(s,3H).13C NMR(101MHz,DMSO-d6)δ(ppm)＝138.3,138.1,137.6,136.4,128.9,128.6,127.9,127.0,126.9,124.8,124.3,122.1,120.0,119.5,115.8,112.4,101.8,49.2,21.3.HR-MS(ESI):m/z calcd forC19H16BrN3([M+H]+)366.0600,Found 366.0608.
实施例49
3-(4-溴-1-(2-甲基苄基)-1-氢-咪唑-5-基)-1氢-吲哚(化合物A-28)
在实施例15的基础上，将正丙胺替换为2-甲基苄胺，制得化合物A-28。
白色固体，产率：65％,m.p.198.4–199.2℃.1H NMR(400MHz,Acetone-d6)δ(ppm)＝10.65(s,1H),7.62(s,1H),7.50(d,J＝8.1Hz,1H),7.45(d,J＝7.9Hz,1H),7.32(d,J＝2.4Hz,1H),7.23–7.07(m,5H),6.85–6.79(m,1H),5.18(s,2H),2.07(s,3H).13C NMR(101MHz,DMSO-d6)δ(ppm)＝138.4,136.3,135.8,135.3,130.5,127.9,126.8,126.7,126.6,125.1,122.1,120.1,119.5,115.8,112.4,101.7,47.3,18.8.HR-MS(ESI):m/zcalcd for C19H16BrN3([M+H]+)366.0600,Found 366.0599.
实施例50
3-(4-溴-1-(3-甲氧基苄基)-1-氢-咪唑-5-基)-1氢-吲哚(化合物A-29)
在实施例15的基础上，将正丙胺替换为3-甲氧基苄胺，制得化合物A-29。
白色固体，产率：74％。m.p.184.6–185.7℃.1H NMR(400MHz,Acetone-d6)δ(ppm)＝10.70(s,1H),7.81(s,1H),7.52(d,J＝8.2Hz,1H),7.42(d,J＝7.9Hz,1H),7.37(d,J＝2.6Hz,1H),7.23–7.14(m,2H),7.13–7.08(m,1H),6.78(dd,J＝8.3,2.6Hz,1H),6.60(d,J＝7.6Hz,1H),6.51(t,J＝2.1Hz,1H),5.18(s,2H),3.63(s,3H).13C NMR(101MHz,DMSO-d6)δ(ppm)＝159.7,139.3,138.4,136.4,130.1,127.0,126.8,124.8,122.1,120.1,119.5,119.3,113.6,115.7,112.7,112.4,101.8,55.3,49.1.HR-MS(ESI):m/z calcd forC19H16BrN3O([M+H]+)382.0550,Found 382.0544.
实施例51
3-(4-溴-1-(2-甲氧基苄基)-1-氢-咪唑-5-基)-1氢-吲哚(化合物A-30)
在实施例15的基础上，将正丙胺替换为2-甲氧基苄胺，制得化合物A-30。
鲜黄色固体，产率：70％。m.p.186.2–186.9℃.1H NMR(400MHz,DMSO-d6)δ(ppm)＝11.51(s,1H),7.81(s,1H),7.46(d,J＝8.1Hz,1H),7.38(d,J＝2.6Hz,1H),7.32(d,J＝7.9Hz,1H),7.18(dt,J＝19.7,7.7Hz,2H),7.05(t,J＝7.5Hz,1H),6.90(d,J＝8.2Hz,1H),6.79(t,J＝7.4Hz,1H),6.57(d,J＝7.5Hz,1H),5.07(s,2H),3.64(s,3H).13C NMR(101MHz,DMSO-d6)δ(ppm)＝156.5,138.4,136.4,129.5,127.9,127.0,126.9,125.3,125.0,122.1,120.8,120.1,119.5,115.5,112.4,111.1,101.8,55.7,44.7.HR-MS(ESI):m/z calcd forC19H16BrN3O([M+H]+)382.0550,Found 382.0563.
