一种3烷基取代7氮杂吲哚化合物的合成方法.pdf

摘要
申请专利号：	CN201410492337.9	申请日：	2014.09.23
公开号：	CN104193742A	公开日：	2014.12.10
当前法律状态：	驳回	有效性：	无权
法律详情：	发明专利申请公布后的驳回 IPC(主分类):C07D 471/04申请公布日:20141210\|\|\|实质审查的生效IPC(主分类):C07D 471/04申请日:20140923\|\|\|公开
IPC分类号：	C07D471/04	主分类号：	C07D471/04
申请人：	西华师范大学
发明人：	敬林海; 秦大斌; 罗干; 靳伦强
地址：	637002 四川省南充市师大路1号
优先权：
专利代理机构：	北京众合诚成知识产权代理有限公司 11246	代理人：	裴娜
PDF下载：	PDF下载

内容摘要

本发明公开了一种3-烷基取代-7-氮杂吲哚化合物的合成方法，属于有机合成技术领域，本发明首先设计并合成了一系列包含7-氮杂吲哚片段的化合物1，其次，以1作为亲电试剂，在温和条件下与各种各样的亲核试剂(碳亲核试剂、氮亲核试剂、氧亲核试剂以及硫亲核试剂)反应合成出结构多变的3-烷基取代-7-氮杂吲哚化合物。本发明在简单的反应条件下，方便高效地合成了各种结构的3-烷基取代-7-氮杂吲哚化合物。

权利要求书

1.  一种3-烷基取代-7-氮杂吲哚化合物的合成方法，其特征在于：所述合成方法的合成路线如下：

2.  如权利要求1所述的3-烷基取代-7-氮杂吲哚化合物的合成方法，其特征在于：所述合成方法的具体步骤如下：
(a)3-(1-芳砜烷基)-7-氮杂吲哚(1)的合成：
将四甲基胍加入到7-氮杂吲哚的水悬浮液中，四甲基胍与7-氮杂吲哚的摩尔比为10-20:10，7-氮杂吲哚与水的摩尔体积比为10:30-70mmol/mL，然后在20-40℃条件下搅拌5-15min后，加入醛类化合物并在20-40℃下搅拌反应12-24h，醛类化合物与7-氮杂吲哚的摩尔比为5-15:10，然后过滤，滤饼用乙酸乙酯/石油醚重结晶得醇(A)；
将醇(A)加入到乙酸乙酯中，醇(A)与乙酸乙酯的摩尔体积比为10:80-120mmol/mL，醇(A)溶解后加入对甲苯亚磺酸和对甲苯磺酸，对甲苯亚磺酸与醇A的摩尔比为10-15:10，对甲苯磺酸与醇(A)的摩尔比为10-20:10，然后在20-40℃下搅拌反应18-30h后，过滤，滤饼用乙酸乙酯/石油醚重结晶得3-(1-芳砜烷基)-7-氮杂吲哚(1)；
(b)3-烷基取代-7-氮杂吲哚化合物的合成：
往3-(1-芳砜烷基)-7-氮杂吲哚(1)中加入碳酸钾或氢氧化钠，然后再加入亲核试剂，碳酸钾或氢氧化钠与3-(1-芳砜烷基)-7-氮杂吲哚(1)的摩尔比为 10-15:10，亲核试剂与3-(1-芳砜烷基)-7-氮杂吲哚(1)的摩尔比为10-15:10，然后在40-65℃下搅拌反应1-36h，然后使用乙酸乙酯/石油醚进行柱层析得到3-烷基取代-7-氮杂吲哚化合物。

3.  如权利要求2所述的3-烷基取代-7-氮杂吲哚化合物的合成方法，其特征在于：步骤(a)中，将四甲基胍加入到7-氮杂吲哚的水悬浮液中，四甲基胍与7-氮杂吲哚的摩尔比为15:10，7-氮杂吲哚与水的摩尔体积比为10:50mmol/mL，然后在30℃条件下搅拌10min后，加入醛类化合物并在30℃下搅拌反应18h，醛类化合物与7-氮杂吲哚的摩尔比为10:10，然后过滤，滤饼用乙酸乙酯/石油醚重结晶得醇(A)。

4.  如权利要求2所述的3-烷基取代-7-氮杂吲哚化合物的合成方法，其特征在于：步骤(a)中，所述的醛类化合物为苯甲醛、4-甲氧基苯甲醛、3-甲氧基苯甲醛、2-甲氧基苯甲醛、4-氯苯甲醛、3-氯苯甲醛、2-氯苯甲醛、4-氟苯甲醛、3-氟苯甲醛、3-三氟甲基苯甲醛或吡啶-2-甲醛中的一种。

5.  如权利要求2所述的3-烷基取代-7-氮杂吲哚化合物的合成方法，其特征在于：步骤(a)中，将醇(A)加入到乙酸乙酯中，醇(A)与乙酸乙酯的摩尔体积比为10:100mmol/mL，醇(A)溶解后加入对甲苯亚磺酸和对甲苯磺酸，对甲苯亚磺酸与醇(A)的摩尔比为12:10，对甲苯磺酸与醇(A)的摩尔比为15:10，然后在30℃下搅拌反应24h后，过滤，滤饼用乙酸乙酯/石油醚重结晶得3-(1-芳砜烷基)-7-氮杂吲哚(1)。

6.  如权利要求2所述的3-烷基取代-7-氮杂吲哚化合物的合成方法，其特征在于：步骤(b)中，碳酸钾或氢氧化钠与3-(1-芳砜烷基)-7-氮杂吲哚(1)的摩尔比为12:10，亲核试剂与3-(1-芳砜烷基)-7-氮杂吲哚(1)的摩尔比为12:10。

7.  如权利要求2所述的3-烷基取代-7-氮杂吲哚化合物的合成方法，其特征在于：步骤(b)中，所述的亲核试剂为碳亲核试剂、氮亲核试剂、氧亲核试剂或硫亲核试剂中的一种。

8.  如权利要求7所述的3-烷基取代-7-氮杂吲哚化合物的合成方法，其特征在于：所述的碳亲核试剂为蒽酮、乙酰丙酮、1,3-二苯基-1,3-丙二酮或丙二腈中的一种；所述的氮亲核试剂为苯胺、4-甲氧基苯胺、3-甲氧基苯胺、2-甲氧基苯胺、4-甲基苯胺、4-氯苯胺、3-氯苯胺或正丁胺中的一种；所述的氧亲核试剂为甲醇或乙醇；所述的硫亲核试剂为对甲苯硫酚。

9.  如权利要求2所述的3-烷基取代-7-氮杂吲哚化合物的合成方法，其特征在于：步骤(a)中，所述的乙酸乙酯/石油醚混合物中乙酸乙酯与石油醚的体积比为1：4-6。

10.  如权利要求2所述的3-烷基取代-7-氮杂吲哚化合物的合成方法，其特征在于：步骤(b)中，所述的乙酸乙酯/石油醚混合物中乙酸乙酯与石油醚的体积比为1：2-5。

说明书

一种3-烷基取代-7-氮杂吲哚化合物的合成方法
技术领域
本发明涉及有机合成技术领域，尤其涉及一种3-烷基取代-7-氮杂吲哚化合物的合成方法。
背景技术
尽管3-烷基取代-7-氮杂吲哚化合物已经被发现广泛地存在于大量天然产物和药物活性的化合物中，然而仅有一篇文献(M.Alfonsi,A.Arcadi,G.Bianchi,F.Marinelli,A.Nardini,Eur.J.Org.Chem.2006,2393-2402)报道了以金作催化剂，在100℃或140℃条件下以7-氮杂吲哚(作亲核试剂)进攻α,β-不饱和酮(作亲电试剂)去合成含碳3-烷基取代-7-氮杂吲哚化合物。然而，这种策略存在着以下的不足：(1)由于7-氮杂吲哚3位弱的亲核性，反应常常需要比较苛刻的条件，比如贵金属或过渡金属催化剂以及高的反应温度；(2)由于缺乏相应的亲电试剂，很多3-烷基取代-7-氮杂吲哚化合物均不能通过这种方法来合成。
考虑到亲核试剂的种类非常多，比如：碳亲核试剂、氮亲核试剂、氧亲核试剂以及硫亲核试剂等，因此我们把亲电试剂构造成含有7-氮杂吲哚片段的结构，然后让各种各样的亲核试剂能够和这类亲电试剂作用，必将能够合成出各种各样结构多变的3-烷基取代-7-氮杂吲哚化合物。
发明内容
本发明目的在于提供一种简单、高效且具有广泛普适性的合成各种各样的3-烷基取代-7-氮杂吲哚化合物的方法。
本发明采取的技术方案是：
本发明的3-烷基取代-7-氮杂吲哚化合物的合成方法的合成路线如下：

