3‑烷氧基季碳氧化吲哚及其制备方法与流程

本发明涉及化学技术领域，尤其是一种3-烷氧基季碳氧化吲哚及其制备方法。

背景技术：

3-羟基季碳氧化吲哚骨架广泛存在于许多具有重要生物活性的吲哚生物碱或药物分子中，例如天然产物分子和药物活性分子maremycin，convolutamydine，donaxaridine,cpc-1以及sm-130686包含3-羟基季碳氧化吲哚骨架，具有显著的生物活性(如图7所示)。在这个背景下，鉴于含3-羟基季碳氧化吲哚骨架天然产物具有潜在的生物活性，因此，合成一系列具有3-烷氧基季碳氧化吲哚化合物可能会产生一系列结构和活性上有意义的新化合物分子，它们的合成可以为生物活性筛选提供化合物源，对寻找新型的先导化合物具有重要的意义。

技术实现要素：

本发明的目的是：提供一种3-烷氧基季碳氧化吲哚及其制备方法，它是一类重要的医药中间体和药物类似物，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-烷氧基季碳氧化吲哚，该化合物具有如下通式(i)的结构：

式中，r¹为苯环上不同取代的苄基；r²为氢或卤素；r³为烷基。

3-烷氧基季碳氧化吲哚的制备方法，将3-氯季碳氧化吲哚在醇类溶剂中,加入无机碱或者有机碱,进行3-烷氧基化反应，获得3-烷氧基季碳氧化吲哚。

所述的无机碱包括碳酸钠、碳酸钾、碳酸氢钠、碳酸氢钾、磷酸钾或磷酸氢钾。

所述的有机碱为dbu、dmap、et3n或金鸡纳碱。

所述的碱性催化剂的加入量为3-氯季碳氧化吲哚摩尔量的1-100％。

所述的醇类溶剂为甲醇、乙醇、丙醇、异丙醇、正丁醇或苄醇。

3-氯季碳氧化吲哚在醇类溶剂中反应温度为25至100℃，反应时间为3-10小时。

本发明的反应原理如下：

其中，r¹，r²，r³如上所述。cat.为碱性催化剂。

通过采用上述技术方案，以相应的3-氯季碳氧化吲哚在醇类溶剂中,加入无机碱或者有机碱,进行3-烷氧基化反应，获得3-烷氧基季碳氧化吲哚。它是一类重要的医药中间体和药物类似物，对药物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，可以在各种有机溶剂中进行，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1-6为本发明的实施例化合物3aa-3ca的核磁共振谱图；

附图7为本发明的技术背景说明图；

附图8为本发明的化合物的单晶图。

具体实施方式

本发明的实施例1：

3-烷氧基季碳氧化吲哚3aa的制备，在圆底烧瓶中，依次加入3-氯季碳氧化吲哚1a(0.4mmol)，4.0ml甲醇2a，20mol％na2co3(8.5mg,0.08mmol)，充分搅拌，室温反应8小时。减压蒸馏除掉溶剂，残留油状物硅胶柱层析(300-400目)分离(石油醚：乙酸乙酯＝3：1)，得到淡黄色固体3aa，熔点：120.3-122.5℃；核磁共振和高分辨质谱测试结果如下：¹hnmr(cdcl3,400mhz)δ:3.08(s,3h),3.11(d,j＝12.8hz,1h),3.32(d,j＝12.8hz,1h),6.80-6.83(m,1h),6.93-6.96(m,2h),7.02-7.11(m,5h),7.22-7.26(m,1h),9.13(brs,1h)；¹³cnmr(cdcl3,100mhz)δ:43.6,5.3.3,84.2,110.4,122.6,125.3,126.3,126.7,127.6,129.8,130.6,133.9,141.2,178.6；hrms(esi-tof)m/z:calcd.forc16h15nnao2[m+na]⁺:276.1000；found:276.1004。

化合物3ba～3jf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3ba～3jf，反应产率见表1至表3，但需强调的是本发明的化合物不限于表1至表3所表示的内容。

表1：3-烷氧基季碳氧化吲哚的化学结构

表2：3-烷氧基季碳氧化吲哚的化学结构

表:3：3-烷氧基季碳氧化吲哚的化学结构

本实施例制备化合物3ba：淡黄色固体，熔点：142.3-144.1℃；核磁共振和高分辨质谱测试结果如下：¹hnmr(cdcl3,400mhz)δ:3.03(d,j＝12.8hz,1h),3.05(s,3h),3.23(d,j＝12.8hz,1h),3.66(s,3h),6.57-6.61(m,2h),6.79-6.85(m,3h),7.01-7.03(m,2h),7.20-7.25(m,1h),8.98(brs,1h)；¹³cnmr(cdcl3,100mhz)δ:42.9,53.4,55.1,84.4,110.5,113.1,122.7,125.4,126.0,126.6,129.9,131.7,141.4,158.5,178.8；hrms(esi-tof)m/z:calcd.forc17h17nnao3[m+na]⁺:306.1106；found:306.1107.

本实施例制备化合物3ca：淡黄色固体，熔点：130.7-134.2℃；核磁共振和高分辨质谱测试结果如下：¹hnmr(cdcl3,400mhz)δ:2.13(s,3h),2.97-3.01(m,4h),3.19(d,j＝12.8hz,1h),6.72-6.81(m,5h),6.94-6.99(m,2h),7.13-7.18(m,1h),8.94(brs,1h)；¹³cnmr(cdcl3,100mhz)δ:21.0,43.2,53.2,84.2,110.4,122.5,125.3,126.5,128.3,129.7,130.4,130.7,136.2,141.2,178.7；hrms(esi-tof)m/z:calcd.forc17h17nnao2[m+na]⁺:290.1157；found:290.1154.

