CN115073478A - 吲哚3,4位并氮杂卓环化合物、其制备方法及应用 - Google Patents
吲哚3,4位并氮杂卓环化合物、其制备方法及应用 Download PDFInfo
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- C07—ORGANIC CHEMISTRY
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- C07D487/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains three hetero rings
- C07D487/16—Peri-condensed systems
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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Abstract
本发明公开了吲哚3,4位并氮杂卓环化合物、其制备方法及应用，属于有机合成技术领域。本发明建立了一种独特的通过4‑胺基靛红类化合物与氨基丙二酸二乙酯缩合成亚胺引发的1,6‑氢迁移的合成方法，从以上原料出发，在高温条件下快速获得吲哚3,4位并氮杂卓环化合物，该方法简单实用，原子步骤经济性高，且合成的吲哚3,4位并氮杂卓环化合物为新骨架化合物，填补了吲哚3,4位并氮杂卓环化合物的空白。同时，本发明合成的吲哚3,4位并氮杂卓环化合物具备一定的杀螨活性，可用于制备杀螨药物，也可作为先导化合物，经改造后用于杀螨，存在较好的应用价值。
Description
技术领域
本发明属于有机合成技术领域，具体涉及吲哚3,4位并氮杂卓环化合物、其制备方法及应用。
背景技术
吲哚存在于各类天然产物和药物分子中，因为其独特的化学结构而展现出来的生理和药理活性受到世人的广泛关注。在诸多吲哚类活性分子中，3,4-吲哚并氮杂中环骨架是较为常见且重要的核心骨架。因其具有潜在的生物活性，在药物化学领域应用较为广泛。例如，Indolactam V可以作为蛋白激酶C激活剂，被广泛应用于抗菌、抗疟、抗癌及干细胞分化活性研究中(Chem.Rec.2019,19,320；Angew.Chem.Int.Ed.2013,52,4902)。Clavinealkaloid clavicipitic acid则具有抗肿瘤活性(Tetrahedron Lett.2020,61,151696)。它们均含有3,4-吲哚并氮杂中环骨架。
因此，开发和发展合成该结构骨架的方法对新药研发具有重要的推动意义，所合成的新骨架分子也将为药物活性筛选提供选择空间。
发明内容
本发明提供了一种基于吲哚骨架的3,4-位并氮杂卓环化合物的制备方法，该方法简单实用，原子步骤经济性高。
本发明的技术方案如下：
一种吲哚3,4位并氮杂卓环化合物，结构如式Ⅰ所示：
式Ⅰ中：
R1选自氢、苄基、甲基、乙基、烯丙基、环丙基、环丙甲基中的一种；
R2与R3成环，环选自全氢异吲哚、四氢吡咯或哌啶；
R4选自氢、甲基中的一种；
上述吲哚3,4位并氮杂卓环化合物的制备方法如下：
将4-胺基靛红类化合物和氨基丙二酸二乙酯溶于溶剂中，加入催化剂，于高温环境下反应，待反应完成，获得吲哚3,4位并氮杂卓环化合物。
在上述方案的基础上，4-胺基靛红类化合物的结构如式Ⅱ所示：
式Ⅱ中，
R1选自氢、苄基、甲基、乙基、烯丙基、环丙基、环丙甲基中的一种；
R2与R3成环，环选自全氢异吲哚、四氢吡咯或哌啶；
R4选自氢、甲基中的一种。
在上述方案的基础上，式Ⅱ所述4-胺基靛红类化合物可选自如下具体结构：
在上述方案的基础上，4-胺基靛红类化合物与氨基丙二酸二乙酯的摩尔比为1:1.5。
