CN108610277A - 3-叔胺四取代氧化吲哚化合物及其制备方法 - Google Patents

3-叔胺四取代氧化吲哚化合物及其制备方法 Download PDF

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CN108610277A
CN108610277A CN201810230684.2A CN201810230684A CN108610277A CN 108610277 A CN108610277 A CN 108610277A CN 201810230684 A CN201810230684 A CN 201810230684A CN 108610277 A CN108610277 A CN 108610277A
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刘雄利
徐圣文
杨楷模
刘欢欢
岳静
陈爽
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Guizhou University
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Abstract

本发明公开了一种3‑叔胺四取代氧化吲哚化合物，本发明以各种取代的3‑卤氧化吲哚，以无机碱为催化剂，直接以二级环胺作溶剂和反应底物在加温条件下发生3‑叔胺基化反应，获得3‑叔胺四取代氧化吲哚化合物，该类氧化吲哚骨架可以为生物活性筛选提供化合物源，对药物的筛选和制药行业具有重要的应用价值。本发明操作简单易行，原料合成便宜易得，可以在无溶剂中进行，也具有较好的空气稳定性，适用性广，对于各种取代基都有很好的兼容性。

Description

3-叔胺四取代氧化吲哚化合物及其制备方法
技术领域
本发明涉及化学技术领域，尤其是一种3-叔胺四取代氧化吲哚化合物及其制备方法。
背景技术
3-叔胺基氧化吲哚广泛存在于合成药物和天然产物中，吸引了许多化学工作者及医药化学团队的广泛关注，例如，具有抗菌和抗肿瘤活性的天然产物分子psychotrimine，则是从植物psychotria rostrata中分离得到；血管加压素受体拮抗剂SSR-149415也含有3-叔胺基四取代氧化吲哚骨架结构。因此，采用方法学合成更多类型的3-叔胺基氧化吲哚，可以为吲哚类化合物的新药开发和成药性研究奠定物质基础，对药物的筛选和制药行业具有重要的应用价值。
发明内容
本发明的目的是：提供一种3-叔胺四取代氧化吲哚化合物及其制备方法，它是一类重要的医药中间体类似物和药物分子类似物，对药物筛选和制药行业具有重要的应用价值，且其合成方法非常经济简便。
本发明是这样实现的：3-叔胺四取代氧化吲哚化合物，该化合物具有如下通式(Ⅰ)的结构：
式(I)中，R为苄基或取代的苄基；Y为C或氧或硫；n为1或2。
将各种取代的3-卤氧化吲哚，以无机碱为催化剂，直接以二级环胺作溶剂和反应底物在加温条件下发生3-叔胺基化反应，获得3-叔胺四取代氧化吲哚化合物。
合成路线如下：
其中各种取代的3-卤氧化吲哚，二级环胺2的结构式，其取代基满足R为苄基、取代的苄基；Y为C或氧或硫；n为1或2；X为Cl或Br。
所述的无机碱为碳酸钠或碳酸钾或磷酸钠或磷酸钾。
所述的反应温度为50-100℃。
所推测的反应机理如下：
3-卤氧化吲哚1在无机碱催化下，脱去卤化氢生成中间体；中间体然后在二级环胺2亲核进攻下发生3-叔胺基化取代反应得到产物3-叔胺四取代氧化吲哚化合物3，副产物卤化氢被生成的三级胺产物中和成有机盐，促使反应进行完全。
通过采用上述技术方案，以各种取代的3-卤氧化吲哚，以无机碱为催化剂，直接以二级环胺作溶剂和反应底物在加温条件下发生3-叔胺基化反应，获得3-叔胺四取代氧化吲哚化合物，该类氧化吲哚骨架可以为生物活性筛选提供化合物源，对药物的筛选和制药行业具有重要的应用价值。本发明操作简单易行，原料合成便宜易得，可以在无溶剂中进行，也具有较好的空气稳定性，适用性广，对于各种取代基都有很好的兼容性。
附图说明
附图1及附图2为本发明的实施例的化合物3aa-1谱图数据；
附图3及附图4为本发明的实施例的化合物3aa谱图数据；
附图5及附图6为本发明的实施例的化合物3bf-1谱图数据；
附图7及附图8为本发明的实施例的化合物3bb谱图数据
具体实施方式