本实施例制备化合物3da：淡黄色固体，熔点：120.3-122.4℃；核磁共振和高分辨质谱测试结果如下：¹hnmr(cdcl3,400mhz)δ:3.05(d,j＝13.2hz,1h),3.08(s,3h),3.26(d,j＝13.2hz,1h),6.81-6.84(m,3h),7.03-7.06(m,2h),7.20-7.26(m,3h),8.82(brs,1h)；¹³cnmr(cdcl3,100mhz)δ:43.0,53.3,83.8,110.5,121.0,122.7,125.2,126.0,130.0,130.8,132.3,132.9,141.0,178.2；hrms(esi-tof)m/z:calcd.forc16h14brnnao2[m+na]⁺:354.0106；found:354.0106.

本实施例制备化合物3ea：淡黄色固体，熔点：184.5-187.1℃；核磁共振和高分辨质谱测试结果如下：¹hnmr(cdcl3,400mhz)δ:3.09(s,3h),3.36(d,j＝11.2hz,1h),3.48(d,j＝11.2hz,1h),6.68(d,j＝6.0hz,1h),6.89-6.95(m,2h),7.05-7.09(m,1h),7.20-7.27(m,2h),7.40-7.42(m,1h),7.48-7.50(m,1h),9.32(brs,1h)；¹³cnmr(cdcl3,100mhz)δ:42.0,53.2,83.2,110.5,122.6,125.6,126.8,128.5,129.8,132.4,132.8,134.4,140.9,179.0；hrms(esi-tof)m/z:calcd.forc16h14brnnao2[m+na]⁺:354.0106；found:354.0105.

本实施例制备化合物3fa：淡黄色固体，熔点：138.2-139.8℃；核磁共振和高分辨质谱测试结果如下：¹hnmr(cdcl3,400mhz)δ:3.09(s,3h),3.35(d,j＝13.5hz,1h),3.47(d,j＝13.5hz,1h),6.77(d,j＝7.2hz,1h),6.89-6.97(m,2h),7.13-7.26(m,4h),7.42-7.44(m,1h),9.40(brs,1h)；¹³cnmr(cdcl3,100mhz)δ:39.4,53.2,83.3,110.4,122.6,125.5,125.9,126.2,128.3,129.1,129.8,132.5,132.7,135.3,140.5,141.0,179.0；hrms(esi-tof)m/z:calcd.forc16h14clnnao2[m+na]⁺:310.0611；found:310.0614.

本实施例制备化合物3ga：淡黄色固体，熔点：125.2-127.3℃；核磁共振和高分辨质谱测试结果如下：¹hnmr(cdcl3,400mhz)δ:3.05(d,j＝12.8hz,1h),3.08(s,3h),3.27(d,j＝12.8hz,1h),6.83(d,j＝7.6hz,1h),6.88(d,j＝8.4hz,2h),7.02-7.08(m,4h),7.24-7.28(m,1h),8.93(brs,1h)；¹³cnmr(cdcl3,100mhz)δ:42.9,53.3,83.9,110.5,122.8,125.3,126.1,127.8,130.0,131.9,132.4,132.8,141.1,178.3；hrms(esi-tof)m/z:calcd.forc16h14clnnao2[m+na]⁺:310.0611；found:310.0610.

本实施例制备化合物3ha：淡黄色固体，熔点：135.7-138.2℃；核磁共振和高分辨质谱测试结果如下：¹hnmr(cdcl3,500mhz)δ:3.07(d,j＝13.5hz,1h),3.09(s,3h),3.31(d,j＝13.5hz,1h),6.70-6.75(m,2h),6.83-6.85(m,2h),6.98-7.06(m,3h),7.24-7.27(m,1h),9.12(brs,1h)；¹³cnmr(cdcl3,125mhz)δ:43.2,53.3,83.8,110.5,110.6,113.7(d,jcf＝20.8hz),117.4(d,jcf＝21.3hz),122.7,125.3,126.0,126.3,126.4,128.9,129.0,130.0,136.5,136.6,141.1,141.2,162.1(d,jcf＝245.8hz),178.5；hrms(esi-tof)m/z:calcd.forc16h14fnnao2[m+na]⁺:294.0906；found:294.0908.

本实施例制备化合物3ia：淡黄色固体，熔点：130.4-133.3℃；核磁共振和高分辨质谱测试结果如下：¹hnmr(cdcl3,400mhz)δ:3.00(s,3h),3.03(d,j＝12.8hz,1h),3.21(d,j＝12.8hz,1h),6.66(d,j＝8.4hz,1h),6.87-6.92(m,3h),7.01-7.08(m,3h),7.13-7.19(m,1h),8.83(brs,1h)；¹³cnmr(cdcl3,100mhz)δ:43.6,53.5,84.3,111.4,125.6,127.0,127.8,128.2,128.3,129.8,130.5,133.4,139.6,178.2；hrms(esi-tof)m/z:calcd.forc16h14clnnao2[m+na]⁺:310.0611；found:310.0611.

本实施例制备化合物3ja：淡黄色固体，熔点：198.4-201.9℃；核磁共振和高分辨质谱测试结果如下：¹hnmr(dmso-d6,400mhz)δ:2.91(s,3h),3.00(d,j＝12.8hz,1h),3.20(d,j＝12.8hz,1h),6.66(s,1h),6.67-6.90(m,2h),7.03(d,j＝2.0hz,1h),7.09-7.13(m,4h),10.5(brs,1h)；¹³cnmr(dmso-d6,100mhz)δ:42.3,52.3,83.1,109.9,121.5,125.0,126.6,126.8,127.7,130.3,134.0,134.1,143.9,176.2；hrms(esi-tof)m/z:calcd.forc16h14clnnao2[m+na]⁺:310.0611；found:310.0611.