本发明的3-烷基取代-7-氮杂吲哚化合物的合成方法的具体步骤如下：
(a)3-(1-芳砜烷基)-7-氮杂吲哚(1)的合成：
将四甲基胍加入到7-氮杂吲哚的水悬浮液中，四甲基胍与7-氮杂吲哚的摩尔比为10-20:10，7-氮杂吲哚与水的摩尔体积比为10:30-70mmol/mL，然后在20-40℃条件下搅拌5-15min后，加入醛类化合物并在20-40℃下搅拌反应12-24h，醛类化合物与7-氮杂吲哚的摩尔比为5-15:10，然后过滤，滤饼用乙酸乙酯/石油醚重结晶得醇(A)；
将醇(A)加入到乙酸乙酯中，醇(A)与乙酸乙酯的摩尔体积比为10:80-120mmol/mL，醇(A)溶解后加入对甲苯亚磺酸和对甲苯磺酸，对甲苯亚磺酸与醇(A)的摩尔比为10-15:10，对甲苯磺酸与醇(A)的摩尔比为10-20:10，然后在20-40℃下搅拌反应18-30h后，过滤，滤饼用乙酸乙酯/石油醚重结晶得3-(1-芳砜烷基)-7-氮杂吲哚(1)；
(b)3-烷基取代-7-氮杂吲哚化合物的合成：
往3-(1-芳砜烷基)-7-氮杂吲哚(1)中加入碳酸钾或氢氧化钠，然后再加入亲核试剂，碳酸钾或氢氧化钠与3-(1-芳砜烷基)-7-氮杂吲哚(1)的摩尔比为10-15:10，亲核试剂与3-(1-芳砜烷基)-7-氮杂吲哚(1)的摩尔比为10-15:10，然后在40-65℃下搅拌反应1-36h，然后使用乙酸乙酯/石油醚进行柱层析的到3-烷基取代-7-氮杂吲哚化合物。
步骤(a)中，优先将四甲基胍加入到7-氮杂吲哚的水悬浮液中，四甲基胍与7-氮杂吲哚的摩尔比为15:10，7-氮杂吲哚与水的摩尔体积比为10:50mmol/mL，然后在30℃条件下搅拌10min后，加入醛类化合物并在30℃下搅拌反应18h，醛类化合物与7-氮杂吲哚的摩尔比为10:10，然后过滤，滤饼用乙酸乙酯/石油醚重结晶得醇(A)。
步骤(a)中，所述的醛类化合物是苯甲醛、4-甲氧基苯甲醛、3-甲氧基苯甲醛、2-甲氧基苯甲醛、4-氯苯甲醛、3-氯苯甲醛、2-氯苯甲醛、4-氟苯甲醛、3-氟苯甲醛、3-三氟甲基苯甲醛或吡啶-2-甲醛。
步骤(a)中，优先将醇(A)加入到乙酸乙酯中，醇(A)与乙酸乙酯的摩尔体积比为10:100mmol/mL，醇(A)溶解后加入对甲苯亚磺酸和对甲苯磺酸，对甲苯亚磺酸与醇A的摩尔比为12:10，对甲苯磺酸与醇(A)的摩尔比为15:10，然后在30℃下搅拌反应24h后，过滤，滤饼用乙酸乙酯/石油醚重结晶得3-(1-芳砜烷基)-7-氮杂吲哚(1)。
步骤(b)中，碳酸钾或氢氧化钠与3-(1-芳砜烷基)-7-氮杂吲哚(1)的摩尔比为12:10，亲核试剂与3-(1-芳砜烷基)-7-氮杂吲哚(1)的摩尔比为12:10。
步骤(b)中，所述的亲核试剂为碳亲核试剂、氮亲核试剂、氧亲核试剂或硫亲核试剂中的一种。所述的碳亲核试剂为蒽酮、乙酰丙酮、1,3-二苯基-1,3-丙二酮或丙二腈，所述的氮亲核试剂为苯胺、4-甲氧基苯胺、3-甲氧基苯胺、2-甲氧基苯胺、4-甲基苯胺、4-氯苯胺、3-氯苯胺或正丁胺，所述的氧亲核试剂为甲醇或乙醇，所述的硫亲核试剂为对甲苯硫酚。
步骤(a)中，所述的乙酸乙酯/石油醚混合物中乙酸乙酯与石油醚的体积比为1：4-6。
步骤(b)中，所述的乙酸乙酯/石油醚混合物中乙酸乙酯与石油醚的体积比为1：2-5。
本发明的积极效果如下：
本发明在简单的反应条件下，方便高效地合成了各种结构的3-烷基取代-7-氮杂吲哚化合物。
具体实施方式
下面的实施例是对本发明的进一步详细描述。
实施例1
一、3-(1-芳砜烷基)-7-氮杂吲哚1的合成
将四甲基胍(15mmol)加入到7-氮杂吲哚(10mmol)的水(50mL)悬浮液中。在30℃条件下搅拌10分钟后，加入相应的醛(10mmol)并在30℃下搅拌反应18h。过滤，滤饼用乙酸乙酯/石油醚重结晶得醇A。将A(10mmol)加入到乙酸乙酯(100mL)中，溶解后加入对甲苯亚磺酸(12mmol)和对甲苯磺酸(15mmol)，在30℃下搅拌反应24h后，过滤，滤饼用乙酸乙酯/石油醚重结晶得3-(1-芳砜烷基)-7-氮杂吲哚1，产物经氢核磁共振谱(¹H NMR)、碳核磁共振谱(¹³C NMR)及高分辨质谱(HRMS)所确证。
(dd,J＝7.9,4.7Hz,1H),5.63(s,1H),2.35(s,3H)；¹³C NMR(100MHz,CDCl₃)δ147.7,144.5,142.7,135.0,133.0,130.1,129.3,129.0,128.8,128.6,128.5,126.1,120.1,116.2,106.5,69.2,21.6；HRMS(ESI)Calcd for C₂₁H₁₉N₂O₂S[M+H]⁺:363.1167,found:363.1162.
6.20(s,1H),5.74(s,1H),3.70(s,3H),2.27(s,3H)；¹³C NMR(100MHz,DMSO)δ156.9,148.3,144.5,143.7,135.9,130.4,130.3,129.6,128.9,127.2,126.9,122.2,120.9,119.7,116.2,111.6,105.5,59.0,56.1,21.4；HRMS(ESI)Calcd for C₂₂H₂₁N₂O₂S[M+H]⁺:393.1273,found:393.1278.
1H),6.23(s,1H),3.68(s,3H),2.28(s,3H)；¹³C NMR(100MHz,DMSO)δ159.4,148.3,144.4,143.6,136.0,135.7,129.8,129.7,128.9,127.9,126.7,122.7,119.6,116.5,116.0,114.0,106.0,66.9,55.5,21.4；HRMS(ESI)Calcd for C₂₂H₂₁N₂O₂S[M+H]⁺:393.1273,found:393.1255.
8.0Hz,1H),6.35(s,1H),3.51(s,3H),2.30(s,3H)；¹³C NMR(101MHz,DMSO)δ156.9,148.3,144.5,143.7,135.9,130.4,130.3,129.6,128.9,127.2,126.9,122.2,120.9,119.7,116.2,111.6,105.5,59.0,56.1,21.4；HRMS(ESI)Calcd for C₂₂H₂₁N₂O₂S[M+H]⁺:393.1273,found:393.1256.
8.1Hz,2H),7.02(dd,J＝7.9,4.7Hz,1H),6.34(s,1H),2.28(s,3H)；¹³C NMR(100MHz,DMSO)δ147.0,144.7,142.6,135.62,133.6,133.1,132.4,129.8,129.0,128.9,128.8,127.2,120.2,116.1,106.0,65.9,21.4；HRMS(ESI)Calcd for C₂₁H₁₈ClN₂O₂S[M+H]⁺:397.0778,found:397.0771.
J＝8.1Hz,2H),7.02(dd,J＝7.9,4.7Hz,1H),6.34(s,1H),2.27(s,3H)；¹³C NMR(100MHz,DMSO)δ148.1,144.7,143.7,136.4,135.5,133.3,130.7,130.4,129.8,129.1,128.9,128.8,127.7,126.8,119.5,116.1,105.4,66.0,21.4；HRMS(ESI)Calcd for C₂₁H₁₈ClN₂O₂S[M+H]⁺:397.0778,found:397.0765.
(dd,J＝15.9,7.2Hz,2H),7.26(d,J＝8.0Hz,2H),7.05(dd,J＝7.9,4.7Hz,1H),6.38(s,1H),2.28(s,3H)；¹³C NMR(100MHz,DMSO)δ147.8,144.6,143.4,135.1,133.7,131.4,130.9,130.3,129.6,129.4,128.5,127.6,126.7,126.6,119.0,115.9,104.4,62.6,21.1；HRMS(ESI)Calcd for C₂₁H₁₈ClN₂O₂S[M+H]⁺:397.0778,found:397.0777.
(t,J＝8.8Hz,2H),7.02(dd,J＝7.9,4.7Hz,1H),6.30(s,1H),2.26(s,3H)；¹³C NMR(100MHz,DMSO)δ162.4(d,J＝245.4Hz),148.1,144.6,143.6,135.7,132.7,132.6,130.3(d,J＝3.0Hz),129.7,128.9,127.9,126.7,119.6,116.1,115.7,115.5,105.9,66.0,21.4；HRMS(ESI)Calcd for C₂₁H₁₈FN₂O₂S[M+H]⁺:381.1073,found:381.1089.
7.6Hz,2H),7.14(t,J＝7.6Hz,1H),7.03(dd,J＝6.9,4.7Hz,1H),6.37(s,1H),2.26(s,3H)；¹³C NMR(100MHz,DMSO)δ162.2(d,J＝243.8Hz),148.2,144.6,1437,136.8(d,J＝7.6Hz),135.7,130.7(d,J＝8.3Hz),129.7,128.9,127.7,126.8,126.7(d,J＝2.4Hz),119.6,117.4,117.2,116.,115.8,115.6,105.5,66.2,21.4；HRMS(ESI)Calcd for C₂₁H₁₈FN₂O₂S[M+H]⁺:381.1073,found:381.1063.
1H),7.53(d,J＝8.1Hz,2H),7.24(d,J＝8.1Hz,2H),7.03(dd,J＝7.9,4.7Hz,1H),6.48(s,1H),2.26(s,3H)；¹³C NMR(100MHz,DMSO)δ148.1,144.8,143.8,135.5,135.3,134.3,130.0,129.8,128.9,127.8,127.3(t,J＝4Hz),126.8,125.5(t,J＝4Hz),119.5,116.2,105.2,66.1,21.4；HRMS(ESI)Calcd for C₂₂H₁₇F₃N₂O₂SNa⁺[M+Na]⁺:453.0860,found:453.0871.
(t,J＝8.0Hz,1H),7.21(d,J＝8.0Hz,2H),7.03(dd,J＝7.8,4.7Hz,1H),6.34(s,1H),2.28(s,3H)；¹³C NMR(100MHz,DMSO)δ153.7,149.6,148.2,144.5,143.4,137.2,135.5,129.5,129.2,128.3,128.1,126.0,123.7,120.0,116.0,104.5,69.5,21.4；HRMS(ESI)Calcd for C₂₀H₁₈N₃O₂S[M+H]⁺:364.1120,found:364.1132.
二、3-烷基取代-7-氮杂吲哚化合物3和5的合成
将碳酸钾(0.12mmol)加入到3-(1-芳砜烷基)-7-氮杂吲哚1(0.1mmol)和胺2或对甲苯硫酚4(0.12mmol)的氯仿(1.2mL)溶液中，在65℃下搅拌反应36h。柱层析(乙酸乙酯/石油醚＝1:5-1:3)得到相应的3-烷基取代-7-氮杂吲哚化合物3或5，产物经氢核磁共振谱(¹H NMR)、碳核磁共振谱(¹³C NMR)及高分辨质谱(HRMS)所确证。