实施例52
3-(4-溴-1-(3-氟基苄基)-1-氢-咪唑-5-基)-1氢-吲哚(化合物A-31)
在实施例15的基础上，将正丙胺替换为3-氟基苄胺，制得化合物A-31。
白色固体，产率：65％。m.p.197.3–198.3℃.1H NMR(400MHz,DMSO-d6)δ(ppm)＝11.54(s,1H),7.97(d,J＝1.2Hz,1H),7.46(d,J＝8.1Hz,1H),7.37(t,J＝2.0Hz,1H),7.29–7.21(m,2H),7.15(t,J＝7.5Hz,1H),7.07–6.97(m,2H),6.70(t,J＝9.1Hz,2H),5.17(s,2H).13C NMR(101MHz,DMSO-d6)δ(ppm)＝163.7,161.3,140.5(d,J＝7.4Hz),138.5,136.3,131.0(d,J＝8.4Hz),126.9(d,J＝30.1Hz),124.8,123.1(d,J＝2.7Hz),122.1,120.1,119.4,115.9,114.8(d,J＝20.9Hz),114.0(d,J＝22.1Hz),112.4,101.6,48.7.19F NMR(376MHz,DMSO-d6)δ(ppm)＝-113.0.HR-MS(ESI):m/z calcd for C18H13BrFN3([M+H]+)370.0350,Found 370.0346.
实施例53
3-(4-溴-1-(2-氟基苄基)-1-氢-咪唑-5-基)-1氢-吲哚(化合物A-32)
在实施例15的基础上，将正丙胺替换为2-氟基苄胺，制得化合物A-32。
白色固体，产率：73％。m.p.210.7–211.3℃.1H NMR(400MHz,Acetone-d6)δ(ppm)＝10.75(s,1H),7.80(s,1H),7.52(d,J＝8.1Hz,1H),7.43–7.36(m,2H),7.32–7.25(m,1H),7.20(t,J＝7.6Hz,1H),7.11–7.01(m,3H),6.86–6.79(m,1H),5.26(s,2H).13C NMR(101MHz,DMSO-d6)δ(ppm)＝161.0,158.6,138.5,136.4,130.3(d,J＝8.2Hz),129.3(d,J＝3.7Hz),127.0,126.8,125.0(d,J＝3.6Hz),124.9,124.4(d,J＝14.5Hz),122.1,120.1,119.4,115.9,115.7(d,J＝20.7Hz),112.4,101.5,43.5(d,J＝4.5Hz).19F NMR(376MHz,DMSO-d6)δ(ppm)＝-118.5.HR-MS(ESI):m/z calcd for C18H13BrFN3([M+H]+)370.0350,Found370.0352.
实施例54
3-(4-溴-1-(4-氯基苄基)-1-氢-咪唑-5-基)-1氢-吲哚(化合物A-33)
在实施例15的基础上，将正丙胺替换为4-氯基苄胺，制得化合物A-33。
白色固体，产率：53％。m.p.209.9–219.9℃.1H NMR(400MHz,DMSO-d6)δ(ppm)＝11.52(s,1H),7.95(s,1H),7.45(d,J＝8.0Hz,1H),7.34(d,J＝2.6Hz,1H),7.27(d,J＝7.9Hz,3H),7.15(t,J＝7.5Hz,1H),7.04(t,J＝7.4Hz,1H),6.89(d,J＝8.1Hz,2H),5.14(s,2H).13C NMR(101MHz,DMSO-d6)δ(ppm)＝138.4,136.7,136.3,132.5,129.0,128.9,127.1,126.8,124.8,122.1,120.1,119.4,115.9,112.5,101.6,48.6.HR-MS(ESI):m/z calcd forC18H13BrClN3([M+H]+)386.0054,Found 386.0041.
实施例55
3-(4-溴-1-(4-溴基苄基)-1-氢-咪唑-5-基)-1氢-吲哚(化合物A-34)
在实施例15的基础上，将正丙胺替换为4-溴基苄胺，制得化合物A-34。
黄色固体，产率：31％。m.p.231.4–232.5℃.1H NMR(400MHz,Acetone-d6)δ(ppm)＝10.68(s,1H),7.83(s,1H),7.51(d,J＝8.2Hz,1H),7.44–7.35(m,3H),7.34(d,J＝2.7Hz,1H),7.22–7.17(m,1H),7.12–7.07(m,1H),6.92(d,J＝8.4Hz,2H),5.20(s,2H).13C NMR(101MHz,DMSO-d6)δ(ppm)＝138.4,137.1,136.3,131.8,129.3,127.1,126.8,124.8,122.1,121.1,120.1,119.4,115.9,112.5,101.6,48.6.HR-MS(ESI):m/z calcd forC18H13Br2N3([M+H]+)429.9549,Found 429.9557.