本实施例制备化合物3ab：淡黄色固体，熔点：112.0-113.8℃；核磁共振和高分辨质谱测试结果如下：¹hnmr(cdcl3,400mhz)δ:1.14-1.18(m,3h),3.10-3.15(m,2h),3.22-3.26(m,1h),3.31(d,j＝12.8hz,1h),6.78(d,j＝7.6hz,1h),6.92-6.93(m,2h),6.94-7.10(m,5h),7.20-7.26(m,1h),9.01(brs,1h)；¹³cnmr(cdcl3,100mhz)δ:15.3,43.8,61.2,83.6,110.3,122.5,125.1,126.7,127.1,127.6,129.6,130.5,134.0,141.0,179.0；hrms(esi-tof)m/z:calcd.forc17h17nnao2[m+na]⁺:290.1157；found:290.1154.

本实施例制备化合物3bb：淡黄色固体，熔点：151.2-153.1℃；核磁共振和高分辨质谱测试结果如下：¹hnmr(cdcl3,400mhz)δ:1.12-1.16(m,3h),3.02-3.12(m,2h),3.19-3.26(m,2h),3.65(s,3h),6.56-6.58(m,2h),6.76-6.84(m,3h),7.01-7.06(m,2h),7.18-7.25(m,1h),8.93(brs,1h)；¹³cnmr(cdcl3,100mhz)δ:15.5,43.1,55.1,61.3,83.8,110.4,113.1,122.6,125.2,126.1,127.5,129.7,131.6,141.2,158.4,179.1；hrms(esi-tof)m/z:calcd.forc18h19nnao3[m+na]⁺:320.1263；found:320.1263.

本实施例制备化合物3cb：淡黄色固体，熔点：138.8-141.9℃；核磁共振和高分辨质谱测试结果如下：¹hnmr(cdcl3,400mhz)δ:1.07-1.10(m,3h),2.13(s,3h),2.99-3.07(m,2h),3.14-3.22(m,2h),6.69-6.79(m,5h),6.94-7.01(m,2h),7.12-7.18(m,1h),8.82(brs,1h)；¹³cnmr(cdcl3,100mhz)δ:15.3,21.0,43.4,61.1,83.6,110.2,122.5,125.1,127.3,128.3,129.6,130.4,130.8,136.1,141.0,178.9；hrms(esi-tof)m/z:calcd.forc18h19nnao2[m+na]⁺:304.1313；found:304.1315.

本实施例制备化合物3db：淡黄色固体，熔点：142.1-144.6℃；核磁共振和高分辨质谱测试结果如下：¹hnmr(cdcl3,400mhz)δ:1.15-1.18(m,3h),3.04(d,j＝13.2hz,1h),3.11-3.15(m,1h),3.22-3.28(m,2h),6.78-6.84(m,3h),7.03-7.05(m,2h),7.18-7.27(m,3h),8.82(brs,1h)；¹³cnmr(cdcl3,100mhz)δ:15.3,43.2,61.3,83.2,110.4,120.9,122.7,125.1,126.8,129.8,130.7,132.3,133.0,140.8,178.6；hrms(esi-tof)m/z:calcd.forc17h16brnnao2[m+na]⁺:368.0262；found:368.0265.

本实施例制备化合物3eb：淡黄色固体，熔点：185.1-186.2℃；核磁共振和高分辨质谱测试结果如下：¹hnmr(cdcl3,400mhz)δ:1.14-1.18(m,3h),3.07-3.11(m,1h),3.23-3.28(m,1h),3.32(d,j＝13.6hz,1h),3.47(d,j＝13.6hz,1h),6.65(d,j＝7.2hz,1h),6.86-6.92(m,2h),7.05-7.07(m,1h),7.18-7.25(m,2h),7.38-7.40(m,1h),7.49-7.52(m,1h)；¹³cnmr(cdcl3,100mhz)δ:15.4,42.2,61.2,82.7,110.5,122.6,125.6,126.5,126.7,126.9,128.6,129.7,132.4,132.9,134.7,140.9,179.4；hrms(esi-tof)m/z:calcd.forc17h16brnnao2[m+na]⁺:368.0262；found:368.0262.

本实施例制备化合物3fb：淡黄色固体，熔点：207.1-209.2℃；核磁共振和高分辨质谱测试结果如下：¹hnmr(dmso-d6,400mhz)δ:1.01-1.05(m,3h),2.91-2.95(m,1h),3.05-3.08(m,1h),3.14(d,j＝12.8hz,1h),3.32(d,j＝12.8hz,1h),6.72(d,j＝7.8hz,1h),6.80-6.87(m,2h),7.14-7.28(m,5h),10.5(brs,1h)；¹³cnmr(dmso-d6,100mhz)δ:15.3,40.1,60.0,82.0,109.8,121.5,124.8,126.5,128.6,129.0,129.7,132.2,132.5,142.0,176.7；hrms(esi-tof)m/z:calcd.forc17h16clnnao2[m+na]⁺:324.0767；found:324.0769.

本实施例制备化合物3gb：淡黄色固体，熔点：154.1-156.2℃；核磁共振和高分辨质谱测试结果如下：¹hnmr(cdcl3,400mhz)δ:1.14-1.18(m,3h),3.06(d,j＝12.8hz,1h),3.11-3.15(m,1h),3.21-3.25(m,1h),3.28(d,j＝12.8hz,1h),6.81(d,j＝8.0hz,1h),6.88(d,j＝8.4hz,2h),7.02-7.05(m,4h),7.22-7.27(m,1h),9.04(brs,1h)；¹³cnmr(cdcl3,100mhz)δ:15.3,43.1,61.3,83.3,110.4,122.7,125.1,126.9,127.7,129.8,131.9,132.5,132.7,140.9,178.7；hrms(esi-tof)m/z:calcd.forc17h16clnnao2[m+na]⁺:324.0767；found:324.0766.