2H),7.21-7.14(m,2H),6.97(dd,J＝7.8,4.7Hz,1H),6.62(s,4H),5.95(d,J＝7.1Hz,1H),5.75(d,J＝7.1Hz,1H),3.57(s,3H)；¹³C NMR(100MHz,DMSO)δ151.2,149.2,144.3,143.0,142.8,128.7,127.9,127.6,127.1,123.9,118.6,117.1,115.5,114.8,114.7,55.7,55.4；HRMS(ESI)Calcd for C₂₁H₁₉N₃ONa(M+Na)⁺:352.1426,found:352.1421.
2H),7.29(dd,J＝13.3,6.1Hz,1H),7.09-7.01(m,3H),6.27(dd,J＝13.3,8.2Hz,2H),6.19(s,1H),5.83(d,J＝3.6Hz,1H),4.38(d,J＝3.9Hz,1H),3.71(s,3H)；¹³C NMR(100MHz,CDCl3)δ160.7,149.3,148.8,142.8,142.2,129.9,128.7,128.1,127.4,127.3,124.0,118.9,117.0,115.7,106.5,102.7,99.5,55.9,55.0；HRMS(ESI)Calcd for C₂₁H₁₉N₃ONa(M+Na)⁺:352.1426,found:352.1428.
(m,2H),7.03-6.96(m,1H),6.81(d,J＝7.6Hz,1H),6.65(t,J＝7.4Hz,1H),6.59-6.47(m,2H),5.85(s,1H),4.99(s,1H),3.76(s,3H)；13C NMR(100MHz,DMSO)δ149.2,147.0,143.6,143.2,137.4,128.9,127.5,127.4,127.3,124.1,121.3,118.3,116.9,116.6,115.8,111.3,110.2,55.9,55.0；HRMS(ESI)Calcd for C21H20N3O(M+H)+:330.1608,found:330.1618.
＝7.0Hz,1H),7.05(dd,J＝8.2,5.4Hz,2H),6.97(d,J＝8.0Hz,2H),6.56(d,J＝8.1Hz,2H),5.80(s,1H),3.83(s,1H),2.24(s,3H)；13C NMR(100MHz,CDCl3)δ149.2,145.2,142.6,142.5,129.7,128.7,128.3,127.4,127.3,126.8,124.0,119.1,117.3,115.7,113.5,56.2,20.4；HRMS(ESI)m/zcalcd for C21H19N3Na(M+Na)+:336.1477,found:336.1500.
1H),7.15(t,J＝7.8Hz,2H),7.06(dd,J＝7.3,4.8Hz,2H),6.72(t,J＝7.3Hz,1H),6.62(d,J＝7.9Hz,2H),5.83(s,1H)；¹³C NMR(100MHz,CDCl3)δ148.8,147.4,142.4,142.1,129.2,128.7,128.5,127.5,127.3,124.1,119.2,117.7,117.3,115.8,113.4,55.9；HRMS(ESI)Calcd for C₂₀H₁₈N₃(M+H)⁺:300.1501,found:300.1521.
7.34-7.29(m,1H),7.11-7.01(m,4H),6.53(d,J＝8.6Hz,2H),5.78(s,1H),4.35(s,1H)；¹³C NMR(100MHz,CDCl3)δ149.0,145.9,142.8,141.7,129.0,128.8,128.2,127.6,127.2,124.0,122.3,118.9,116.8,115.9,114.5,56.0；HRMS(ESI)Calcd for C₂₀H₁₆ClN₃Na(M+Na)⁺:356.0930,found:356.0917.
(t,J＝7.2Hz,1H),7.09-6.97(m,3H),6.67(d,J＝7.9Hz,1H),6.60(s,1H),6.48(d,J＝8.1Hz,1H),5.80(d,J＝4.7Hz,1H),4.40(d,J＝4.4Hz,1H)；¹³C NMR(100MHz,CDCl3)δ149.1,148.4,143.3,141.5,134.9,130.2,128.8,128.0,127.6,127.2,123.7,118.6,117.6,116.8,116.0,113.1,111.5,55.8；HRMS(ESI)Calcd for C₂₀H₁₇ClN₃(M+H)⁺:334.1111,found:334.1109.
7.41(t,J＝7.2Hz,2H),7.34(d,J＝7.0Hz,1H),7.06(dd,J＝7.5,4.7Hz,1H),5.84(d,J＝5.5Hz,1H),2.80(d,J＝7.2Hz,2H),1.77-1.64(m,2H),1.22(dt,J＝14.4,7.2Hz,2H),0.80(t,J＝7.3Hz,3H)；¹³C NMR(100MHz,DMSO)δ148.4,143.8,137.4,129.3,129.0,128.4,127.5,125.5,118.2,116.2,109.9,58.0,46.1,27.6,19.9,13.9；HRMS(ESI)Calcd for C₁₈H₂₁N₃Na(M+Na)⁺:302.1633,found:302.1637.
(d,J＝8.5Hz,2H),6.57(d,J＝8.5Hz,2H),5.69(s,1H),4.04(s,1H), 3.81(s,3H),3.73(s,3H)；¹³C NMR(100MHz,CDCl3)δ158.8,152.1,149.3,142.9,141.9,134.7,128.4,128.1,123.6,118.8,117.7,115.7,114.8,114.6,114.0,56.2,55.8,55.3；HRMS(ESI)Calcd for C₂₂H₂₁N₃O₂Na(M+Na)⁺:382.1531,found:382.1524.
1H),7.06(dt,J＝8.0,6.9Hz,4H),6.83(dd,J＝8.1,2.1Hz,1H),6.75(d,J＝8.9Hz,2H),6.58(d,J＝8.9Hz,2H),5.71(s,1H),4.09(s,1H),3.78(s,3H),3.73(s,3H)；¹³C NMR(100MHz,CDCl3)δ159.9,152.2,149.3,144.4,142.8,141.8,129.7,128.2,123.8,119.7,118.9,117.2,115.7,114.8,114.6,113.0,112.5,56.8,55.8,55.2；HRMS(ESI)Calcd for C₂₂H₂₁N₃O₂Na(M+Na)⁺:382.1531,found:382.1531.
(d,J＝9.2Hz,2H),6.98-6.90(m,2H),6.73(d,J＝8.8Hz,2H),6.58(d,J＝8.8Hz,2H),6.14(s,1H),5.30(s,1H),3.82(s,3H),3.72(s,3H)；¹³C NMR(100MHz,CDCl3)δ156.9,152.1,148.9,142.3,141.9,130.4,128.6,128.4,127.9,123.6,120.8,119.5,117.1,115.6,114.8,114.6110.8, 55.8,55.6,50.4；HRMS(ESI)Calcd for C₂₂H₂₁N₃O₂Na(M+Na)⁺:382.1531,found:382.1525.
J＝8.4Hz,2H),7.06(dd,J＝7.9,4.8Hz,1H),7.01(d,J＝1.1Hz,1H),6.75(d,J＝8.9Hz,2H),6.55(d,J＝8.9Hz,2H),5.71(d,J＝2.1Hz,1H),4.06(d,J＝2.8Hz,1H),3.73(s,3H)；¹³C NMR(100MHz,CDCl3)δ152.3,149.3,143.0,141.5,141.1,133.0,128.8,128.6,128.1,123.8,118.7,117.0,115.8,114.9,114.6,56.2,55.8；HRMS(ESI)m/zcalcd for C₂₁H₁₉ClN₃O(M+H)⁺:364.1217,found:364.1197.
(dd,J＝12.9,5.7Hz,2H),7.10-7.01(m,2H),6.76(d,J＝8.8Hz,2H),6.56(d,J＝8.8Hz,2H),5.70(s,1H),4.07(s,1H),3.73(s,3H)；¹³C NMR(100MHz,CDCl3)δ152.4,149.1,144.8,143.2,141.4,134.6,129.9,128.0,127.6,127.4,125.4,123.7,118.6,116.9,115.9,114.9,114.6,56.4,55.8；HRMS(ESI)Calcd for C₂₁H₁₈ClN₃ONa(M+Na)⁺:386.1038,found:386.1011.
7.32-7.23(m,2H),7.07(dd,J＝7.8,4.8Hz,1H),6.96(s,1H),6.75(d,J＝8.8Hz,2H),6.53(d,J＝8.8Hz,2H),6.14(s,1H),4.14(s,1H),3.73(s,3H)；¹³C NMR(100MHz,CDCl3)δ152.3,149.1,143.1,141.3,139.5,133.5,129.9,128.6,128.4,128.1,127.2,123.9118.9,115.9,115.7,114.9,114.4,55.7,53.3；HRMS(ESI)Calcd for C₂₁H₁₈ClN₃ONa(M+Na)⁺:386.1038,found:386.1016.
4H),6.75(d,J＝8.9Hz,2H),6.56(d,J＝8.8Hz,2H),5.72(s,1H),3.73(s,3H)；¹³C NMR(100MHz,CDCl3)δ163.3,160.8,152.3,149.2,142.9,141.6,138.2(d,J＝3.0Hz),128.8(d,J＝8.0Hz),128.1,123.7,118.8,117.3,115.8,115.6,115.4,114.8,114.6,56.1,55.8；HRMS(ESI)Calcd for C₂₁H₁₉FN₃O(M+H)⁺:348.1512,found:348.1525.
7.12-7.02(m,2H),6.98(s,1H),6.75(d,J＝8.8Hz,2H),6.56(d,J＝8.8Hz,2H),5.73(s,1H),4.08(s,1H),3.73(s,3H)；¹³C NMR(100MHz,CDCl3)δ164.4,162.0,152.3,149.2,145.4(d,J＝6.0Hz),143.1,141.5,130.1(d,J＝8.0Hz),128.1,123.7,122.9(d,J＝3.0Hz),118.7,116.9,115.9,114.9,114.6,114.3(d,J＝12.0Hz),114.1(d,J＝12.0Hz),56.4(d,J＝2.0Hz),55.8；HRMS(ESI)Calcd for C₂₁H₁₉FN₃O(M+H)⁺:348.1512,found:348.1513.
(d,J＝7.7Hz,1H),7.48(t,J＝7.7Hz,1H),7.07(dd,J＝7.9,4.8Hz,1H),6.99(s,1H),6.76(d,J＝8.8Hz,2H),6.55(d,J＝8.8Hz,2H),5.79(s,1H),4.09(s,1H),3.73(s,3H)；¹³C NMR(100MHz,CDCl3)δ152.5,149.2,143.7,143.2,141.4,130.6,129.1,128.0,124.3(q,J＝4.0),124.1(q,J＝4.0Hz)123.8,118.6,116.8,115.9,114.9,114.6,56.6,55.7；HRMS(ESI)Calcd for C₂₂H₁₉F₃N₃O(M+H)⁺:398.1480,found:398.1481.
(d,J＝7.8Hz,1H),7.18(s,2H),7.04(dd,J＝7.9,4.8Hz,1H),6.73(d,J＝8.9Hz,2H),6.64(d,J＝8.9Hz,2H),5.84(s,1H),3.71(s,3H)；¹³C NMR(100MHz,CDCl3)δ161.6,152.3,149.3,149.2,142.9,141.6,136.9,128.2,123.5,122.2,121.6,118.8,116.3,115.8,115.0,114.8,58.0,55.7；HRMS(ESI)Calcd for C₂₀H₁₉N₄O(M+H)⁺:331.1559,found:331.1534.
7.19(d,J＝8.0Hz,2H),7.05(dd,J＝7.9,4.8Hz,1H),7.01(d,J＝7.9Hz,2H),5.70(s,1H),2.28(s,3H)；¹³C NMR(100MHz,CDCl3)δ149.2,142.7,141.1,137.0,132.3,131.7,129.5,128.7,128.5,128.4,127.3,124.5,119.3,115.6,114.8,50.9,21.1；HRMS(ESI)Calcd for C₂₁H₁₉N₂S(M+H)⁺:331.1269,found:331.1290.
6.85(d,J＝8.6Hz,2H),5.68(s,1H),3.80(s,3H),2.28(s,3H)；¹³C NMR(100MHz,CDCl3)δ158.7,149.4,142.7,136.8,133.3,132.5,131.5,129.5,128.7,124.5,119.3,115.5,115.1,113.8,55.3,50.2,21.1；HRMS(ESI)Calcd for C₂₂H₂₁N₂₀S(M+H)⁺:361.1375,found:361.1398.
J＝8.1,2.1Hz,1H),5.68(s,1H),3.76(s,3H),2.28(s,3H)；¹³C NMR(100MHz,CDCl3)δ159.7,149.3,142.8,142.6,137.0,132.4,131.6,129.6,129.4,128.7,124.6,120.9,119.4,115.5,114.6,114.1,112.8,55.2,50.8,21.1；HRMS(ESI)Calcd for C₂₂H₂₁N₂₀S(M+H)⁺:361.1375,found:361.1373.
3H),7.07-7.02(m,1H),7.00(d,J＝8.0Hz,2H),6.96-6.86(m,2H),6.29(s,1H),3.82(s,3H),2.27(s,3H)；¹³C NMR(100MHz,CDCl3)δ156.4,149.1,142.9,136.3,133.1,130.7,129.5,129.4,128.4,128.3,124.2,120.8,119.4,115.6,115.2,110.8,55.7,42.2,21.0；HRMS(ESI)Calcd for C₂₂H₂₁N₂₀S(M+H)⁺:361.1375,found:361.1397.
7.18(d,J＝8.0Hz,2H),7.07(dd,J＝7.9,4.8Hz,1H),7.02(d,J＝7.9Hz,2H),5.65(s,1H),2.29(s,3H)；¹³C NMR(100MHz,CDCl3)δ149.2,142.8,139.8,137.3,133.0,132.0,131.7,129.8,129.7,128.7,128.6,124.6,119.2,115.6,114.2,50.3,21.1；HRMS(ESI)Calcd for C₂₁H₁₈ClN₂S(M+H)⁺:365.0879,found:365,0900.
7.08(dd,J＝7.9,4.8Hz,1H),7.02(d,J＝7.9Hz,2H),5.64(s,1H),2.29(s,3H)；¹³C NMR(100MHz,CDCl3)δ149.2,143.3,142.9,137.4,134.3,132.0,131.6,129.7,128.6,128.5,127.5,126.6,124.5,119.2,115.7,114.1,50.521.1；HRMS(ESI)Calcd for C₂₁H₁₈ClN₂S(M+H)⁺:365.0879 found:365.0879.
1H),7.28-7.16(m,5H),7.10-6.99(m,3H),6.27(s,1H),2.28(s,3H)；¹³C NMR(100MHz,CDCl3)δ149.3,142.8,138.6,137.0,133.4,132.1,131.1,130.2,129.6,128.5,128.4,127.1,124.8,119.3,115.7,113.9,46.4,21.1；HRMS(ESI)Calcd for C₂₁H₁₈ClN₂S(M+H)⁺:365.0879,found:365.0893.
J＝7.9,4.8Hz,1H),7.04-6.96(m,4H),5.68(s,1H),2.29(s,3H)；¹³C NMR(100MHz,CDCl3)δ163.1,160.7,149.3,142.6,137.2,137.0(d,J＝3.0Hz),131.9,130.0(d,J＝8.0Hz),129.6,128.7,124.6,119.3,115.5(d,J＝19.0Hz),115.2,114.5,50.2,21.1；HRMS(ESI)Calcd for C₂₁H₁₈FN₂S(M+H)⁺:149.1175,found:349.1198.
7.8Hz,2H),6.95(t,J＝8.2Hz,1H),5.68(s,1H),2.29(s,3H)；¹³C NMR(100MHz,CDCl3)δ164.1,161.6,149.3,142.8,137.4,132.0,131.7,129.8(d,J＝8.0),129.6,128.6,124.6,124.1(d,J＝3.0Hz),119.2,115.6(d,J＝17Hz),115.3,114.4,114.1,50.5,21.1；HRMS(ESI)Calcd for C₂₁H₁₈FN₂S(M+H)⁺:149.1175,found:349.1194.
1H),7.41(t,J＝7.7Hz,1H),7.28(s,1H),7.18(d,J＝8.0Hz,2H),7.09(dd,J＝7.9,4.8Hz,1H),7.02(d,J＝7.9Hz,2H),5.72(s,1H),2.29(s,3H)；¹³C NMR(100MHz,CDCl3)δ149.3,142.8,142.4,137.7,132.5,131.7,131.2,129.7,128.9,128.6,125.2(q,J＝4.0Hz),124.7,124.1(q,J＝4.0Hz),119.2,115.7,113.8,50.8,21.1；HRMS(ESI)Calcd for C₂₂H₁₈F₃N₂S(M+H)⁺:399.1143,found:399.1155.
7.45(d,J＝7.8Hz,1H),7.31(s,1H),7.22-7.12(m,3H),7.05(dd,J＝7.9,4.8Hz,1H),6.99(d,J＝7.9Hz,2H),5.82(s,1H),2.27(s,3H)；¹³C NMR(100MHz,CDCl3)δ160.6,149.2,149.1,142.8,137.2,136.7,132.1,131.7,129.6,128.6,124.4,122.7,122.2,119.2,115.6,113.5,52.6,21.1；HRMS(ESI)Calcd for C₂₀H₁₈N₃S(M+H)⁺:332.1221,found:332.1194.
三、3-烷基取代-7-氮杂吲哚化合物7的合成
将碳酸钾(0.12mmol)加入到3-(1-芳砜烷基)-7-氮杂吲哚1(0.1mmol)和醇6(1.2mL)的溶液中，在65℃下搅拌反应36h。柱层析(乙酸乙酯/石油醚＝1:5-1:3)得到相应的3-烷基取代-7-氮杂吲哚化合物7，产物经氢核磁共振谱(¹H NMR)、碳核磁共振谱(¹³C NMR)及高分辨质谱(HRMS)所确证。