在上述方案的基础上，催化剂选自对甲苯磺酸、甲烷磺酸、三氟醋酸、三氟化硼乙醚、三氯化铁中的一种。
在上述方案的基础上，溶剂选自1,2-二氯乙烷、1,4-二氧六环、异丙醇、乙腈、N,N-二甲基甲酰胺中、甲苯、四氢呋喃的一种。
在上述方案的基础上，催化剂的用量为20mol％。
在上述方案的基础上，溶剂的用量为每摩尔4-胺基靛红类化合物添加10L溶剂。
在上述方案的基础上，所在高温环境为：温度100℃，空气气氛。
上述吲哚3,4位并氮杂卓环化合物具有螨虫抑制活性，基于此，本发明提供了上述吲哚3,4位并氮杂卓环化合物在制备具有杀螨作用的药物中的应用。
本发明的有益效果为：
本发明建立了一种独特的通过4-胺基靛红类化合物与氨基丙二酸二乙酯缩合成亚胺引发的1,6-氢迁移的合成方法，从以上原料出发，在高温条件下快速获得吲哚3,4位并氮杂卓环化合物，该方法简单实用，原子步骤经济性高，且合成的吲哚3,4位并氮杂卓环化合物为新骨架化合物，填补了吲哚3,4位并氮杂卓环化合物的空白。同时，反应组分结构多样性也证明了该方法具有广泛的合成应用前景。
具体实施方式
在本发明中，Me指代甲基，Et指代乙基，Bn指代苄基，iPr指代异丙基，Ph指代苯基，上述简写符号均为本领域常规用语，不存在歧义。发明中所使用的其它术语，除非有另外说明，一般具有本领域普通技术人员通常理解的含义。下面结合具体实施例，并参照数据进一步详细的描述本发明。以下实施例只是为了举例说明本发明，而非以任何方式限制本发明的范围。
(一)吲哚3,4位并氮杂卓环化合物合成条件的筛选
以4-胺基靛红和氨基丙二酸二乙酯为反应原料，筛选吲哚3,4位并氮杂卓环化合物的合成反应条件，具体如下：
取0.2mmol的4-胺基靛红和0.3mmol氨基丙二酸二乙酯于反应瓶中，加入2mL溶剂，20mol％催化剂，持续搅拌，在100℃下反应，通过薄层色谱板点样跟踪反应至原料反应完全，待反应完成后，使用硅胶柱进行分离纯化，将纯化后的产品旋蒸得目标产物。
化学反应式如下所示：
根据上述反应，设置平行试验组，使用不同的催化剂和溶剂。
催化剂分别为对甲苯磺酸(TsOH.H2O)、甲烷磺酸(MsOH)、三氟醋酸(TFA)、樟脑磺酸((-)-CSA)、三氟甲磺酸(TfOH)、三氟甲烷磺酸钪(Sc(OTf)3)、三氟甲烷磺酸铜(Cu(OTf)3)、三氟甲烷磺酸锌(Zn(OTf)3)、三氟化硼乙醚(BF3.OEt2)、三氯化铁(FeCl3)。
溶剂分别为1,2-二氯乙烷(DCE)、二氯甲烷(DCM)、N,N-二甲基甲酰胺(DMF)、四氢呋喃(THF)、1,4-二氧六环(1,4-dioxane)、乙腈(CH3CN)、乙醇(EtOH)。
试验组具体使用的催化剂、溶剂种类和浓度如表1所示：
表1
| Entry | Catalyst | Solvent | Yield(％) |
| 1 | - | DCE | 11 |
| 2 | TsOH·H<sub>2</sub>O | DCE | 12 |
| 3 | MsOH | DCE | 11 |
| 4 | TFA | DCE | 16 |
| 5 | (-)-CSA | DCE | trace |
| 6 | TfOH | DCE | trace |
| 7 | Sc(OTf)<sub>3</sub> | DCE | trace |
| 8 | Cu(OTf)<sub>2</sub> | DCE | trace |
| 9 | Zn(OTf)<sub>2</sub> | DCE | trace |
| 10 | BF<sub>3</sub>·OEt<sub>2</sub> | DCE | 11 |
| 11 | FeCl<sub>3</sub> | DCE | 44 |
| 12 | FeCl<sub>3</sub> | DCM | 22 |
| 13 | FeCl<sub>3</sub> | DMF | 22 |