本实施例制备化合物3hb：淡黄色固体，熔点：118.3-119.8℃；核磁共振和高分辨质谱测试结果如下：¹hnmr(cdcl3,500mhz)δ:1.16-1.19(m,3h),3.08(d,j＝13.0hz,1h),3.12-3.15(m,1h),3.24-3.27(m,1h),3.31(d,j＝13.0hz,1h),6.69-6.75(m,2h),6.80-6.83(m,2h),7.00-7.05(m,3h),7.22-7.26(m,1h),9.10(brs,1h)；¹³cnmr(cdcl3,125mhz)δ:15.3,43.4,61.2,83.2,110.4,110.5,113.6,113.7,117.4(d,jcf＝21.3hz),122.7,125.1,126.3,126.4,126.8,128.9(d,jcf＝8.8hz),129.8,136.6(d,jcf＝7.5hz),140.9,162.1(d,jcf＝243.8hz),178.7；hrms(esi-tof)m/z:calcd.forc17h16fnnao2[m+na]⁺:308.1063；found:308.1067.

本实施例制备化合物3ac：淡黄色固体，熔点：146.1-148.3℃；核磁共振和高分辨质谱测试结果如下：¹hnmr(cdcl3,400mhz)δ:0.84-0.88(m,3h),1.54-1.60(m,2h),2.95-3.01(m,1h),3.08(d,j＝12.8hz,1h),3.15-3.20(m,1h),3.33(d,j＝12.8hz,1h),6.78(d,j＝7.6hz,1h),6.96-7.13(m,7h),7.19-7.26(m,1h),8.90(brs,1h)；¹³cnmr(cdcl3,100mhz)δ:10.5,23.1,43.8,67.2,83.4,110.2,122.5,125.3,126.7,127.2,127.6,129.6,130.7,134.1,140.9,178.9；hrms(esi-tof)m/z:calcd.forc18h19nnao2[m+na]⁺:304.1313；found:304.1315.

本实施例制备化合物3bc：淡黄色固体，熔点：145.5-146.9℃；核磁共振和高分辨质谱测试结果如下：¹hnmr(cdcl3,400mhz)δ:0.81-0.85(m,3h),1.52-1.56(m,2h),2.94-3.02(m,2h),3.12-3.15(m,1h),3.25(d,j＝12.8hz,1h),3.66(s,3h),6.57-6.60(m,2h),6.78(d,j＝7.6hz,1h),6.84-6.87(m,2h),6.97-7.00(m,2h),7.19-7.25(m,1h),8.99(brs,1h)；¹³cnmr(cdcl3,100mhz)δ:10.7,23.2,43.0,55.1,67.3,83.6,110.4,113.1,122.6,125.4,126.2,127.5,129.7,131.7,141.2,158.4,179.3；hrms(esi-tof)m/z:calcd.forc19h21nnao3[m+na]⁺:334.1419；found:334.1415.

本实施例制备化合物3cc：淡黄色固体，熔点：75.1-76.8℃；核磁共振和高分辨质谱测试结果如下：¹hnmr(cdcl3,400mhz)δ:0.76-0.80(m,3h),1.46-1.53(m,2h),2.15(s,3h),2.89-2.93(m,1h),2.98(d,j＝12.8hz,1h),3.08-3.11(m,1h),3.21(d,j＝12.8hz,1h),6.68(d,j＝7.6hz,1h),6.76-6.82(m,4h),6.92-6.97(m,2h),7.12-7.19(m,1h),8.41(brs,1h)；¹³cnmr(cdcl3,100mhz)δ:10.5,21.0,23.1,43.4,67.2,83.3,110.1,122.4,125.3,127.4,128.3,129.5,130.5,130.9,136.1,140.9,178.7；hrms(esi-tof)m/z:calcd.forc19h21nnao2[m+na]⁺:318.1470；found:318.1472.

本实施例制备化合物3dc：淡黄色固体，熔点：143.3-144.8℃；核磁共振和高分辨质谱测试结果如下：¹hnmr(cdcl3,400mhz)δ:0.84-0.87(m,3h),1.53-1.59(m,2h),2.95-3.02(m,2h),3.14-3.19(m,1h),3.27(d,j＝12.8hz,1h),6.81-6.86(m,3h),6.94-6.96(m,1h),7.01-7.04(m,1h),7.20-7.24(m,3h),8.88(brs,1h)；¹³cnmr(cdcl3,100mhz)δ:10.5,23.0,43.1,67.2,83.0,110.4,120.9,122.6,125.2,126.9,129.8,130.7,132.4,133.2,140.8,178.7；hrms(esi-tof)m/z:calcd.forc18h18brnnao2[m+na]⁺:382.0419；found:382.0417.

本实施例制备化合物3ec：淡黄色固体，熔点：153.1-154.9℃；核磁共振和高分辨质谱测试结果如下：¹hnmr(cdcl3,400mhz)δ:0.85-0.88(m,3h),1.54-1.62(m,2h),2.95(d,j＝6.0hz,1h),3.21(d,j＝6.4hz,1h),3.32(d,j＝11.2hz,1h),3.48(d,j＝11.2hz,1h),6.59(d,j＝6.0hz,1h),6.89-6.92(m,2h),7.07-7.09(m,1h),7.21-7.26(m,2h),7.41(d,j＝6.4hz,1h),7.56(d,j＝6.0hz,1h),9.22(brs,1h)；¹³cnmr(cdcl3,100mhz)δ:10.6,23.1,42.1,67.0,82.3,110.3,122.5,125.5,126.5,126.6,126.7,128.4,129.6,132.3,133.0,134.7,140.7,179.2；hrms(esi-tof)m/z:calcd.forc18h18brnnao2[m+na]⁺:382.0419；found:382.0421.

本实施例制备化合物3fc：淡黄色固体，熔点：160.3-161.9℃；核磁共振和高分辨质谱测试结果如下：¹hnmr(cdcl3,400mhz)δ:0.85-0.88(m,3h),1.56-1.62(m,2h),2.94-2.98(m,1h),3.18-3.22(m,1h),3.33(d,j＝13.6hz,1h),3.46(d,j＝13.6hz,1h),6.69(d,j＝7.2hz,1h),6.86-6.94(m,2h),7.13-7.26(m,4h),7.51(d,j＝4.0hz,1h),9.15(brs,1h)；¹³cnmr(cdcl3,100mhz)δ:10.6,23.1,39.6,67.1,82.4,110.2,122.5,125.4,126.0,126.7,128.2,129.0,129.6,132.8,135.3,140.8,179.2；hrms(esi-tof)m/z:calcd.forc18h18clnnao2[m+na]⁺:338.0924；found:338.0924.