5.2Hz,2H),5.69(s,1H),3.77-3.47(m,2H),1.31(t,J＝7.0Hz,3H)；¹³C NMR(100MHz,CDCl3)δ149.4,142.6,141.8,128.7,128.3,127.5,127.1,123.8,119.2,116.5,115.7,76.7,64.3,15.5；HRMS(ESI)Calcd for C₁₆H₁₇N₂O(M+H)⁺:253.1341,found:253.1345.
3.82(s,3H),3.57(dd,J＝7.0,2.6Hz,2H),1.29(t,J＝7.0Hz,3H)；¹³C NMR(100MHz,CDCl3)δ159.1,149.3,142.9,133.8,128.7,128.4,123.4,119.0,117.0,115.8,113.7,76.7,64.1,55.3,15.4；HRMS(ESI)Calcd for C₁₇H₁₉N₂O₂(M+H)⁺:283.1447,found:283.1437.
3H),3.60(q,J＝6.9Hz,2H),1.30(t,J＝7.0Hz,3H)；¹³C NMR(100MHz,CDCl3)δ159.7,149.3,143.4,142.7,129.3,128.7,123.7,119.6, 119.1,116.5,115.8,113.0,112.6,76.7,64.3,55.2,15.5；HRMS(ESI)Calcd for C₁₇H₁₉N₂O₂(M+H)⁺:283.1447,found:283.1493.
1H),3.80(s,3H),3.66-3.55(m,2H),1.29(t,J＝7.0Hz,3H)；¹³C NMR(100MHz,CDCl3)δ156.9,149.1,142.7,130.1,128.5,128.4,127.3,123.3,120.7,119.3,116.5,115.7,110.5,71.1,64.3,55.5,15.5；HRMS(ESI)Calcd for C₁₇H₁₉N₂O₂(M+H)⁺:283.1447,found:283.1445.
1H),3.67-3.47(m,2H),1.29(t,J＝7.0Hz,3H)；¹³C NMR(100MHz,CDCl3)δ149.2,143.0,140.3,133.2,128.6,128.5,128.4,123.6,118.8,116.2,115.9,76.7,64.3,15.4；HRMS(ESI)Calcd for C₁₆H₁₆ClN₂O(M+H)⁺:287.0951,found:287.0977.
1H),3.79-3.43(m,2H),1.30(t,J＝7.0Hz,3H)；¹³C NMR(100MHz,CDCl3)δ149.3,144.1,142.9,134.3,129.6,128.6,127.6,127.1,125.2,123.8,118.9,115.9,76.7,64.4,15.4；HRMS(ESI)Calcd for C₁₆H₁₆ClN₂O(M+H)⁺:287.0951,found:287.0938.
7.8,4.7Hz,2H),6.12(s,1H),3.77-3.49(m,2H),1.31(t,J＝7.0Hz,3H)；¹³C NMR(100MHz,CDCl3)δ149.2,142.7,139.3,133.2,129.5,128.6,128.5,128.3,127.1,124.0,119.2,115.8,114.9,74.2,64.6,15.5；HRMS(ESI)Calcd for C₁₆H₁₆ClN₂O(M+H)⁺:287.0951,found:287.0949.
2H),1.29(t,J＝7.0Hz,3H)；¹³CNMR(100MHz,CDCl3)δ163.4,161.0,149.4,142.8,137.6(d,J＝3.0Hz),128.7(d,J＝8.0Hz),123.7,119.0,116.3,115.8,115.3,115.1,76.7,64.3,15.4；HRMS(ESI)Calcd for C₁₆H₁₆FN₂O(M+H)⁺:271.1247,found:271.1240.
7.94(d,J＝7.8Hz,1H),7.36-7.27(m,1H),7.22(dd,J＝7.9,4.4Hz,2H),7.10(s,1H),7.06(dd,J＝7.8,4.8Hz,1H),6.99(dd,J＝11.6,4.8Hz,1H),5.66(s,1H),3.59(d,J＝8.8,1.8Hz,2H),1.30(t,J＝7.0Hz,3H)；¹³C NMR(100MHz,CDCl3)δ164.2,161.8,149.3,144.6(d,J＝7.0Hz),142.9,129.8(d,J＝8.0Hz),128.6,123.7,122.6(d,J＝3.0Hz),115.9,114.4,114.2,114.0,113.8,76.7,64.4,15.4；HRMS(ESI)Calcd for C₁₆H₁₆FN₂O(M+H)⁺:271.1247,found:271.1250.
7.6Hz,1H),7.11(s,1H),7.07(dd,J＝7.9,4.8Hz,1H),5.72(s,1H),3.59(dd,J＝9.1,7.2,2.0Hz,2H),1.30(t,J＝7.0Hz,3H)；¹³C NMR(100MHz,CDCl3)δ149.4,143.0,142.9,130.3,128.8,128.6,124.3(q,J＝4.0Hz),123.9,123.7(q,J＝4.0Hz),118.9,116.6,115.9,115.7,76.7,64.5,15.4；HRMS(ESI)Calcd for C₁₇H₁₆F₃N₂O(M+H)⁺:321.1215,found:321.1230.
J＝16.0,11.2,4.5Hz,2H),7.19(dd,J＝13.9,7.4Hz, 2H),7.03(dd,J＝7.8,4.8Hz,1H),5.78(s,1H),3.71-3.57(m,2H),1.30(t,J＝7.0Hz,3H)；¹³C NMR(100MHz,CDCl3)δ161.7,149.1,149.0,142.9,136.8,128.6,123.4,122.4,120.8,118.8,115.8,115.3,79.3,64.6,15.4；HRMS(ESI)Calcd for C₁₅H₁₆N₃O(M+H)⁺:254.1293,found:254.1308.
(s,1H),7.04(dd,J＝7.9,4.8Hz,1H),5.55(s,1H),3.43(s,3H)；¹³C NMR(100MHz,CDCl3):δ149.2,143.1,141.2,128.6,128.4,127.6,127.1,123.4,118.8,116.4,115.9,79.7,56.7；HRMS(ESI)Calcd for C₁₅H₁₅N₂O(M+H)⁺:239.1184,found:239.1204.
四、3-烷基取代-7-氮杂吲哚化合物9、11或13的合成
将氢氧化钠(0.12mmol)加入到3-(1-芳砜烷基)-7-氮杂吲哚1(0.1mmol)和碳亲核试剂8、10或12(0.12mmol)的四氢呋喃(1.0mL)溶液中，在40℃下搅拌反应1h(对于1与8或10的反应)或2.5h(对于1与12的反应)后，柱层析(乙酸乙酯/石油醚＝1:5-1:2)得到相应的3-烷基取代-7-氮杂吲哚化合物9、11或13，产物经氢核磁共振谱(¹H NMR)、碳核磁共振谱(¹³C NMR)及高分辨质谱(HRMS)所确证。