| 14 | FeCl<sub>3</sub> | toluene | 22 |
| 15 | FeCl<sub>3</sub> | THF | 55 |
| 16 | FeCl<sub>3</sub> | 1,4-Dioxane | 49 |
| 17 | FeCl<sub>3</sub> | MeCN | 27 |
| 18 | FeCl<sub>3</sub> | EtOH | trace |
根据上述试验结果筛选出最佳的实验方案，即反应体系中，反应原料为0.2mmol4-胺基靛红类化合物和0.3mmol氨基丙二酸二乙酯，在0.04mmol FeCl3催化下，以2mL四氢呋喃作溶剂，在100℃下持续搅拌反应至原料反应完全。实施例1-10所述产物均以该最佳的反应条件为基础，通过替换不同的反应底物所得。
(二)吲哚3,4位并氮杂卓环化合物杀螨活性测试
测试吲哚3,4位并氮杂卓环化合物的杀螨活性，步骤如下：
1、样品的配制过程
精确称取10mg供试化合物样品，用DMF溶解并定容至2mL。如遇化合物不溶或溶解不完全，则加入适量DMSO进行溶解，配成5000ppm母液。取0.4mL母液再用0.1％吐温水溶液稀释定容至10mL，配成200ppm溶液。以10mg乙唑螨腈用DMF溶解作为阳性对照，取5mL备用。以“0.1％吐温水溶液4.8mL+DMF 0.2mL”为阴性对照。
2、喷雾接种过程
选取正常生长的两片真叶展开的豆苗植株，单株移至小盆中；植株恢复一夜后去掉一片真叶和中间生长点，保留一片真叶；将带有螨的叶片剪成小块，放置于处理过的豆苗叶片上，让螨自行转移至单株叶片上，每株接螨50-100头，2～3h后对其进行喷雾，喷雾时将待测液用喉头喷雾器均匀喷至叶片正反两面；喷雾后将实验材料置于阴凉通风处晾干后放在观察室，于温度25℃、相对湿度55％的条件下培养，48h后统计成螨的死亡情况，用毛笔轻触螨体，以其螯肢不动者为死亡。
计算方法：
螨虫致死率(％)＝(药前螨数－药后螨数)/药前螨数×100％
实验结果如表2所示。
表2
由表2可知，本发明合成的一系列吲哚并氮杂卓化合物具备一定的杀螨活性，可用于制备杀螨药物，也可作为先导化合物，经改造后用于杀螨，存在较好的应用价值。
实施例1-10的反应产物，其结构以及核磁共振数据如下所示：
实施例1
Yellow oil；24.1mg,52％yield；column chromatography eluent,petroleumether/EtOAc＝2:1；1H NMR(500MHz,Chloroform-d)δ7.29–7.20(m,4H),7.19–7.15(m,1H),7.06(dd,J＝8.7,7.5Hz,1H),6.26(d,J＝8.7Hz,1H),6.02(d,J＝7.4Hz,1H),4.99(d,J＝15.8Hz,1H),4.79(d,J＝15.7Hz,1H),4.36–4.28(m,1H),4.28–4.23(m,1H),4.10–4.01(m,1H),3.96(m,1H),3.57(m,1H),3.49(m,1H),3.28(dd,J＝8.5,6.4Hz,1H),2.54(m,1H),2.38(m,1H),2.23–2.06(m,1H),1.88(m,1H),1.27(t,J＝7.1Hz,3H),0.98(t,J＝7.1Hz,3H)；13CNMR(126MHz,CDCl3)δ167.9,165.6,164.2,158.6,146.3,145.2,135.9,134.8,128.7(2C),127.6,127.4(2C),108.9,102.1,98.4,81.6,66.7,62.2,61.76,49.3,43.9,30.8,23.8,14.1,13.8.HRMS(ESI-TOF)m/z:[M+H]+ calcd for C26H29N3O5 463.2107；found 4632103.