本发明的实施例1：3-苄基氯取代氧化吲哚(1a)128.5mg(0.5mmol)溶解于吗啉(2mL)中，加入10.6毫克Na2CO3(20mol％)，搅拌下于65℃反应5h(TLC检测)。冷却至室温,直接经硅胶柱层析[洗脱剂：V(乙酸乙酯)/V(石油醚)＝1/10]纯化得淡黄色油状液体3aa140.2mg,收率91％。核磁共振和高分辨质谱测试等结果如下：1H NMR(CDCl3,500MHz)δ:2.73-2.80(m,4H),3.20(d,J＝12.5Hz,1H),3.37(d,J＝12.5Hz,1H),3.69-3.71(m,4H),6.61(d,J＝7.5Hz,1H),6.81(d,J＝7.5Hz,2H),6.93-7.07(m,4H),7.13-7.16(m,1H),7.34(d,J＝7.5Hz,1H),8.55(br s,1H)；13C NMR(CDCl3,125MHz)δ:40.5,47.5,67.3,72.0,109.8,122.3,125.1,126.4,127.5,128.7,128.8,130.2,134.4,140.9,178.8；HR-MS(ESI-TOF)m/z:Calcd for C19H20N2NaO2{[M+Na]+}331.1417,found 331.125.
化合物3ab至3bh的制备方法同化合物3aa，投料比与化合物3aa相同，可得到化合物3ab至3bh，反应见表1和表2，但需强调的是本发明的化合物不限于表1所表示的内容。
表1为一种3-吗啉或硫代吗啉四取代氧化吲哚的化学结构
本实施例制备化合物3ab:淡黄色油状物；产率88％；1H NMRδ:2.12(s,3H),2.70-2.79(m,4H),3.16(d,J＝12.5Hz,1H),3.32(d,J＝12.5Hz,1H),3.67-3.69(m,4H),6.62(d,J＝7.5Hz,1H),6.69(d,J＝8.0Hz,2H),6.74(d,J＝8.0Hz,2H),7.02-7.05(m,1H),7.11-7.15(m,1H),7.32(d,J＝7.5Hz,1H),8.91(br s,1H)；13C NMRδ:20.8,39.9,47.4,67.2,72.1,109.8,122.1,125.0,128.2,128.7,128.8,130.0,131.2,135.8,141.1,179.1；HR-MS(ESI-TOF)m/z:Calcd for C20H22N2NaO2{[M+Na]+}345.1573,found 345.1573。
本实施例制备化合物3ac:淡黄色油状物；产率89％；1H NMRδ:2.73-2.80(m,4H),3.18(d,J＝12.5Hz,1H),3.33(d,J＝13.0Hz,1H),3.62(s,3H),3.72(s,4H),6.49(d,J＝8.0Hz,2H),6.67(d,J＝7.5Hz,1H),6.74(d,J＝8.5Hz,2H),7.06-7.09(m,1H),7.16-7.19(m,1H),7.36(d,J＝7.5Hz,1H),8.90(br s,1H)；13C NMRδ:39.5,47.5,54.8,67.2,72.1,109.9,112.8,122.1,125.0,126.2,128.7,128.8,131.1,141.1,157.9,179.1；HR-MS(ESI-TOF)m/z:Calcd for C20H22N2NaO3{[M+Na]+}361.1523,found 361.1529。
本实施例制备化合物3ad:淡黄色油状物；产率87％；1H NMRδ:2.71-2.79(m,4H),3.14(d,J＝12.5Hz,1H),3.32(d,J＝12.5Hz,1H),3.68-3.71(m,4H),6.64-6.69(m,3H),7.05-7.08(m,3H),7.15-7.18(m,1H),7.33(d,J＝7.0Hz,1H),8.73(br s,1H)；13C NMRδ:39.9,47.5,67.3,71.9,110.1,120.7,122.5,125.1,128.4,129.1,130.7,132.0,133.5,141.0,178.8；HR-MS(ESI-TOF)m/z:Calcd for C19H19BrN2NaO2{[M+Na]+}409.0522,found409.0521。
本实施例1制备化合物3ae:淡黄色油状物；产率91％；1H NMRδ:2.71-2.79(m,4H),3.17(d,J＝12.5Hz,1H),3.35(d,J＝12.5Hz,1H),3.69-3.71(m,4H),6.60-6.66(m,3H),6.74-6.77(m,2H),7.05-7.08(m,1H),7.15-7.18(m,1H),7.34(d,J＝7.0Hz,1H),8.86(brs,1H)；13C NMRδ:39.6,47.5,67.2,72.1,109.9,114.2(d,JCF＝21.3Hz),122.4,125.0,128.5,129.0,131.6,131.7,141.0,161.5(d,JCF＝243.8Hz),179.0；HR-MS(ESI-TOF)m/z:Calcd for C19H19FN2NaO2{[M+Na]+}349.1323,found 349.1320。