1H),7.43(d,J＝5.9Hz,1H),7.39(d,J＝7.2Hz,1H),7.32(dd,J＝11.3,7.5Hz,3H),7.20(d,J＝7.4Hz,1H),7.14(d,J＝3.8Hz,3H),6.95(d,J＝3.9Hz,2H),6.88(dd,J＝7.8,4.7Hz,1H),6.59(d,J＝1.4Hz,1H),5.20(d,J＝4.8Hz,1H),4.90(d,J＝4.8Hz,1H)；¹³C NMR(100MHz,DMSO)δ183.8,148.4,143.5,143.1,143.0,140.5,133.3,133.1,132.3,132.2,129.6,129.6,129.4,128.2,127.7,127.5,127.0,127.0,126.3,126.1,125.2,119.7,115.4,111.5,54.1,49.1；HRMS(ESI)Calcd for C₂₈H₂₁N₂O[M+H]⁺:401.1654,found:401.1654.
1H),7.70(d,J＝7.4Hz,1H),7.49–7.39(m,3H),7.33(d,J＝7.5Hz,1H),7.28(d,J＝7.8Hz,1H),7.23(d,J＝7.5Hz,1H),6.95(dd,J＝7.5,4.9Hz,1H),6.83(d,J＝8.4Hz,2H),6.68(d,J＝8.5Hz,2H),6.58(s,1H),5.15(d,J＝4.6Hz,1H),4.87(d,J＝4.6Hz,1H),3.66(s,3H)；¹³C NMR(100MHz,DMSO)δ183.7,158.2,148.5,143.5,143.2,143.0,135.0,133.3,133.1,132.3,130.6,129.6,129.4,127.6,127.4,127.2,127.1,126.2,126.1,125.1,119.6,115.4,113.5,112.0,55.4,53.3,49.2；HRMS(ESI)Calcd for C₂₉H₂₂N₂O₂Na⁺[M+Na]⁺:453.1579,found:453.1595.
7.33(t,J＝7.5Hz,1H),7.28(t,J＝8.5Hz,2H),7.03(t,J＝7.8Hz,1H),6.89(dd,J＝7.9,4.7Hz,1H),6.71(dd,J＝8.1,1.8Hz,1H),6.60(d,J＝2.1Hz,1H),6.50(d,J＝8.7Hz,2H),5.20(d,J＝4.9Hz,1H),4.87(d,J＝4.9Hz,1H),3.57(s,3H)；¹³C NMR(100MHz,DMSO)δ183.8,159.1,148.45,143.4,143.2,143.0,142.1,133.3,133.2,132.3,132.3,129.6,129.4,129.2,127.7,127.5,127.1,126.3,126.1,125.1,121.9,119.7, 115.4,115.1,112.7,111.6,55.3,54.0,48.9；HRMS(ESI)Calcd for C₂₉H₂₃N₂O₂[M+H]⁺:431.1760,found:431.1756.
1H),7.51(d,J＝13.1Hz,2H),7.46–7.38(m,2H),7.31(t,J＝6.2Hz,2H),7.21(dd,J＝10.2,6.2Hz,1H),6.99(d,J＝8.1Hz,1H),6.85(d,J＝7.3Hz,1H),6.79(dd,J＝7.6,4.7Hz,1H),6.72(d,J＝3.8Hz,2H),6.42(s,1H),5.28(d,J＝4.3Hz,1H),5.12(d,J＝4.3Hz,1H),3.84(s,3H)；¹³C NMR(100MHz,DMSO)δ184.0,157.1,148.1,144.6,142.9,142.8,133.7,132.8,132.7,131.8,130.1,129.9,129.3,128.9,128.5,127.7,127.3,126.3,126.2,126.0,125.4,120.1,120.0,115.3,111.4,110.4,56.1,47.4,46.3；HRMS(ESI)Calcd for C₂₉H₂₃N₂O₂[M+H]⁺:431.1760,found:431.1746.
Hz,3H),7.33(t,J＝7.4Hz,1H),7.28(d,J＝7.7Hz,1H),7.24(d,J＝7.5Hz,1H),7.18(d,J＝8.2Hz,2H),6.94(d,J＝8.2Hz,2H),6.88(dd,J＝7.7,4.7Hz,1H),6.62(s,1H),5.19(d,J＝4.7Hz,1H),4.90(d,J＝4.6Hz,1H)；¹³C NMR(100MHz,DMSO)δ183.8,148.4,143.2,143.1, 142.9,139.6,133.3,133.1,132.4,131.6,131.4,129.6,129.4,128.1,127.8,127.6,127.1,126.3,126.2,125.2,119.6,115.5,111.3,53.4,48.9；HRMS(ESI)Calcd for C₂₈H₂₀ClN₂O[M+H]⁺:435.1264,found:435.1267.
7.33(t,J＝7.4Hz,2H),7.18(tt,J＝14.9,7.9Hz,3H),7.03(s,1H),6.92(dd,J＝12.6,5.7Hz,2H),6.66(d,J＝12.3Hz,1H),5.21(d,J＝5.0Hz,1H),4.91(d,J＝5.0Hz,1H)；¹³C NMR(100MHz,DMSO)δ183.7,143.3,143.2,142.8,142.5,133.3,133.0,133.0,132.4,132.3,130.0,129.7,129.5,129.4,128.2,127.8,127.7,127.6,127.0,126.4,126.2,125.4,125.2,120.0,115.5,111.3,53.5,48.8；HRMS(ESI)Calcd for C₂₈H₂₀ClN₂O[M+H]⁺:435.1264,found:435.1275.
7.33(t,J＝7.4Hz,1H),7.26(d,J＝7.4Hz,2H),6.96–6.89(m,5H),6.65(s,1H),5.18(d,J＝4.7Hz,1H),4.91(d,J＝4.7Hz,1H)；¹³C NMR(100MHz,DMSO)δ183.8,161.3(d,J＝243.0Hz),148.1,143.2,143.1, 143.0,136.6,133.3,133.1,132.4(d,J＝6.9Hz),131.4(d,J＝7.8Hz),129.6,129.4,127.7,127.6,127.3,126.2(d,J＝10.8Hz),125.2,125.0,119.6,115.4,115.0,114.8,111.7,53.2,49.0；HRMS(ESI)Calcd for C₂₈H₂₀FN₂O[M+H]⁺:419.1560found:419.1542.
7.33(t,J＝7.5Hz,2H),7.17(dd,J＝14.3,7.8Hz,2H),6.99(dd,J＝11.8,4.8Hz,1H),6.87(dd,J＝7.9,4.7Hz,1H),6.81(t,J＝5.6Hz,2H),6.65(d,J＝2.1Hz,1H),5.21(d,J＝5.1Hz,1H),4.91(d,J＝5.1Hz,1H)；¹³C NMR(100MHz,DMSO)δ183.8,162.2(d,J＝243.0Hz),148.4,143.7(d,J＝7.0Hz),143.4,143.1,142.8,133.3,133.1,132.3(d,J＝8.5Hz),130.1(d,J＝8.3Hz),129.6,129.4,127.8,127.6,127.0,126.3,126.2,125.6(d,J＝2.3Hz),125.2,119.6,116.4,116.2,115.4,113.9,113.7,111.1,53.7,48.9；HRMS(ESI)Calcd for C₂₈H₁₉FN₂ONa⁺[M+Na]⁺:441.1379,found:441.1401.
2H),7.42(q,J＝7.8Hz,2H),7.34(dd,J＝12.1,4.8Hz,2H),7.28(d,J＝ 7.6Hz,1H),7.21(dd,J＝12.1,7.9Hz,2H),7.10(s,1H),6.93(dd,J＝7.9,4.7Hz,1H),6.73(d,J＝2.1Hz,1H),5.25(d,J＝5.1Hz,1H),5.01(d,J＝5.1Hz,1H)；¹³C NMR(100MHz,DMSO)δ183.6,148.5,143.3,142.9,142.8,141.6,133.7,133.2,132.4,132.3,129.6,129.4,129.2,129.0,128.7,127.8,127.6,127.3,126.3,126.3,126.1(q,J＝3.6Hz),125.9,125.1,123.8(q,J＝3.7Hz),123.2,119.5,115.5,111.4,53.8,48.7；HRMS(ESI)Calcd for C₂₉H₂₀F₃N₂O[M+H]⁺:469.1528,found:469.1546.
1H),7.47(t,J＝7.3Hz,1H),7.41(d,J＝7.5Hz,1H),7.33(t,J＝7.5Hz,2H),7.29–7.23(m,2H),7.15(d,J＝7.8Hz,1H),6.97(d,J＝7.8Hz,1H),6.87(d,J＝7.6Hz,1H),6.72(dd,J＝7.8,4.7Hz,1H),6.59(d,J＝1.9Hz,1H),5.49(d,J＝5.6Hz,1H),4.82(d,J＝5.6Hz,1H)；¹³C NMR(100MHz,DMSO)δ183.9,160.8,149.2,148.1,144.7,142.9,142.6,136.9,133.6,133.0,132.5,131.9,129.4,129.2,127.6,127.3,126.7,126.3,126.2,126.1,124.0,122.4,119.9,115.2,109.8,56.2,48.5；HRMS(ESI)Calcd for C₂₇H₂₀N₃ONa⁺[M+Na]⁺:424.1426,found:424.1423.
7.2Hz,1H),7.01(dd,J＝7.9,4.7Hz,1H),5.86(d,J＝9.4Hz,1H),5.23(d,J＝9.4Hz,1H)；¹³C NMR(100MHz,DMSO)δ148.8,143.7,139.3,129.2,128.4,127.5,123.9,118.6,115.9,114.4,114.2,111.8,42.8,28.9；HRMS(ESI)Calcd for C₁₇H₁₃N₄[M+H]⁺:273.1140,found:273.1150.
J＝8.4Hz,2H),5.79(d,J＝9.1Hz,1H),5.16(d,J＝9.1Hz,1H),3.72(s,3H)；¹³C NMR(100MHz,DMSO)δ159.3,148.8,143.7,131.1,129.7,127.5,123.7,118.6,115.9,114.5,114.5,114.2,112.1,55.5,42.2,29.2；HRMS(ESI)Calcd for C₁₈H₁₄ON₄Na⁺[M+Na]⁺:325.1065,found:325.1069.