本实施例制备化合物3gc：淡黄色固体，熔点：158.1-161.2℃；核磁共振和高分辨质谱测试结果如下：¹hnmr(cdcl3,400mhz)δ:0.84-0.87(m,3h),1.53-1.60(m,2h),2.96-3.00(m,1h),3.03(d,j＝12.8hz,1h),3.14-3.18(m,1h),3.29(d,j＝12.8hz,1h),6.81(d,j＝7.6hz,1h),6.89-6.97(m,3h),7.01-7.07(m,3h),7.22-7.26(m,1h),8.90(brs,1h)；¹³cnmr(cdcl3,100mhz)δ:10.5,23.0,43.1,67.3,83.0,110.3,122.6,125.2,126.9,127.7,129.8,132.0,132.7,140.8,178.7；hrms(esi-tof)m/z:calcd.forc18h18clnnao2[m+na]⁺:338.0924；found:338.0927.

本实施例制备化合物3dd：淡黄色固体，熔点：148.1-150.1℃；核磁共振和高分辨质谱测试结果如下：¹hnmr(cdcl3,500mhz)δ:1.01(d,j＝6.5hz,3h),1.10(d,j＝6.0hz,3h),2.97(d,j＝13.0hz,1h),3.23(d,j＝13.0hz,1h),6.78-6.83(m,3h),6.98-7.02(m,2h),7.19-7.27(m,3h),8.57(brs,1h)；¹³cnmr(cdcl3,125mhz)δ:23.1,24.1,43.8,69.5,82.7,110.3,120.9,122.4,125.6,127.3,129.8,130.6,132.4,133.2,140.6,179.3；hrms(esi-tof)m/z:calcd.forc18h18brnnao2[m+na]⁺:382.0419；found:382.0419.

本实施例制备化合物3ed：淡黄色固体，熔点：182.0-183.3℃；核磁共振和高分辨质谱测试结果如下：¹hnmr(cdcl3,400mhz)δ:0.99(d,j＝6.0hz,3h),1.10(d,j＝6.0hz,3h),3.24(d,j＝14.0hz,1h),3.40-3.44(m,2h),6.53(d,j＝7.2hz,1h),6.84-6.89(m,2h),7.03-7.08(m,1h),7.18-7.25(m,2h),7.37-7.41(m,1h),7.55-7.57(m,1h),9.16(brs,1h)；¹³cnmr(cdcl3,100mhz)δ:23.2,24.0,42.7,69.3,82.1,110.5,122.4,126.1,126.7,126.8,126.9,128.5,129.7,132.3,133.1,134.9,140.6,180.4；hrms(esi-tof)m/z:calcd.forc18h18brnnao2[m+na]⁺:382.0419；found:382.0422.

本实施例制备化合物3fd：淡黄色固体，熔点：197.2-198.7℃；核磁共振和高分辨质谱测试结果如下：¹hnmr(cdcl3,400mhz)δ:1.01(d,j＝6.0hz,3h),1.12(d,j＝6.0hz,3h),3.27(d,j＝13.6hz,1h),3.40-3.45(m,2h),6.66(d,j＝7.2hz,1h),6.87-6.92(m,2h),7.12-7.26(m,4h),7.49-7.52(m,1h),9.16(brs,1h)；¹³cnmr(cdcl3,100mhz)δ:23.1,24.0,40.1,69.2,82.1,110.3,122.2,125.9,126.0,127.0,128.1,128.9,129.6,132.9,135.4,140.5,180.1；hrms(esi-tof)m/z:calcd.forc18h18clnnao2[m+na]⁺:338.0924；found:338.0925.

本实施例制备化合物3gd：淡黄色固体，熔点：198.2-201.3℃；核磁共振和高分辨质谱测试结果如下：¹hnmr(cdcl3,400mhz)δ:1.01(d,j＝6.4hz,3h),1.08(d,j＝6.0hz,3h),2.98(d,j＝12.8hz,1h),3.25(d,j＝12.8hz,1h),3.38-3.45(m,1h),6.81(d,j＝7.6hz,1h),6.86-6.89(m,2h),6.97-7.04(m,4h),7.22-7.27(m,1h),8.97(brs,1h)；¹³cnmr(cdcl3,100mhz)δ:23.1,24.1,43.7,69.5,82.8,110.4,122.4,125.6,127.3,127.7,129.8,132.0,132.6,132.7,140.6,179.6；hrms(esi-tof)m/z:calcd.forc18h18clnnao2[m+na]⁺:338.0924；found:338.0926.

本实施例制备化合物3ae：淡黄色固体，熔点：125.5-126.7℃；核磁共振和高分辨质谱测试结果如下：¹hnmr(cdcl3,400mhz)δ:0.82-0.85(m,3h),1.28-1.36(m,2h),1.49-1.54(m,2h),3.01-3.09(m,2h),3.16-3.20(m,1h),3.32(d,j＝12.8hz,1h),6.78-6.81(m,1h),6.95-7.11(m,7h),7.19-7.26(m,1h),9.01(brs,1h)；¹³cnmr(cdcl3,100mhz)δ:13.8,19.1,31.8,43.8,65.3,83.4,110.3,122.4,125.2,126.7,127.2,127.5,129.6,130.6,134.1,141.0,179.1；hrms(esi-tof)m/z:calcd.forc19h21nnao2[m+na]⁺:318.1470；found:318.1473.