本实施例制备化合物3af:淡黄色油状物；产率91％；1H NMRδ:2.76-2.86(m,4H),3.23(d,J＝12.5Hz,1H),3.40(d,J＝12.5Hz,1H),3.73-3.75(m,4H),6.57(d,J＝10.0Hz,1H),6.65-6.69(m,2H),6.72-6.76(m,1H),6.94-6.98(m,1H),7.08-7.11(m,1H),7.17-7.20(m,1H),7.36(d,J＝6.0Hz,1H),8.84(br s,1H)；13C NMRδ:40.1,47.4,67.3,71.8,110.0,113.4(d,JCF＝21.3Hz),113.5,117.0(d,JCF＝21.3Hz),122.4,125.0,126.0,128.3,128.8,128.9,129.0,137.1,140.9,161.9(d,JCF＝223.8Hz),178.7；HR-MS(ESI-TOF)m/z:Calcdfor C19H19FN2NaO2{[M+Na]+}349.1323,found 349.1327。
本实施例制备化合物3bb:淡黄色油状物；产率93％；1H NMRδ:2.14(s,3H),2.67(s,4H),3.01(s,4H),3.17(d,J＝12.5Hz,1H),3.27(d,J＝12.5Hz,1H),6.62-6.67(m,3H),6.74(d,J＝8.0Hz,2H),7.04-7.07(m,1H),7.14-7.16(m,1H),7.31(d,J＝7.5Hz,1H),8.63(br s,1H)；13C NMRδ:20.9,28.5,40.5,49.8,72.9,109.9,122.3,124.9,128.2,128.7,129.1,130.1,131.1,135.9,140.8,179.3；HR-MS(ESI-TOF)m/z:Calcd for C20H22N2NaOS{[M+Na]+}361.1345,found 361.1352。
本实施例制备化合物3be:淡黄色油状物；产率95％；1H NMRδ:2.67-2.69(m,4H),2.98-3.05(m,4H),3.18(d,J＝12.5Hz,1H),3.29(d,J＝12.5Hz,1H),6.60-6.66(m,3H),6.71-6.74(m,2H),7.06-7.09(m,1H),7.16-7.19(m,1H),7.33(d,J＝7.5Hz,1H),8.66(brs,1H)；13C NMRδ:28.5,40.2,49.8,72.9,109.9,114.3(d,JCF＝21.3Hz),122.5,124.9,128.9(d,JCF＝20.0Hz),131.6,131.7,140.7,161.5(d,JCF＝243.8Hz),179.1；HR-MS(ESI-TOF)m/z:Calcd for C19H19FN2NaOS{[M+Na]+}365.1094,found 365.1099。
本实施例制备化合物3bg:淡黄色油状物；产率90％；1H NMRδ:1.16(s,9H),2.67(s,4H),3.01-3.03(m,4H),3.20-3.27(m,2H),6.62(d,J＝7.5Hz,1H),6.72(d,J＝8.0Hz,2H),6.99(d,J＝8.0Hz,2H),7.02-7.05(m,1H),7.12-7.15(m,1H),7.26-7.29(m,1H),8.64(br s,1H)；13C NMRδ:28.5,31.2,34.1,40.3,49.7,72.7,109.9,122.2,124.3,124.9,128.7,129.1,129.8,131.2,140.8,149.2,179.3；HR-MS(ESI-TOF)m/z:Calcd forC23H28N2NaOS{[M+Na]+}403.1815,found 403.1815。