(d,J＝9.5Hz,1H),5.20(d,J＝9.5Hz,1H),3.72(s, 3H)；¹³C NMR(100MHz,DMSO)δ159.9,148.7,143.7,140.8,130.4,127.5,123.9,120.5,118.6,115.9,114.5,114.4,114.2,113.4,111.7,55.5,42.8,28.8；HRMS(ESI)Calcd for C₁₈H₁₄ON₄Na⁺[M+Na]⁺:325.1065,found:325.1063.
6.93(t,J＝7.5Hz,1H),5.87(d,J＝9.9Hz,1H),5.37(d,J＝10.0Hz,1H),3.86(s,3H)；¹³C NMR(100MHz,DMSO)δ157.1,148.6,143.6,129.9129.0,127.2,126.7,124.3,121.1,118.8,116.0,114.6,114.2,112.1,111.2,56.1,37.5,27.8；HRMS(ESI)Calcd for C₁₈H₁₅ON₄[M+H]⁺:303.1246,found:303.1276.
Hz,1H),5.87(d,J＝9.3Hz,1H),5.30(d,J＝9.3Hz,1H)；¹³C NMR(100MHz,DMSO)δ148.8,143.8,138.3,133.1,130.4,129.2,127.4,124.0,118.5,116.0,114.2,114.0,111.3,42.1,28.8；HRMS(ESI)Calcd for C₁₇H₁₂ClN₄[M+H]⁺:307.0750,found:307.0763.
1H),7.37(d,J＝8.1Hz,1H),7.04(dd,J＝7.9,4.7Hz,1H),5.92(d,J＝9.7Hz,1H),5.33(d,J＝9.7Hz,1H)；¹³C NMR(100MHz,DMSO)δ148.7,143.9,141.8,133.8,131.2,128.5,128.3,127.4,127.2,124.1,118.5,116.1,114.2,114.0,111.1,42.2,28.7；HRMS(ESI)Calcd for C₁₇H₁₂ClN₄[M+H]⁺:307.0750,found:307.0757.
1H),7.35(t,J＝7.4Hz,1H),7.05(t,J＝5.65Hz,1H),5.95(d,J＝9.5Hz,1H),5.58(d,J＝9.6Hz,1H)；¹³C NMR(100MHz,DMSO)δ148.6,143.8,136.3,133.5,130.5,130.3,129.1,128.4,127.2,124.9,118.5,116.2,113.9,113.8,110.4,28.2；HRMS(ESI)Calcd for C₁₇H₁₂ClN₄[M+H]⁺:307.0750,found:307.0760.
4.7Hz,1H),5.83(d,J＝9.2Hz,1H),5.28(d,J＝9.3Hz,1H)；¹³C NMR(100MHz,DMSO)δ162.1(d,J＝244.5Hz),148.7,143.8,135.4(d,J＝3.0Hz),130.6(d,J＝8.3Hz),127.5,123.9,118.5,116.2,116.0(d,J＝2.2Hz),114.3,114.0,111.6,42.0,29.0；HRMS(ESI)Calcd for C₁₇H₁₂FN₄[M+H]⁺:291.1046,found:291.1065.
1H),7.03(dt,J＝10.3,5.2Hz,1H),5.89(d,J＝9.6Hz,1H),5.32(d,J＝9.6Hz,1H)；¹³C NMR(100MHz,DMSO)δ162.6(d,J＝244.4Hz),148.7,143.9,142.1(d,J＝7.1Hz),131.4(d,J＝8.3Hz),127.4,124.6(d,J＝2.7Hz),124.1,118.5,116.0,115.4(d,J＝7.1Hz),115.2(d,J＝8.4Hz),114.2,114.0,111.2,42.3,28.7；HRMS(ESI)Calcd for C₁₇H₁₂FN₄[M+H]⁺:291.1046,found:291.1073.
(dd,J＝7.9,4.7Hz,1H),5.97(d,J＝9.5Hz,1H),5.46(d,J＝9.5Hz,1H)；¹³C NMR(100MHz,DMSO)δ148.7,143.9,140.7,132.6,130.5,130.1,129.8,127.4,125.3(q,J＝3.6Hz),125.2(q,J＝3.6 Hz),124.2,118.5,116.1,114.1,113.9,111.0,42.3,28.7；HRMS(ESI)Calcd for C₁₈H₁₁F₃N₄Na⁺[M+Na]⁺:363.0834,found:363.0855.
(t,J＝6.3Hz,1H),6.46(dd,J＝8.8,6.4Hz,1H),6.29(s,2H)；¹³C NMR(100MHz,DMSO)δ149.0,143.4,138.6,128.3,124.3,122.5,121.3,119.3,118.9,117.8,116.1,116.0,111.8,106.2,105.5,78.2；HRMS(ESI)Calcd for C₁₆H₁₂N₅[M+H]⁺:274.1093,found:274.1073.
1H),6.98(dd,J＝7.5,4.7Hz,1H),5.27(d,J＝12.2Hz,1H),4.95(d,J＝12.2Hz,1H),2.08(s,3H),1.99(s,3H)；¹³C NMR(100MHz,DMSO)δ203.2,202.8,148.7,143.1,142.8,128.8,128.4,127.4,126.8,122.8,118.8,115.6,115.5,72.2,42.4,31.0,30.5；HRMS(ESI)Calcd for C₁₉H₁₈O₂N₂Na⁺[M+Na]⁺:329.1266,found:329.1252.
7.7Hz,1H),5.28(d,J＝12.2Hz,1H),4.92(d,J＝12.2Hz,1H),3.68(s,3H),2.07(s,3H),2.02(s,3H)；¹³C NMR(100MHz,DMSO)δ203.1,202.8,159.6,148.7,144.5,143.1,129.8,127.4,122.8,120.6,118.8,115.5,115.5,114.4,111.8,72.0,55.4,42.3,31.0,30.5；HRMS(ESI)Calcd for C₂₀H₂₁O₂N₂[M+H]⁺:337.1552,found:337.1531.
＝6.8,5.6Hz,1H),5.35(d,J＝12.2Hz,1H),4.99(d,J＝12.2Hz,1H),2.08(s,3H),2.05(s,3H)；¹³C NMR(100MHz,DMSO)δ202.9,202.6,145.5,142.9,133.4,130.6,128.3,127.8,127.1,126.8,126.0,123.2,118.9,115.7,115.1,71.9,41.7,31.0,30.6；HRMS(ESI)Calcd for C₁₉H₁₈ClO₂N₂[M+H]⁺:341.1057,found:341.1030.
1H),7.12(t,J＝8.0Hz,1H),6.97(dd,J＝7.6,4.7Hz,1H),5.34(d,J＝11.8Hz,1H),5.14(d,J＝11.8Hz,1H),2.20(s,3H),1.98(s,3H)；¹³C NMR(100MHz,DMSO)δ203.6,202.7,161.7,148.9,148.6,143.1,137.2,127.8,124.3,123.8,122.0,118.6,115.7,113.3,70.9,44.6,31.1,30.5；HRMS(ESI)Calcd for C₁₈H₁₇O₂N₃Na⁺[M+Na]⁺:330.1218,found:330.1230.
4H),7.38(q,J＝7.7Hz,5H),7.09(t,J＝7.5Hz,2H),6.97(dt,J＝13.4,9.8Hz,3H),5.31(d,J＝11.4Hz,1H)^.；¹³C NMR(100MHz,DMSO)δ194.8,194.3,148.4,143.0,142.6,136.6,134.2,129.2,129.1,129.0,128.9,128.5,127.4,126.7,123.1,119.2,116.0,115.6,60.1,44.0.；HRMS(ESI)Calcd for C₂₉H₂₂O₂N₂Na⁺[M+Na]⁺:453.1579,found:453.1574.
(d,J＝7.6Hz,1H),6.99(ddd,J＝13.4,9.9,7.9Hz,3H),6.51(dd,J＝8.0,1.5Hz,1H),5.29(d,J＝11.4Hz,1H),3.62(s,3H)；¹³C NMR(100MHz,DMSO)δ194.7,194.2,159.4,148.5,144.4,143.0,136.7,136.7,134.1,129.4,129.3,129.1,129.1,129.1,127.4,123.2,121.3,119.2,115.9,115.5,114.8,111.9,60.0,55.4,44.0；HRMS(ESI)Calcd for C₃₀H₂₄O₃N₂Na⁺[M+Na]⁺:483.1685,found:483.1674.
Hz,1H),7.06–6.98(m,3H),5.32(d,J＝11.4Hz,1H)；¹³C NMR(100MHz,DMSO)δ194.8,194.1,148.5,145.4,143.2,136.6,134.2,134.1,133.2,130.2,129.2,129.1,129.1,128.8,127.7,127.3,126.6,123.4,119.0,115.6,115.3,59.9,43.6；HRMS(ESI)Calcd for C₂₉H₂₁ClO₂N₂Na⁺[M+Na]⁺:487.1189,found:487.1177.
J＝20.0,8.7Hz,5H),7.24(t,J＝7.6Hz,2H),7.08(dd,J＝11.5,7.1Hz,2H),6.96(dd,J＝7.7,4.7Hz,1H),5.51(d,J＝11.1Hz,1H)；¹³C NMR(100MHz,DMSO)δ195.9,194.7,161.8,148.6,148.5,142.9,137.1,137.1,136.5,133.8,133.8,129.2,128.9,128.9,128.9,127.7,124.7,124.0,122.0,118.9,115.6,113.3,59.2,46.0；HRMS(ESI)Calcd for C₂₈H₂₂O₂N₃[M+H]⁺:432.1712,found:432.1722.
尽管已经示出和描述了本发明的实施例，对于本领域的普通技术人员而言，可以理解在不脱离本发明的原理和精神的情况下可以对这些实施例进行多种变化、修改、替换和变型，本发明的范围由所附权利要求及其等同物限定。