本实施例制备化合物3be：淡黄色固体，熔点：139.5-141.7℃；核磁共振和高分辨质谱测试结果如下：¹hnmr(cdcl3,400mhz)δ:0.81-0.85(m,3h),1.28-1.34(m,2h),1.48-1.52(m,2h),6.59(d,j＝8.4hz,2h),6.80(d,j＝7.6hz,1h),6.87(d,j＝8.8hz,2h),6.97-7.04(m,2h),7.20-7.24(m,1h),9.08(brs,1h)；¹³cnmr(cdcl3,100mhz)δ:13.8,19.1,31.8,42.9,54.9,65.2,83.5,110.3,112.9,122.4,125.2,126.1,127.3,129.5,131.5,141.0,158.2,179.1；hrms(esi-tof)m/z:calcd.forc20h23nnao3[m+na]⁺:348.1576；found:348.1576.

本实施例制备化合物3ce：淡黄色固体，熔点：105.1-107.7℃；核磁共振和高分辨质谱测试结果如下：¹hnmr(cdcl3,400mhz)δ:0.74-0.78(m,3h),1.22-1.25(m,2h),1.43-1.48(m,2h),2.13(s,3h),2.93-2.98(m,2h),3.10-3.13(m,1h),3.20(d,j＝13.2hz,1h),6.71(d,j＝8.0hz,1h),6.75-6.81(m,4h),6.90-6.94(m,2h),7.12-7.18(m,1h),8.87(brs,1h)；¹³cnmr(cdcl3,100mhz)δ:13.8,19.1,21.0,31.9,43.3,65.2,83.4,110.2,122.4,125.2,127.3,128.2,129.5,130.5,130.9,136.1,141.0,179.0；hrms(esi-tof)m/z:calcd.forc20h23nnao2[m+na]⁺:332.1626；found:332.1629.

本实施例制备化合物3de：淡黄色固体，熔点：136.0-138.1℃；核磁共振和高分辨质谱测试结果如下：¹hnmr(cdcl3,400mhz)δ:0.82-0.85(m,3h),1.30-1.35(m,2h),1.48-1.54(m,2h),2.99-3.03(m,2h),3.17-3.19(m,1h),3.27(d,j＝13.0hz,1h),6.80-6.86(m,3h),6.94-6.96(m,1h),7.01-7.04(m,1h),7.20-7.27(m,3h),8.93(brs,1h)；¹³cnmr(cdcl3,100mhz)δ:13.8,19.1,31.8,43.1,65.3,83.0,110.4,120.9,122.6,125.2,126.9,129.8,130.7,132.4,133.2,140.8,178.7；hrms(esi-tof)m/z:calcd.forc19h20brnnao2[m+na]⁺:396.0575；found:396.0578.

本实施例制备化合物3ee：淡黄色固体，熔点：98.9-99.3℃；核磁共振和高分辨质谱测试结果如下：¹hnmr(cdcl3,400mhz)δ:0.82-0.85(m,3h),1.25-1.36(m,2h),1.45-1.51(m,2h),3.00-3.01(m,1h),3.22-3.24(m,1h),3.32(d,j＝11.2hz,1h),3.48(d,j＝11.2hz,1h),6.59(d,j＝6.0hz,1h),6.89-6.92(m,2h),7.07-7.08(m,1h),7.20-7.25(m,2h),7.40-7.42(m,1h),7.55(d,j＝6.0hz,1h),9.55(brs,1h)；¹³cnmr(cdcl3,100mhz)δ:13.8,19.2,31.8,42.1,65.1,82.4,110.4,122.4,125.4,126.5,126.6,126.7,128.4,129.5,132.3,132.9,134.7,140.8,179.4；hrms(esi-tof)m/z:calcd.forc19h20brnnao2[m+na]⁺:396.0575；found:396.0575.

本实施例制备化合物3fe：淡黄色固体，熔点：142.1-144.0℃；核磁共振和高分辨质谱测试结果如下：¹hnmr(cdcl3,400mhz)δ:0.82-0.86(m,3h),1.33-1.38(m,2h),1.49-1.57(m,2h),2.97-3.03(m,1h),3.20-3.25(m,1h),3.32(d,j＝13.6hz,1h),3.46(d,j＝13.6hz,1h),6.69(d,j＝7.6hz,1h),6.87-6.94(m,2h),7.13-7.26(m,4h),7.47-7.50(m,1h),9.29(brs,1h)；¹³cnmr(cdcl3,100mhz)δ:13.8,19.2,31.8,39.6,65.1,82.5,110.3,122.5,125.4,126.0,126.7,128.2,129.0,129.6,132.8,132.9,135.3,140.7,179.2；hrms(esi-tof)m/z:calcd.forc19h20clnnao2[m+na]⁺:352.1080；found:352.1082.

本实施例制备化合物3ge：淡黄色固体，熔点：142.1-144.3℃；核磁共振和高分辨质谱测试结果如下：¹hnmr(cdcl3,400mhz)δ:0.81-0.85(m,3h),1.30-1.34(m,2h),1.50-1.54(m,2h),3.00-3.05(m,2h),3.16-3.21(m,1h),3.28(d,j＝12.8hz,1h),6.80-6.83(m,1h),6.89-6.96(m,3h),7.01-7.06(m,3h),7.21-7.27(m,1h),9.09(brs,1h)；¹³cnmr(cdcl3,100mhz)δ:13.7,19.1,31.8,43.1,65.3,83.1,110.4,122.6,125.1,126.9,127.7,129.7,132.0,132.7,140.9,178.8；hrms(esi-tof)m/z:calcd.forc19h20clnnao2[m+na]⁺:352.1080；found:352.1083.