本实施例制备化合物3bh:淡黄色油状物；产率91％；1H NMRδ:2.68-2.70(m,4H),3.02-3.04(m,4H),3.18(d,J＝12.5Hz,1H),3.27(d,J＝10.0Hz,1H),6.66(d,J＝7.5Hz,1H),6.74(d,J＝8.0Hz,1H),6.82-6.86(m,1H),6.91(s,1H),7.06-7.09(m,1H),7.15-7.20(m,2H),7.27-7.30(m,1H),8.53(br s,1H)；13C NMRδ:28.6,40.5,49.8,72.6,110.1,121.4,122.5,124.9,128.6,128.9,129.0,129.1,129.6,133.2,136.8,140.7,178.7；HR-MS(ESI-TOF)m/z:Calcd for C19H19BrN2NaOS{[M+Na]+}425.0294,found 425.0290。
化合物3aa-1至3bi-1的制备方法同化合物3aa，投料比与化合物3aa相同，可得到化合物3aa-1至3bi-1，反应见表1和表2，但需强调的是本发明的化合物不限于表2所表示的内容。
表2表1为一种3-哌啶或吡咯烷氧化吲哚的化学结构
本实施例制备化合物3aa-1:淡黄色油状物；产率90％；1H NMR(CDCl3,500MHz)δ:1.43(d,J＝5.0Hz,2H),1.55-1.60(m,4H),2.68-2.70(m,4H),3.25(d,J＝12.5Hz,1H),3.35(d,J＝12.5Hz,1H),6.60(d,J＝7.5Hz,1H),6.79-6.81(m,2H),6.91-6.94(m,2H),6.96-7.00(m,1H),7.01-7.04(m,1H),7.10-7.14(m,1H),7.35(d,J＝7.5Hz,1H),8.69(br s,1H)；13C NMR(CDCl3,125MHz)δ:24.6,26.4,41.1,48.2,72.7,109.6,121.9,125.0,126.2,127.4,128.4,129.5,130.2,134.9,140.9,179.6；HRMS(ESI-TOF)m/z:Calcd.forC20H22N2NaO[M+Na]+:329.1630；Found:329.1639。
本实施例制备化合物3ab-1:淡黄色油状物；产率93％；1H NMR(CDCl3,500MHz)δ:1.42(s,2H),1.55-1.58(m,4H),2.13(s,3H),2.68(s,4H),3.22(d,J＝12.5Hz,1H),3.31(d,J＝12.5Hz,1H),6.60(d,J＝7.5Hz,1H),6.68(d,J＝8.0Hz,2H),6.73(d,J＝7.5Hz,2H),7.01-7.04(m,1H),7.11-7.13(m,1H),7.33(d,J＝7.5Hz,1H),8.59(br s,1H)；13C NMR(CDCl3,125MHz)δ:20.9,24.7,26.4,40.6,48.1,72.7,109.6,121.9,125.0,128.1,128.3,129.6,130.1,131.7,135.6,141.0,179.6；HRMS(ESI-TOF)m/z:Calcd.for C21H24N2NaO[M+Na]+:343.1786；Found:343.1787。
本实施例制备化合物3ac-1:淡黄色油状物；产率87％；1H NMR(CDCl3,500MHz)δ:1.47(s,2H),1.60-1.62(m,4H),2.72(s,4H),3.24(d,J＝12.5Hz,1H),3.33(d,J＝12.5Hz,1H),3.66(s,3H),6.52(d,J＝8.5Hz,2H),6.65(d,J＝7.5Hz,1H),6.74(d,J＝8.5Hz,2H),7.06-7.09(m,1H),7.16-7.19(m,1H),7.38(d,J＝7.5Hz,1H),8.26(br s,1H)；13C NMR(CDCl3,125MHz)δ:24.7,26.5,40.2,48.2,54.9,72.8,109.6,112.8,122.0,125.1,126.8,128.4,129.7,131.2,140.9,157.9,179.5；HRMS(ESI-TOF)m/z:Calcd.for C21H24N2NaO2[M+Na]+:359.1735；Found:359.1731。