实施例2
Yellow oil；30.2mg,78％yield；column chromatography eluent,petroleumether/EtOAc＝2:1；1H NMR(500MHz,Chloroform-d)δ7.17(dd,J＝8.7,7.4Hz,1H),6.31(d,J＝8.8Hz,1H),6.13(d,J＝7.4Hz,1H),4.26(m,2H),4.01(m,2H),3.60(ddd,J＝9.9,8.1,5.7Hz,1H),3.51(dt,J＝9.7,7.0Hz,1H),3.28–3.23(m,1H),3.19(s,3H),2.53(m,1H),2.37(m,1H),2.18–2.08(m,1H),1.94–1.85(m,1H),1.26(t,J＝7.2Hz,3H),1.00(t,J＝7.1Hz,3H)；13C NMR(126MHz,CDCl3)δ167.9,165.7,164.2,158.7,147.3,145.1,134.8,109.0,101.8,97.3,81.5,66.7,62.2,61.7,49.3,30.8,26.4,23.8,14.0,13.9.HRMS(ESI-TOF)m/z:[M+H]+calcd for C20H25N3O5 387.1794；found 387.1780.
实施例3
Yellow oil；27.3mg,68％yield；column chromatography eluent,petroleumether/EtOAc＝2:1；1H NMR(500MHz,Chloroform-d)δ7.17(dd,J＝8.7,7.4Hz,1H),6.29(d,J＝8.7Hz,1H),6.15(d,J＝7.4Hz,1H),4.33–4.20(m,2H),4.08–4.01(m,1H),4.00–3.92(m,1H),3.82(m,1H),3.67(m,1H),3.59(m,1H),3.50(dt,J＝9.7,7.0Hz,1H),3.26(dd,J＝8.5,6.4Hz,1H),2.54(m,1H),2.43–2.32(m,1H),2.13(m,1H),1.89(m,1H),1.26(t,J＝7.1Hz,3H),1.22(t,J＝7.2Hz,3H),1.00(t,J＝7.1Hz,3H)；13C NMR(126MHz,CDCl3)δ167.9,165.7,163.7,158.8,146.4,145.3,134.8,108.7,102.0,97.4,81.5,66.6,62.1,61.7,49.3,34.9,30.8,23.8,14.0,13.8,13.1.HRMS(ESI-TOF)m/z:[M+H]+calcd for C21H27N3O5 401.1951；found 401.1957.
实施例4
Yellow oil；23.1mg,56％yield；column chromatography eluent,petroleumether/EtOAc＝2:1；1H NMR(500MHz,Chloroform-d)δ7.14(dd,J＝8.7,7.5Hz,1H),6.30(d,J＝8.7Hz,1H),6.13(d,J＝7.5Hz,1H),5.79(m,1H),5.22–5.10(m,2H),4.44–4.36(m,1H),4.32–4.22(m,3H),4.08–3.92(m,2H),3.59(m,1H),3.51(m,1H),3.27(dd,J＝8.5,6.4Hz,1H),2.55(dtd,J＝13.9,7.9,6.4Hz,1H),2.44–2.33(m,1H),2.19–2.07(m,1H),1.89(m,1H),1.27(t,J＝7.2Hz,3H),0.99(t,J＝7.1Hz,3H)；13C NMR(126MHz,CDCl3)δ167.9,165.7,164.2,158.7,147.3,145.1,134.8,109.0,101.8,97.3,81.5,66.7,62.2,61.7,49.3,30.8,26.4,23.8,14.1,14.0,13.9.HRMS(ESI-TOF)m/z:[M+H]+calcd for C22H27N3O5 413.1951；found 413.1959.