本实施例制备化合物3he：淡黄色固体，熔点：129.0-131.1℃；核磁共振和高分辨质谱测试结果如下：¹hnmr(cdcl3,500mhz)δ:0.82-0.86(m,3h),1.26-1.35(m,2h),1.45-1.57(m,2h),3.02-3.05(m,2h),3.19-3.22(m,1h),3.32(d,j＝13.5hz,1h),6.72-6.76(m,2h),6.80-6.84(m,2h),6.91-6.95(m,1h),7.01-7.05(m,2h),7.22-7.26(m,1h),9.18(brs,1h)；¹³cnmr(cdcl3,125mhz)δ:13.7,19.1,31.8,43.4,65.3,83.0,110.4,113.6(d,jcf＝21.1hz),117.4(d,jcf＝21.2hz),122.6,125.1,126.4,126.9,128.8,128.9,129.8,136.7,136.8,140.9,162.1(d,jcf＝243.8hz),178.9；hrms(esi-tof)m/z:calcd.forc19h20fnnao2[m+na]⁺:336.1376；found:336.1377.

本实施例制备化合物3af：淡黄色固体，熔点：168.8-170.3℃；核磁共振和高分辨质谱测试结果如下：¹hnmr(cdcl3,400mhz)δ:3.18(d,j＝12.8hz,1h),3.41(d,j＝12.8hz,1h),4.12(d,j＝8.2hz,1h),4.25(d,j＝12.8hz,1h),6.80(d,j＝8.0hz,1h),6.97-7.10(m,7h),7.21-7.29(m,6h),8.97(brs,1h)；¹³cnmr(cdcl3,100mhz)δ:43.8,67.8,83.8,110.4,122.6,125.4,126.8,127.6,127.7,127.8,128.2,129.9,130.7,133.9,137.5,141.1,178.4；hrms(esi-tof)m/z:calcd.forc22h19nnao2[m+na]⁺:352.1313；found:352.1313.

本实施例制备化合物3bf：淡黄色固体，熔点：218.1-219.8℃；核磁共振和高分辨质谱测试结果如下：¹hnmr(cdcl3,400mhz)δ:3.12(d,j＝13.2hz,1h),3.34(d,j＝13.2hz,1h),3.64(s,3h),4.11(d,j＝10.8hz,1h),4.23(d,j＝10.4hz,1h),6.58-6.61(m,2h),6.79-6.81(m,1h),6.87-6.89(m,2h),7.05-7.10(m,2h),7.22-7.29(m,6h),8.88(brs,1h)；¹³cnmr(cdcl3,100mhz)δ:43.0,55.1,68.0,84.0,110.6,113.2,122.8,125.5,126.0,127.1,127.8,128.0,128.3,130.0,131.8,137.7,141.2,158.5,178.7；hrms(esi-tof)m/z:calcd.forc23h21nnao3[m+na]⁺:382.1419；found:382.1421.

本实施例制备化合物3cf：淡黄色固体，熔点：132.2-134.3℃；核磁共振和高分辨质谱测试结果如下：¹hnmr(cdcl3,400mhz)δ:2.10(s,3h),3.06(d,j＝13.2hz,1h),3.28(d,j＝12.8hz,1h),4.03(d,j＝10.4hz,1h),4.16(d,j＝10.8hz,1h),6.72(d,j＝8.0hz,1h),6.78(s,4h),6.96-7.02(m,2h),7.14-7.20(m,6h),8.93(brs,1h)；¹³cnmr(cdcl3,100mhz)δ:21.0,43.3,67.8,83.8,110.4,122.6,125.3,126.9,127.6,127.8,128.2,128.4,129.8,130.5,130.7,136.2,137.6,141.1,178.5；hrms(esi-tof)m/z:calcd.forc23h21nnao2[m+na]⁺:366.1470；found:366.1474.

本实施例制备化合物3df：淡黄色固体，熔点：201.2-203.2℃；核磁共振和高分辨质谱测试结果如下：¹hnmr(dmso-d6,400mhz)δ:3.08(d,j＝10.0hz,1h),3.27(d,j＝10.0hz,1h),3.99(d,j＝8.4hz,1h),4.12(d,j＝8.4hz,1h),6.71(d,j＝6.0hz,1h),6.86(d,j＝6.4hz,1h),7.19-7.22(m,1h),7.26-7.31(m,9h)；¹³cnmr(dmso-d6,100mhz)δ:41.4,66.1,82.3,109.5,119.5,121.4,124.5,125.6,127.0,127.1,127.7,129.5,130.0,132.0,133.2,137.2,141.8,175.6；hrms(esi-tof)m/z:calcd.forc22h18brnnao2[m+na]⁺:430.0419；found:430.0423.

本实施例制备化合物3ef：淡黄色固体，熔点：158.8-160.1℃；核磁共振和高分辨质谱测试结果如下：¹hnmr(cdcl3,400mhz)δ:3.42(d,j＝14.0hz,1h),3.58(d,j＝14.0hz,1h),4.12(d,j＝10.8hz,1h),4.30(d,j＝10.8hz,1h),6.70(d,j＝7.6hz,1h),6.91-6.95(m,2h),7.07-7.09(m,1h),7.21-7.30(m,7h),7.42(d,j＝8.1hz,1h),7.56(d,j＝8.0hz,1h),9.35(brs,1h)；¹³cnmr(cdcl3,100mhz)δ:42.2,67.8,82.9,110.7,122.8,125.8,126.3,126.6,127.0,127.7,127.8,128.3,128.7,130.0,132.5,133.1,134.6,137.8,141.0,179.0；hrms(esi-tof)m/z:calcd.forc22h18brnnao2[m+na]⁺:430.0419；found:430.0418.

本实施例制备化合物3ff：淡黄色固体，熔点：145.3-147.2℃；核磁共振和高分辨质谱测试结果如下：¹hnmr(cdcl3,400mhz)δ:3.42(d,j＝14.0hz,1h),3.56(d,j＝13.6hz,1h),4.12(d,j＝10.8hz,1h),4.29(d,j＝10.8hz,1h),6.80(d,j＝7.2hz,1h),6.89-6.96(m,2h),7.12-7.15(m,2h),7.20-7.28(m,7h),7.48-7.50(m,1h),9.34(brs,1h)；¹³cnmr(cdcl3,100mhz)δ:39.6,67.7,82.9,110.5,122.6,125.5,126.1,126.3,127.6,128.2,128.3,129.1,129.9,132.6,132.9,135.3,137.6,140.8,178.7；hrms(esi-tof)m/z:calcd.forc22h18clnnao2[m+na]⁺:386.0924；found:386.0925.