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1、10申请公布号CN104193742A43申请公布日20141210CN104193742A21申请号201410492337922申请日20140923C07D471/0420060171申请人西华师范大学地址637002四川省南充市师大路1号72发明人敬林海秦大斌罗干靳伦强74专利代理机构北京众合诚成知识产权代理有限公司11246代理人裴娜54发明名称一种3烷基取代7氮杂吲哚化合物的合成方法57摘要本发明公开了一种3烷基取代7氮杂吲哚化合物的合成方法，属于有机合成技术领域，本发明首先设计并合成了一系列包含7氮杂吲哚片段的化合物1，其次，以1作为亲电试剂，在温和条件下与各种各样的亲核试剂碳亲。

2、核试剂、氮亲核试剂、氧亲核试剂以及硫亲核试剂反应合成出结构多变的3烷基取代7氮杂吲哚化合物。本发明在简单的反应条件下，方便高效地合成了各种结构的3烷基取代7氮杂吲哚化合物。51INTCL权利要求书2页说明书31页19中华人民共和国国家知识产权局12发明专利申请权利要求书2页说明书31页10申请公布号CN104193742ACN104193742A1/2页21一种3烷基取代7氮杂吲哚化合物的合成方法，其特征在于所述合成方法的合成路线如下2如权利要求1所述的3烷基取代7氮杂吲哚化合物的合成方法，其特征在于所述合成方法的具体步骤如下A31芳砜烷基7氮杂吲哚1的合成将四甲基胍加入到7氮杂吲哚的水悬浮液。

3、中，四甲基胍与7氮杂吲哚的摩尔比为102010，7氮杂吲哚与水的摩尔体积比为103070MMOL/ML，然后在2040条件下搅拌515MIN后，加入醛类化合物并在2040下搅拌反应1224H，醛类化合物与7氮杂吲哚的摩尔比为51510，然后过滤，滤饼用乙酸乙酯/石油醚重结晶得醇A；将醇A加入到乙酸乙酯中，醇A与乙酸乙酯的摩尔体积比为1080120MMOL/ML，醇A溶解后加入对甲苯亚磺酸和对甲苯磺酸，对甲苯亚磺酸与醇A的摩尔比为101510，对甲苯磺酸与醇A的摩尔比为102010，然后在2040下搅拌反应1830H后，过滤，滤饼用乙酸乙酯/石油醚重结晶得31芳砜烷基7氮杂吲哚1；B3烷基取代7。

4、氮杂吲哚化合物的合成往31芳砜烷基7氮杂吲哚1中加入碳酸钾或氢氧化钠，然后再加入亲核试剂，碳酸钾或氢氧化钠与31芳砜烷基7氮杂吲哚1的摩尔比为101510，亲核试剂与31芳砜烷基7氮杂吲哚1的摩尔比为101510，然后在4065下搅拌反应136H，然后使用乙酸乙酯/石油醚进行柱层析得到3烷基取代7氮杂吲哚化合物。3如权利要求2所述的3烷基取代7氮杂吲哚化合物的合成方法，其特征在于步骤A中，将四甲基胍加入到7氮杂吲哚的水悬浮液中，四甲基胍与7氮杂吲哚的摩尔比为1510，7氮杂吲哚与水的摩尔体积比为1050MMOL/ML，然后在30条件下搅拌10MIN后，加入醛类化合物并在30下搅拌反应18H，醛。

5、类化合物与7氮杂吲哚的摩尔比为1010，然后过滤，滤饼用乙酸乙酯/石油醚重结晶得醇A。4如权利要求2所述的3烷基取代7氮杂吲哚化合物的合成方法，其特征在于步骤A中，所述的醛类化合物为苯甲醛、4甲氧基苯甲醛、3甲氧基苯甲醛、2甲氧基苯甲醛、4氯苯甲醛、3氯苯甲醛、2氯苯甲醛、4氟苯甲醛、3氟苯甲醛、3三氟甲基苯甲醛或吡啶2甲醛中的一种。5如权利要求2所述的3烷基取代7氮杂吲哚化合物的合成方法，其特征在于步骤A中，将醇A加入到乙酸乙酯中，醇A与乙酸乙酯的摩尔体积比为10100MMOL/ML，醇A溶解后加入对甲苯亚磺酸和对甲苯磺酸，对甲苯亚磺酸与醇A的摩尔比为1210，权利要求书CN10419374。