实施例5
Yellow oil；16.5mg,40％yield；column chromatography eluent,petroleumether/EtOAc＝2:1；1H NMR(500MHz,Chloroform-d)δ7.19–7.15(m,1H),6.41(d,J＝7.4Hz,1H),6.29(d,J＝8.7Hz,1H),4.25(m,3H),4.08–4.01(m,1H),3.96(m,1H),3.57(m,1H),3.49(m,1H),3.24(dd,J＝8.6,6.3Hz,1H),2.65–2.58(m,1H),2.57–2.49(m,1H),2.43–2.32(m,1H),2.11(m,1H),1.88(m,1H),1.25(d,J＝7.2Hz,3H),0.99(d,J＝7.2Hz,3H),0.97–0.77(m,4H)；13C NMR(126MHz,CDCl3)δ167.9,165.7,164.4,158.7,147.6,145.1,134.8,108.6,101.9,98.7,81.6,66.6,62.1,61.7,49.3,30.8,23.8,22.2,14.0,13.9,6.5,6.1.HRMS(ESI-TOF)m/z:[M+H]+calcd for C22H27N3O5 413.1951；found 413.1950.
实施例6
Yellow oil；18.8mg,44％yield；column chromatography eluent,petroleumether/EtOAc＝2:1；1H NMR(500MHz,Chloroform-d)δ7.17(dd,J＝8.7,7.5Hz,1H),6.29(d,J＝8.7Hz,1H),6.20(d,J＝7.4Hz,1H),4.27(m,2H),4.10–4.01(m,1H),4.00–3.92(m,1H),3.65–3.46(m,4H),3.28(dd,J＝8.5,6.3Hz,1H),2.55(m,1H),2.45–2.32(m,1H),2.12(m,1H),1.89(m,1H),1.27(t,J＝7.2Hz,3H),0.99(t,J＝7.1Hz,3H),0.44(m,2H),0.35(m,2H)；13C NMR(126MHz,CDCl3)δ167.9,165.7,163.7,158.8,146.4,145.3,134.8,108.7,102.0,97.4,81.5,66.7,62.1,61.7,49.3,34.9,30.8,23.8,14.0,13.8,13.1.HRMS(ESI-TOF)m/z:[M+H]+calcd for C23H29N3O5 427.2701；found 427.2698.
实施例7
Yellow oil；20.0mg,42％yield；column chromatography eluent,petroleumether/EtOAc＝2:1；1H NMR(500MHz,Chloroform-d)δ7.28–7.20(m,5H),7.17(t,J＝6.9Hz,1H),6.84(d,J＝7.6Hz,1H),5.95(d,J＝7.6Hz,1H),4.99(d,J＝15.7Hz,1H),4.75(d,J＝15.7Hz,1H),4.28(m,3H),4.12–3.98(m,4H),3.77–3.59(m,2H),3.28(t,J＝7.3Hz,1H),2.49–2.39(m,1H),2.36(m,1H),2.32(s,3H),2.04(m,1H),1.86–1.75(m,1H),1.28(t,J＝7.1Hz,3H),1.03(t,J＝7.1Hz,3H).；13C NMR(126MHz,CDCl3)δ167.9,165.4,163.9,158.8,147.1,144.6,137.9,135.9,128.7(2C),127.6,127.4(2C),118.5,103.8,98.9,81.1,69.5,62.2,61.7,52.7,43.8,30.1,25.1,23.4,14.1,13.9.HRMS(ESI-TOF)m/z:[M+H]+calcd forC27H31N3O5 477.2264；found 477.2260.