实施例56
3-(4-溴-1-(4-三氟甲基苄基)-1-氢-咪唑-5-基)-1氢-吲哚(化合物A-35)
在实施例15的基础上，将正丙胺替换为4-三氟甲基苄胺，制得化合物A-35。
鲜黄色固体，产率：21％。m.p.229.3–230.1℃.1H NMR(400MHz,Acetone-d6)δ(ppm)＝10.67(s,1H),7.89(s,1H),7.58(d,J＝8.1Hz,2H),7.50(d,J＝8.2Hz,1H),7.38–7.33(m,2H),7.21–7.15(m,3H),7.10–7.05(m,J＝8.0,7.0,1.1Hz,1H),5.34(s,2H).13C NMR(101MHz,DMSO-d6)δ(ppm)＝142.5,138.6,136.3,128.4(q,J＝32.0Hz),127.7,127.1,126.8,125.8(q,J＝3.6Hz),124.8,123.2,122.1,120.1,119.3,116.1,112.4,101.5,48.8.19F NMR(376MHz,Acetone-d6)δ(ppm)＝-63.1(s,3F).HR-MS(ESI):m/z calcd forC19H13BrF3N3([M+H]+)420.0318,Found 420.0309.
实施例57
3-(4-溴-1-(吡啶-3-基甲基)-1-氢-咪唑-5-基)-1氢-吲哚(化合物A-36)
在实施例15的基础上，将正丙胺替换为吡啶-3-基甲胺，制得化合物A-36。
黄色固体，产率：67％。m.p.180.6–181.7℃.1H NMR(400MHz,Acetone-d6)δ(ppm)＝10.72(s,1H),8.40(dd,J＝4.7,1.7Hz,1H),8.19(d,J＝1.8Hz,1H),7.88(s,1H),7.52(d,J＝8.2Hz,1H),7.38(dd,J＝7.7,1.7Hz,2H),7.35–7.31(m,1H),7.24–7.18(m,2H),7.12–7.07(m,1H),5.29(s,2H).13C NMR(101MHz,DMSO-d6)δ(ppm)＝149.2,148.6,138.4,136.3,135.1,133.1,127.1,126.7,124.7,124.0,122.2,120.2,119.3,116.0,112.5,101.6,47.0.HR-MS(ESI):m/z calcd for C17H13BrN4([M+H]+)353.0396,Found 353.0405.
实施例58
对合成的化合物3a-化合物5g、化合物A-1—化合物A-36进行杀菌活性测定：采用生长速率法，对6种农作物病菌：番茄早疫病菌(Alternaria solani)、草莓灰霉病菌(Botrytis cinrea)、苹果斑点病菌(Alternaria leaf spot)、水稻纹枯病菌(Rhizoctoniasolani)、小麦赤霉病菌(Gibberella zeae)、黄瓜炭疽病菌(Colletotrichum lagenarium)进行杀菌活性的测定。
实验仪器：双人双面净化工作台(苏州净化设备有限公司)、塑料培养皿(合肥新恩源生物技术有限公司)、电热恒温生化培养箱(上海精宏实验设备有限公司)、高压灭菌锅(TOMY SX-700)、5mm打孔器、接菌环、直尺等。
所需材料：马铃薯葡萄糖琼脂培养基(以下简称PDA)；硫酸链霉素(0.01g/mL)；活化的待测菌：将待测菌转接与PDA上，在25±1℃条件下培养2-15d，用于测定。
测定方法：化合物的抑菌活性分两批次进行，第一批为化合物3a-化合物5g，以Streptochlorin、多菌灵、啶酰菌胺为阳性对照药；第二批为化合物A-1—化合物A-36，以啶酰菌胺、蛇床子素、匹普利宁为阳性对照药。称取化合物，以N,N-二甲基甲酰胺(以下简称DMF)为溶剂配制成浓度25mg/mL的储备液，并以无供试品的DMF作为空白对照。加入至已灭菌的PDA培养基(50mL)中使化合物终浓度为50ppm，每组药品做三个重复，加入硫酸链霉素3-4滴，置于超净台中进行紫外灭菌处理。将已活化的待测菌打孔后，转接于培养基中，然后置于25℃培养箱培养。培养期间观察真菌的生长情况，测定真菌在不同供试品存在下的菌饼的直径，计算其抑菌生长率。测定结果如表1、表2所示。