本实施例制备化合物3ad-1:淡黄色油状物；产率85％；1H NMR(CDCl3,500MHz)δ:1.45(d,J＝5.0Hz,2H),1.58-1.60(m,4H),2.09(s,3H),2.73(s,4H),3.34(s,2H),6.62(d,J＝8.0Hz,1H),6.84-6.98(m,5H),7.12-7.15(m,1H),7.20(d,J＝7.5Hz,1H),7.82(br s,1H)；13C NMR(CDCl3,125MHz)δ:20.2,24.7,26.5,36.4,48.1,72.2,109.4,122.0,125.0,125.4,126.4,128.4,130.0,130.3,133.7,137.4,140.7,179.5；HRMS(ESI-TOF)m/z:Calcd.for C21H24N2NaO[M+Na]+:343.1786；Found:343.1786。
本实施例制备化合物3ae-1:淡黄色油状物；产率92％；1H NMR(CDCl3,500MHz)δ:1.43(d,J＝5.5Hz,2H),1.56-1.59(m,4H),2.65-2.70(m,4H),2.22(d,J＝13.0Hz,1H),3.31(d,J＝12.5Hz,1H),6.59-6.65(m,3H),6.73-6.76(m,2H),7.03-7.06(m,1H),7.13-7.16(m,1H),7.35(d,J＝7.5Hz,1H),8.85(br s,1H)；13C NMR(CDCl3,125MHz)δ:24.6,26.4,40.2,48.2,72.8,109.8,114.2(d,JCF＝21.3Hz),122.1,125.0,128.6,129.3,131.6,140.9,161.5(d,JCF＝242.5Hz),179.6；HRMS(ESI-TOF)m/z:Calcd.for C20H21FN2NaO[M+Na]+:347.1536；Found:347.1542。
本实施例制备化合物3af-1:淡黄色油状物；产率90％；1H NMR(CDCl3,500MHz)δ:1.42-1.45(m,2H),1.56-1.61(m,4H),2.69(s,4H),3.19(d,J＝12.5Hz,1H),3.31(d,J＝12.0Hz,1H),6.61(d,J＝8.0Hz,1H),6.68(d,J＝8.5Hz,2H),7.03-7.09(m,3H),7.13-7.17(m,1H),7.33(d,J＝7.5Hz,1H),7.86(br s,1H)；13C NMR(CDCl3,125MHz)δ:24.6,26.5,40.5,48.2,72.4,109.7,120.5,122.2,125.0,128.7,129.3,130.6,132.0,134.0,140.6,178.8；HRMS(ESI-TOF)m/z:Calcd.for C20H21BrN2NaO[M+Na]+:407.0735；Found:407.0746。
本实施例制备化合物3ag-1:淡黄色油状物；产率93％；1H NMR(CDCl3,500MHz)δ:1.43(d,J＝5.0Hz,2H),1.55-1.60(m,4H),2.65-2.70(m,4H),3.21(d,J＝12.5Hz,1H),3.31(d,J＝12.5Hz,1H),6.64(d,J＝8.0Hz,1H),6.72(d,J＝8.5Hz,2H),6.89(d,J＝8.5Hz,2H),7.02-7.06(m,1H),7.13-7.16(m,1H),7.33(d,J＝7.0Hz,1H),8.76(br s,1H)；13C NMR(CDCl3,125MHz)δ:24.6,26.4,40.4,48.1,72.6,109.8,122.1,125.0,127.5,128.6,129.2,131.6,132.2,133.4,140.8,179.5；HRMS(ESI-TOF)m/z:Calcd.for C20H21ClN2NaO[M+Na]+:363.1240；Found:363.1240。
本实施例制备化合物3ah-1:淡黄色油状物；产率89％；1H NMR(CDCl3,500MHz)δ:1.44(s,2H),1.57-1.59(m,4H),2.69(d,J＝5.0Hz,4H),3.25(d,J＝12.5Hz,1H),3.33(d,J＝12.5Hz,1H),6.50(d,J＝10.0Hz,1H),6.61-6.65(m,2H),6.68-6.71(m,1H),6.87-6.92(m,1H),7.02-7.05(m,1H),7.12-7.16(m,1H),7.32(d,J＝7.0Hz,1H),8.80(br s,1H)；13CNMR(CDCl3,125MHz)δ:24.7,26.5,40.8,48.2,72.5,109.9,113.2,113.4,117.0(d,JCF＝21.3Hz),122.2,125.0,126.1,128.7,128.8,129.2,137.6,141.0,162.0(d,JCF＝243.8Hz),179.5；HRMS(ESI-TOF)m/z:Calcd.for C20H21FN2NaO[M+Na]+:347.1536；Found:347.1538。