实施例8
Yellow oil；18.6mg,39％yield；column chromatography eluent,petroleumether/EtOAc＝2:1；1H NMR(500MHz,Chloroform-d)δ7.31–7.26(m,2H),7.26–7.21(m,2H),7.19–7.15(m,1H),7.05(dd,J＝8.5,7.5Hz,1H),6.40(d,J＝8.9Hz,1H),6.04(d,J＝7.5Hz,1H),4.94(d,J＝15.6Hz,1H),4.81(d,J＝15.7Hz,1H),4.66(d,J＝11.6Hz,1H),4.40(m,1H),4.23–3.97(m,5H),3.19(m,1H),1.84(m 1H),1.69(d,J＝13.6Hz,1H),1.65–1.59(m,1H),1.57–1.40(m,2H),1.28(t,J＝7.2Hz,4H),1.04(d,J＝7.1Hz,3H).13C NMR(126MHz,CDCl3)δ168.8,164.3,163.5,160.6,147.0,146.7,135.7,135.1,128.7(2C),127.7,127.5(2C),111.7,105.9,99.2,80.8,66.0,62.7,62.6,53.4,43.9(2C),26.0,24.5,23.6,13.9,13.9(2C).HRMS(ESI-TOF)m/z:[M+H]+Calcd for C27H32N3O5 478.2336；found 478.2339.
实施例9
Yellow oil；25.9mg,25％yield；mp 237–239℃；column chromatographyeluent,petroleum ether/EtOAc＝2:1；1H NMR(500MHz,Chloroform-d)δ7.29–7.21(m,4H),7.17(d,J＝7.1Hz,1H),7.08(dd,J＝8.7,7.5Hz,1H),6.26(d,J＝8.6Hz,1H),6.06(d,J＝7.5Hz,1H),5.01(d,J＝15.7Hz,1H),4.78(d,J＝15.7Hz,1H),4.37–4.21(m,3H),4.13–4.01(m,1H),3.92(m,1H),3.40(d,J＝9.3Hz,2H),2.79(d,J＝2.1Hz,1H),2.74(td,J＝9.8,5.0Hz,1H),2.56(m,1H),1.77(m,1H),1.60(m,2H),1.57–1.51(m,1H),1.47(dd,J＝11.3,2.9Hz,1H),1.29(t,J＝7.2Hz,3H),1.25–1.13(m,5H),1.10–1.01(m,1H),0.97(t,J＝7.1Hz,3H)；13C NMR(126MHz,CDCl3)δ167.8,165.8,164.2,157.8,146.4,145.9,135.9,134.7,128.7(2C),127.6,127.4(2C),108.8,102.6,98.7,82.1,73.0,62.1,61.8,51.6,43.9,43.1,33.8,29.5,24.7,24.4,21.6,14.0,13.8.HRMS(ESI-TOF)m/z:[M+H]+calcd forC30H35N3O5 517.2577；found 517.2570.
实施例10
Yellow oil；25.9mg,25％yield；mp 220-224℃；column chromatographyeluent,petroleum ether/EtOAc＝2:1；1H NMR(500MHz,Chloroform-d)δ9.37(s,1H),7.12(t,J＝8.0Hz,1H),6.27(d,J＝8.7Hz,1H),6.19(d,J＝7.4Hz,1H),4.31–4.22(m,3H),4.09–3.95(m,3H),3.59(m,1H),3.50(m,1H),3.25(dd,J＝8.5,6.3Hz,1H),2.54(m,1H),2.38(m,1H),2.13(m,1H),1.90(m,1H),1.69–1.59(m,1H),1.42–1.32(m,1H),1.26(t,J＝7.1Hz,3H),0.99(t,J＝7.1Hz,3H)；13C NMR(126MHz,CDCl3)δ167.8,165.8,164.2,157.8,146.3,145.8,135.9,134.7,128.7,127.6,127.4,127.3,108.8,102.6,98.6,82.1,72.9,62.0,61.8,51.2,43.9,43.0,33.7,29.4,24.6,24.4,21.5,14.0,13.8.HRMS(ESI-TOF)m/z:[M+H]+calcd for C30H35N3O5 373.1638；found 373.1632.