Figure BDA0002731380150000211
表1.化合物3a-化合物5g的杀菌活性(供试品浓度：50ppm)
Figure BDA0002731380150000212
Figure BDA0002731380150000221
表2.化合物A-1-化合物A-36的抑菌活性(供试品浓度：50ppm)
Figure BDA0002731380150000222
Figure BDA0002731380150000231
根据杀菌活性结果可以得出以下结论：
(1)、所有化3-(5-咪唑基)吲哚类化合物都对多种常见农作物病菌表现出抑制活性，具有广谱的杀菌活性，部分杀菌活性优于商品化对照蛇床子素；对测试的6种菌种活性敏感程度有所差异，对水稻纹枯病菌(Rhizoctonia solani)、草莓灰霉病菌(Botrytiscinerea)、黄瓜炭疽病菌(Colletotrichum lagenarium)活性较好；
(2)、取代基中卤原子存在提升了化合物的活性，特别是氟原子的存在；
(3)、比较化合物A-7及其咪唑4位氯代衍生物A-19、4位溴代衍生物A-31之间的活性可以发现，在咪唑4位引入卤素有利于活性提高，而且一般而言，溴代衍生物活性略好于氯代衍生物。

Claims (8)

1.如式Ⅰ所示的3-(5-咪唑基)吲哚类化合物：
Figure FDA0002731380140000011
其中，其中，R选自C1～C4直链或支链烷基、C3～C6环烷基、取代或未取代的苯基取代的C1～C2烷基、C1～C2烷氧基取代的C1～C2烷基、5元～6元含氮杂环取代的C1～C2烷基；所述的取代苯基的取代基为邻、间、对位取代的或者多取代的C1～C2烷基、C1～C2烷氧基、卤素取代的C1～C2烷基、F、Cl、Br；
X选自H、Cl、Br。
2.根据权利要求1所述的3-(5-咪唑基)吲哚类化合物，其特征在于R选自C3～C4直链或支链烷基、环己烷基、苄基、取代苯基取代的甲基；所述的取代苯基的取代基为邻、间、对位取代的甲基、甲氧基、三氟甲基、F、Cl、Br。
3.根据权利要求1所述的3-(5-咪唑基)吲哚类化合物，其特征在于X选自H，R选自正丁基、环己烷基、苄基、取代苯基取代的甲基；所述的取代苯基的取代基为对位取代的甲基、甲氧基、三氟甲基、F、Cl、Br或邻位取代的F；
X选自Cl，R选自正丁基、1-异丁基、环己烷基、苄基、取代苯基取代的甲基；所述的取代苯基的取代基为对位取代的甲基、甲氧基、F、Cl、Br或邻位取代的F；
X选自Br，R选自C3～C4直链烷基、环己烷基、苄基、取代苯基取代的甲基；所述的取代苯基的取代基为对位取代的甲基、甲氧基、F、Cl、Br或或间位取代的F或邻位取代的甲基、甲氧基、F。
4.一种权利要求1所述的3-(5-咪唑基)吲哚类化合物的的制备方法，其特征在于X选自H时，合成路线如下：
Figure FDA0002731380140000012
X选自Cl、Br时，合成路线如下：
Figure FDA0002731380140000021
5.根据权利要求4所述的3-(5-咪唑基)吲哚类化合物的的制备方法，其特征在于X选自H时，以无水甲醇和无水乙二醇二甲醚为溶剂，常温下，吲哚-3-甲醛与伯胺RNH2反应生成亚胺，再在温度40～60℃下，在K2CO3的作用下，TosMIC与亚胺反应生成式Ⅰa所示的3-(5-咪唑基)吲哚类化合物；其中，所述的吲哚-3-甲醛与伯胺的摩尔比为1:1～2；所述的吲哚-3-甲醛与TosMIC的摩尔比为1:1～2；所述的吲哚-3-甲醛与K2CO3的摩尔比为1:1～2。
X选自Cl、Br时，以四氢呋喃和四氯化碳体积比为1:1的混合溶剂为溶剂，在温度40～60℃下，化合物Ⅰa与NCS或NBS反应生成式Ⅰb所示的3-(5-咪唑基)吲哚类化合物；其中，化合物Ⅰa与NCS或NBS的摩尔比为1:1～2。
6.权利要求1-3任一项所述的3-(5-咪唑基)吲哚类化合物在杀灭农作物致病菌中的应用。
7.根据权利要求6所述的应用，其特征在于所述的农作物致病菌为番茄早疫病菌、草莓灰霉病菌、苹果斑点病菌、水稻纹枯病菌、小麦赤霉病菌、黄瓜炭疽病菌。
8.根据权利要求7所述的应用，其特征在于所述的农作物致病菌为水稻纹枯病菌、草莓灰霉病菌、黄瓜炭疽病菌。
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