本实施例制备化合物3ai-1:淡黄色油状物；产率87％；1H NMR(CDCl3,500MHz)δ:1.43-1.46(m,2H),1.58(d,J＝6.0Hz,4H),2.70(s,4H),3.22(d,J＝15.5Hz,1H),3.29(d,J＝15.5Hz,1H),6.65(d,J＝9.5Hz,1H),6.77-6.85(m,2H),6.93(s,1H),7.04-7.08(m,1H),7.13-7.18(m,2H),7.32(d,J＝9.0Hz,1H),8.51(br s,1H)；13C NMR(CDCl3,125MHz)δ:24.6,26.4,40.7,48.2,72.4,109.8,121.3,122.2,125.0,128.7,128.9,129.0,129.1,129.4,133.2,137.4,140.8,179.1；HRMS(ESI-TOF)m/z:Calcd.for C20H21BrN2NaO[M+Na]+:407.0735；Found:407.0741。
本实施例制备化合物3ba-1:淡黄色油状物；产率85％；1H NMR(CDCl3,500MHz)δ:1.22-1.27(m,4H),2.74-2.78(m,2H),2.92-2.95(m,2H),3.30(d,J＝12.5Hz,1H),3.50(d,J＝12.5Hz,1H),6.59(d,J＝7.5Hz,1H),6.74-6.81(m,1H),6.85(d,J＝7.0Hz,1H),6.96-7.04(m,4H),7.10-7.12(m,1H),7.39(d,J＝7.5Hz,1H),8.22(br s,1H)；13C NMR(CDCl3,125MHz)δ:23.2,42.5,47.0,70.2,109.5,122.1,125.0,126.3,127.4,127.5,128.5,129.8,130.2,130.4,134.9,140.6,179.4；HRMS(ESI-TOF)m/z:Calcd.for C19H20N2NaO[M+Na]+:315.1473；Found:315.1477。
本实施例制备化合物3bb-1:淡黄色油状物；产率90％；1H NMR(CDCl3,500MHz)δ:1.73(s,4H),2.13(s,3H),2.73-2.76(m,2H),2.89-2.91(m,2H),3.27(d,J＝12.5Hz,1H),3.44(d,J＝12.5Hz,1H),6.60(d,J＝7.5Hz,1H),6.71-6.76(m,4H),6.99-7.03(m,1H),7.09-7.13(m,1H),7.36(d,J＝7.0Hz,1H),8.83(br s,1H)；13C NMR(CDCl3,125MHz)δ:20.9,23.2,42.0,46.9,70.2,109.7,122.0,124.9,128.2,128.4,129.8,130.0,131.7,135.6,140.8,179.8；HRMS(ESI-TOF)m/z:Calcd.for C20H22N2NaO[M+Na]+:329.1630；Found:329.1630。
本实施例制备化合物3bc-1:淡黄色油状物；产率85％；1H NMR(CDCl3,500MHz)δ:1.78(s,4H),2.77-2.79(m,2H),2.92-2.94(m,2H),3.29(d,J＝12.5Hz,1H),3.46(d,J＝13.0Hz,1H),3.65(s,3H),6.52(d,J＝8.5Hz,2H),6.66(d,J＝7.5Hz,1H),6.78(d,J＝9.0Hz,2H),7.05-7.08(m,1H),7.15-7.18(m,1H),7.41(d,J＝7.0Hz,1H),8.59(br s,1H)；13C NMR(CDCl3,125MHz)δ:23.3,41.7,47.0,54.9,70.4,109.7,112.8,122.1,125.0,126.9,128.5,130.0,131.2,140.8,158.0,179.8；HRMS(ESI-TOF)m/z:Calcd.for C20H22N2NaO2[M+Na]+:345.1579；Found:345.1579。