以上所述，仅是本发明的较佳实施例而已，并非是对本发明作其它形式的限制，任何熟悉本专业的技术人员可能利用上述揭示的技术内容加以变更或改型为等同变化的等效实施例。但是凡是未脱离本发明技术方案内容，依据本发明的技术实质对以上实施例所作的任何简单修改、等同变化与改型，仍属于本发明技术方案的保护范围。
Claims (10)
1.一种吲哚3,4位并氮杂卓环化合物，其特征在于，结构如式Ⅰ所示：
式Ⅰ中，
R1选自氢、苄基、甲基、乙基、烯丙基、环丙基、环丙甲基中的一种；
R2与R3成环，环选自全氢异吲哚、四氢吡咯或哌啶；
R4选自氢、甲基中的一种。
2.权利要求1所述吲哚3,4位并氮杂卓环化合物的制备方法，其特征在于，步骤如下：
将4-胺基靛红类化合物和氨基丙二酸二乙酯溶于溶剂中，加入催化剂，于高温环境下反应，待反应完成，获得吲哚3,4位并氮杂卓环化合物。
3.根据权利要求2所述的制备方法，其特征在于，4-胺基靛红类化合物的结构如式Ⅱ所示：
式Ⅱ中，
R1选自氢、苄基、甲基、乙基、烯丙基、环丙基、环丙甲基中的一种；
R2与R3成环，环选自全氢异吲哚、四氢吡咯或哌啶；
R4选自氢、甲基中的一种。
4.根据权利要求2所述的制备方法，其特征在于，所述4-胺基靛红类化合物与氨基丙二酸二乙酯的摩尔比为1:1.5。
5.根据权利要求2所述的制备方法，其特征在于，所述催化剂选自对甲苯磺酸、甲烷磺酸、三氟醋酸、三氟化硼乙醚、三氯化铁中的一种。
6.根据权利要求2所述的制备方法，其特征在于，所述溶剂选自1,2-二氯乙烷、1,4-二氧六环、异丙醇、乙腈、N,N-二甲基甲酰胺中、甲苯、四氢呋喃的一种。
7.根据权利要求2所述的制备方法，其特征在于，所述催化剂的用量为20mol％。
8.根据权利要求2所述的制备方法，其特征在于，所述溶剂的用量为每摩尔4-胺基靛红类化合物添加10L溶剂。
9.根据权利要求2所述的制备方法，其特征在于，所在高温环境为：温度100℃，空气气氛。
10.权利要求1所述吲哚3,4位并氮杂卓环化合物在制备具有杀螨作用的药物中的应用。
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| CN108912127A (zh) * | 2018-08-27 | 2018-11-30 | 青岛农业大学 | 一种基于靛红骨架的苯并[b,e]氮杂卓化合物及其制备方法 |
| WO2021112478A1 (ko) * | 2019-12-05 | 2021-06-10 | 덕산네오룩스 주식회사 | 유기전기소자용 화합물, 이를 이용한 유기전기소자 및 그 전자 장치 |
| CN113121548A (zh) * | 2021-04-23 | 2021-07-16 | 青岛农业大学 | 一种吲哚并八元中环化合物及其制备方法 |
| CN113501825A (zh) * | 2021-07-13 | 2021-10-15 | 青岛农业大学 | 一种具有生物活性的3,4-位稠杂七元杂环的氧化吲哚烯结构及其合成方法和应用 |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN108912127A (zh) * | 2018-08-27 | 2018-11-30 | 青岛农业大学 | 一种基于靛红骨架的苯并[b,e]氮杂卓化合物及其制备方法 |
| WO2021112478A1 (ko) * | 2019-12-05 | 2021-06-10 | 덕산네오룩스 주식회사 | 유기전기소자용 화합물, 이를 이용한 유기전기소자 및 그 전자 장치 |
| CN113121548A (zh) * | 2021-04-23 | 2021-07-16 | 青岛农业大学 | 一种吲哚并八元中环化合物及其制备方法 |
| CN113501825A (zh) * | 2021-07-13 | 2021-10-15 | 青岛农业大学 | 一种具有生物活性的3,4-位稠杂七元杂环的氧化吲哚烯结构及其合成方法和应用 |
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