本实施例制备化合物3gf：淡黄色固体，熔点：110.3-112.8℃；核磁共振和高分辨质谱测试结果如下：¹hnmr(dmso-d6,400mhz)δ:3.09(d,j＝12.8hz,1h),3.29(d,j＝12.8hz,1h),3.99(d,j＝10.8hz,1h),4.13(d,j＝10.8hz,1h),6.71(d,j＝8.0hz,1h),6.92(d,j＝8.4hz,2h),7.00-7.03(m,1h),7.15-7.30(m,9h),10.5(brs,1h)；¹³cnmr(dmso-d6,100mhz)δ:41.4,66.1,82.4,109.5,121.4,124.5,125.7,127.0,127.1,127.7,129.5,131.0,131.6,132.9,137.2,141.8,175.6；hrms(esi-tof)m/z:calcd.forc22h18clnnao2[m+na]⁺:386.0924；found:386.0924.

本实施例制备化合物3hf：淡黄色固体，熔点：153.2-155.1℃；核磁共振和高分辨质谱测试结果如下：¹hnmr(cdcl3,500mhz)δ:3.16(d,j＝10.4hz,1h),3.39(d,j＝13.4hz,1h),4.13(d,j＝11.0hz,1h),4.27(d,j＝10.5hz,1h),6.72-6.74(m,1h),6.76-6.78(m,1h),6.81-6.84(m,2h),7.04-7.06(m,3h),7.23-7.29(m,6h)；¹³cnmr(cdcl3,125mhz)δ:43.4,67.9,83.4,110.5,113.7(d,jcf＝20.1hz),117.4(d,jcf＝21.3hz),122.8,125.3,126.5,127.7,127.8,128.3,129.0,129.1,130.1,136.5,137.4,141.0,162.1(d,jcf＝243.8hz),178.2；hrms(esi-tof)m/z:calcd.forc22h18fnnao2[m+na]⁺:370.1219；found:370.1221.

本实施例制备化合物3if：淡黄色固体，熔点：217.3-220.5℃；核磁共振和高分辨质谱测试结果如下：¹hnmr(dmso-d6,400mhz)δ:3.09(d,j＝12.4h,1h),3.33(d,j＝12.8hz,1h),4.03(d,j＝10.8hz,1h),4.16(d,j＝10.8hz,1h),6.68(d,j＝8.8hz,1h),6.92-6.95(m,2h),7.11-7.13(m,3h),7.22-7.32(m,7h),10.6(brs,1h)；¹³cnmr(dmso-d6,100mhz)δ:42.4,66.8,83.2,111.3,125.2,125.9,126.8,127.5,127.6,127.7,128.2,128.5,129.7,130.3,133.9,137.6,141.2,176.0；hrms(esi-tof)m/z:calcd.forc22h18clnnao2[m+na]⁺:386.0924；found:386.0926.

本实施例制备化合物3jf：淡黄色固体，熔点：165.1-168.5℃；核磁共振和高分辨质谱测试结果如下：¹hnmr(cdcl3,400mhz)δ:3.04(d,j＝13.2hz,1h),3.31(d,j＝13.2hz,1h),4.01(d,j＝10.8hz,1h),4.16(d,j＝10.8hz,1h),6.75-6.76(m,1h),6.84-6.94(m,4h),7.00-7.06(m,3h),7.16-7.23(m,5h),9.04(brs,1h)；¹³cnmr(cdcl3,100mhz)δ:43.6,67.9,83.4,111.2,122.7,125.1,126.4,127.0,127.8,128.3,130.7,133.6,135.5,137.2,142.1,178.5；hrms(esi-tof)m/z:calcd.forc22h18clnnao2[m+na]⁺:386.0924；found:386.0925.

本发明的实施例2：化合物3aa:在圆底烧瓶中，依次加入3-氯季碳氧化吲哚1a(0.4mmol)，4.0ml甲醇2a，20mol％et3n(8.1mg,0.08mmol)，充分搅拌，室温反应8小时。减压蒸馏除掉溶剂，残留油状物硅胶柱层析(300-400目)分离(石油醚：乙酸乙酯＝8：1)，得到淡黄色固体。产率：89％。

采用本实施例2制备，投料比与化合物3aa相同，可分别得到化合物3ba(产率91％)，化合物3ca(产率88％)，化合物3da(产率89％)，化合物3ea(产率88％)，化合物3fa(产率87％)，化合物3ga(产率92％)，化合物3ha(产率88％)，化合物3ia(产率96％)，化合物3ja(产率87％)，化合物3ab(产率86％)，化合物3bb(产率86％)，化合物3cb(产率88％)，化合物3db(产率86％)，化合物3eb(产率84％)，化合物3fb(产率85％)，化合物3gb(产率83％)，化合物3hb(产率87％)，化合物3ac(产率80％)，化合物3bc(产率85％)，化合物3cc(产率82％)，化合物3dc(产率86％)，化合物3ec(产率80％)，化合物3fc(产率82％)，化合物3gc(产率78％)，化合物3dd(产率77％)，化合物3ed(产率75％)，化合物3fd(产率74％)，化合物3gd(产率70％)，化合物3ae(产率79％)，化合物3be(产率75％)，化合物3ce(产率73％),化合物3de(产率73％)；化合物3ee(产率72％)，化合物3fe(产率73％)，化合物3ge(产率71％)，化合物3he(产率75％)，化合物3af(产率78％)，化合物3bf(产率73％),化合物3cf(产率78％)；化合物3df(产率82％)，化合物3ef(产率83％)，化合物3ff(产率82％)，化合物3gf(产率85％)，化合物3hf(产率83％)，化合物3if(产率85％),化合物3jf(产率88％)。