本实施例制备化合物3be-1:淡黄色油状物；产率87％；1H NMR(CDCl3,500MHz)δ:1.74(s,4H),2.73-2.75(m,2H),2.89-2.91(m,2H),3.27(d,J＝13.0Hz,1H),3.45(d,J＝12.5Hz,1H),6.60-6.65(m,3H),6.77-6.80(m,2H),7.02-7.05(m,1H),7.12-7.16(m,1H),7.37(d,J＝7.0Hz,1H),8.90(br s,1H)；13C NMR(CDCl3,125MHz)δ:23.2,41.6,46.9,70.2,109.8,114.2(d,JCF＝21.3Hz),122.2,124.9,128.7,129.5,131.6,140.7,161.5(d,JCF＝243.8Hz),179.8；HRMS(ESI-TOF)m/z:Calcd.for C19H19FN2NaO[M+Na]+:333.1379；Found:333.1387。
本实施例制备化合物3bf-1:淡黄色油状物；产率90％；1H NMR(CDCl3,500MHz)δ:1.75(s,4H),2.73-2.75(m,2H),2.89-2.92(m,2H),3.25(d,J＝12.5Hz,1H),3.43(d,J＝12.5Hz,1H),6.63(d,J＝8.0Hz,1H),6.71(d,J＝8.0Hz,2H),7.02-7.05(m,1H),7.08(d,J＝8.0Hz,2H),7.13-7.16(m,1H),7.36(d,J＝7.5Hz,1H),8.54(br s,1H)；13C NMR(CDCl3,125MHz)δ:23.3,41.9,47.0,70.1,109.9,120.6,122.3,124.9,128.8,129.5,130.6,132.0,133.9,140.6,179.4；HRMS(ESI-TOF)m/z:Calcd.for C19H19BrN2NaO[M+Na]+:393.0578；Found:393.0571。
本实施例制备化合物3bi-1:淡黄色油状物；1H NMR(CDCl3,500MHz)δ:1.76(s,4H),2.74-2.77(m,2H),2.92-2.94(m,2H),3.26(d,J＝13.0Hz,1H),3.44(d,J＝12.5Hz,1H),6.63(d,J＝7.5 Hz,1H),6.81-6.87(m,2H),6.96(s,1H),7.04-7.07(m,1H),7.14-7.17(m,2H),7.36(d,J＝7.5 Hz,1H),8.11(br s,1H)；13C NMR(CDCl3,125 MHz)δ:23.3,42.1,47.0,69.9,109.7,121.4,122.3,125.0,128.8,129.0,129.4,129.5,133.2,137.3,140.4,179.0；HRMS(ESI-TOF)m/z:Calcd.for C19H19BrN2NaO[M+Na]+:393.0578；Found:393.0582。

Claims (4)

1.一种3-叔胺四取代氧化吲哚化合物，其特征在于：该化合物具有如通式(Ⅰ)所示的结构：
式(I)中，R为苄基或取代的苄基；Y为C或氧或硫；n为1或2。
2.一种如权利要求1所述的3-叔胺四取代氧化吲哚化合物的制备方法，其特征在于：将各种取代的3-卤氧化吲哚，以无机碱为催化剂，直接以二级环胺作溶剂和反应底物在加温条件下发生3-叔胺基化反应，获得3-叔胺四取代氧化吲哚化合物。
合成路线如下：
反应机理如下：
其中，R为苄基或取代的苄基；Y为C或氧或硫；n为1或2；X为氯或溴。
3.根据权利要求2所述的3-叔胺四取代氧化吲哚化合物的制备方法，其特征在于：所述的无机碱为碳酸钠、碳酸钾、磷酸钠或磷酸钾。
4.根据权利要求2所述的3-叔胺四取代氧化吲哚化合物的制备方法，其特征在于：所述的反应温度为50-100℃。
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Citations (4)

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Publication number Priority date Publication date Assignee Title
CN101203489A (zh) * 2005-06-24 2008-06-18 霍夫曼-拉罗奇有限公司 羟吲哚衍生物
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CN101203489A (zh) * 2005-06-24 2008-06-18 霍夫曼-拉罗奇有限公司 羟吲哚衍生物
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