6、2A2/2页3对甲苯磺酸与醇A的摩尔比为1510，然后在30下搅拌反应24H后，过滤，滤饼用乙酸乙酯/石油醚重结晶得31芳砜烷基7氮杂吲哚1。6如权利要求2所述的3烷基取代7氮杂吲哚化合物的合成方法，其特征在于步骤B中，碳酸钾或氢氧化钠与31芳砜烷基7氮杂吲哚1的摩尔比为1210，亲核试剂与31芳砜烷基7氮杂吲哚1的摩尔比为1210。7如权利要求2所述的3烷基取代7氮杂吲哚化合物的合成方法，其特征在于步骤B中，所述的亲核试剂为碳亲核试剂、氮亲核试剂、氧亲核试剂或硫亲核试剂中的一种。8如权利要求7所述的3烷基取代7氮杂吲哚化合物的合成方法，其特征在于所述的碳亲核试剂为蒽酮、乙酰丙酮、1,3二苯基。

7、1,3丙二酮或丙二腈中的一种；所述的氮亲核试剂为苯胺、4甲氧基苯胺、3甲氧基苯胺、2甲氧基苯胺、4甲基苯胺、4氯苯胺、3氯苯胺或正丁胺中的一种；所述的氧亲核试剂为甲醇或乙醇；所述的硫亲核试剂为对甲苯硫酚。9如权利要求2所述的3烷基取代7氮杂吲哚化合物的合成方法，其特征在于步骤A中，所述的乙酸乙酯/石油醚混合物中乙酸乙酯与石油醚的体积比为146。10如权利要求2所述的3烷基取代7氮杂吲哚化合物的合成方法，其特征在于步骤B中，所述的乙酸乙酯/石油醚混合物中乙酸乙酯与石油醚的体积比为125。权利要求书CN104193742A1/31页4一种3烷基取代7氮杂吲哚化合物的合成方法技术领域0001本发明涉。

8、及有机合成技术领域，尤其涉及一种3烷基取代7氮杂吲哚化合物的合成方法。背景技术0002尽管3烷基取代7氮杂吲哚化合物已经被发现广泛地存在于大量天然产物和药物活性的化合物中，然而仅有一篇文献MALFONSI,AARCADI,GBIANCHI,FMARINELLI,ANARDINI,EURJORGCHEM2006,23932402报道了以金作催化剂，在100或140条件下以7氮杂吲哚作亲核试剂进攻,不饱和酮作亲电试剂去合成含碳3烷基取代7氮杂吲哚化合物。然而，这种策略存在着以下的不足1由于7氮杂吲哚3位弱的亲核性，反应常常需要比较苛刻的条件，比如贵金属或过渡金属催化剂以及高的反应温度；2由于缺乏相。

9、应的亲电试剂，很多3烷基取代7氮杂吲哚化合物均不能通过这种方法来合成。0003考虑到亲核试剂的种类非常多，比如碳亲核试剂、氮亲核试剂、氧亲核试剂以及硫亲核试剂等，因此我们把亲电试剂构造成含有7氮杂吲哚片段的结构，然后让各种各样的亲核试剂能够和这类亲电试剂作用，必将能够合成出各种各样结构多变的3烷基取代7氮杂吲哚化合物。发明内容0004本发明目的在于提供一种简单、高效且具有广泛普适性的合成各种各样的3烷基取代7氮杂吲哚化合物的方法。0005本发明采取的技术方案是0006本发明的3烷基取代7氮杂吲哚化合物的合成方法的合成路线如下00070008本发明的3烷基取代7氮杂吲哚化合物的合成方法的具体步骤。

10、如下0009A31芳砜烷基7氮杂吲哚1的合成0010将四甲基胍加入到7氮杂吲哚的水悬浮液中，四甲基胍与7氮杂吲哚的摩尔比为102010，7氮杂吲哚与水的摩尔体积比为103070MMOL/ML，然后在2040条件下搅说明书CN104193742A2/31页5拌515MIN后，加入醛类化合物并在2040下搅拌反应1224H，醛类化合物与7氮杂吲哚的摩尔比为51510，然后过滤，滤饼用乙酸乙酯/石油醚重结晶得醇A；0011将醇A加入到乙酸乙酯中，醇A与乙酸乙酯的摩尔体积比为1080120MMOL/ML，醇A溶解后加入对甲苯亚磺酸和对甲苯磺酸，对甲苯亚磺酸与醇A的摩尔比为101510，对甲苯磺酸与醇A。

11、的摩尔比为102010，然后在2040下搅拌反应1830H后，过滤，滤饼用乙酸乙酯/石油醚重结晶得31芳砜烷基7氮杂吲哚1；0012B3烷基取代7氮杂吲哚化合物的合成0013往31芳砜烷基7氮杂吲哚1中加入碳酸钾或氢氧化钠，然后再加入亲核试剂，碳酸钾或氢氧化钠与31芳砜烷基7氮杂吲哚1的摩尔比为101510，亲核试剂与31芳砜烷基7氮杂吲哚1的摩尔比为101510，然后在4065下搅拌反应136H，然后使用乙酸乙酯/石油醚进行柱层析的到3烷基取代7氮杂吲哚化合物。0014步骤A中，优先将四甲基胍加入到7氮杂吲哚的水悬浮液中，四甲基胍与7氮杂吲哚的摩尔比为1510，7氮杂吲哚与水的摩尔体积比为1。

12、050MMOL/ML，然后在30条件下搅拌10MIN后，加入醛类化合物并在30下搅拌反应18H，醛类化合物与7氮杂吲哚的摩尔比为1010，然后过滤，滤饼用乙酸乙酯/石油醚重结晶得醇A。0015步骤A中，所述的醛类化合物是苯甲醛、4甲氧基苯甲醛、3甲氧基苯甲醛、2甲氧基苯甲醛、4氯苯甲醛、3氯苯甲醛、2氯苯甲醛、4氟苯甲醛、3氟苯甲醛、3三氟甲基苯甲醛或吡啶2甲醛。0016步骤A中，优先将醇A加入到乙酸乙酯中，醇A与乙酸乙酯的摩尔体积比为10100MMOL/ML，醇A溶解后加入对甲苯亚磺酸和对甲苯磺酸，对甲苯亚磺酸与醇A的摩尔比为1210，对甲苯磺酸与醇A的摩尔比为1510，然后在30下搅拌反应。

13、24H后，过滤，滤饼用乙酸乙酯/石油醚重结晶得31芳砜烷基7氮杂吲哚1。0017步骤B中，碳酸钾或氢氧化钠与31芳砜烷基7氮杂吲哚1的摩尔比为1210，亲核试剂与31芳砜烷基7氮杂吲哚1的摩尔比为1210。0018步骤B中，所述的亲核试剂为碳亲核试剂、氮亲核试剂、氧亲核试剂或硫亲核试剂中的一种。所述的碳亲核试剂为蒽酮、乙酰丙酮、1,3二苯基1,3丙二酮或丙二腈，所述的氮亲核试剂为苯胺、4甲氧基苯胺、3甲氧基苯胺、2甲氧基苯胺、4甲基苯胺、4氯苯胺、3氯苯胺或正丁胺，所述的氧亲核试剂为甲醇或乙醇，所述的硫亲核试剂为对甲苯硫酚。0019步骤A中，所述的乙酸乙酯/石油醚混合物中乙酸乙酯与石油醚的体积。

14、比为146。0020步骤B中，所述的乙酸乙酯/石油醚混合物中乙酸乙酯与石油醚的体积比为125。0021本发明的积极效果如下0022本发明在简单的反应条件下，方便高效地合成了各种结构的3烷基取代7氮杂吲哚化合物。具体实施方式0023下面的实施例是对本发明的进一步详细描述。说明书CN104193742A3/31页60024实施例10025一、31芳砜烷基7氮杂吲哚1的合成0026将四甲基胍15MMOL加入到7氮杂吲哚10MMOL的水50ML悬浮液中。在30条件下搅拌10分钟后，加入相应的醛10MMOL并在30下搅拌反应18H。过滤，滤饼用乙酸乙酯/石油醚重结晶得醇A。将A10MMOL加入到乙酸乙酯。

15、100ML中，溶解后加入对甲苯亚磺酸12MMOL和对甲苯磺酸15MMOL，在30下搅拌反应24H后，过滤，滤饼用乙酸乙酯/石油醚重结晶得31芳砜烷基7氮杂吲哚1，产物经氢核磁共振谱1HNMR、碳核磁共振谱13CNMR及高分辨质谱HRMS所确证。0027DD,J79,47HZ,1H,563S,1H,235S,3H；13CNMR100MHZ,CDCL31477,1445,1427,1350,1330,1301,1293,1290,1288,1286,1285,1261,1201,1162,1065,692,216；HRMSESICALCDFORC21H19N2O2SMH3631167,FOUND3。

16、6311620028620S,1H,574S,1H,370S,3H,227S,3H；13CNMR100MHZ,DMSO1569,1483,1445,1437,1359,1304,1303,1296,1289,1272,1269,1222,1209,1197,1162,1116,1055,590,561,214；HRMSESICALCDFORC22H21N2O2SMH3931273,FOUND393127800291H,623S,1H,368S,3H,228S,3H；13CNMR100MHZ,DMSO1594,1483,1444,1436,1说明书CN104193742A4/31页7360,13。

17、57,1298,1297,1289,1279,1267,1227,1196,1165,1160,1140,1060,669,555,214；HRMSESICALCDFORC22H21N2O2SMH3931273,FOUND3931255003080HZ,1H,635S,1H,351S,3H,230S,3H；13CNMR101MHZ,DMSO1569,1483,1445,1437,1359,1304,1303,1296,1289,1272,1269,1222,1209,1197,1162,1116,1055,590,561,214；HRMSESICALCDFORC22H21N2O2SMH3931。

18、273,FOUND3931256003181HZ,2H,702DD,J79,47HZ,1H,634S,1H,228S,3H；13CNMR100MHZ,DMSO1470,1447,1426,13562,1336,1331,1324,1298,1290,1289,1288,1272,1202,1161,1060,659,214；HRMSESICALCDFORC21H18CLN2O2SMH3970778,FOUND39707710032J81HZ,2H,702DD,J79,47HZ,1H,634S,1H,227S,3H；13CNMR100MHZ,DMSO1481,1447,1437,1364,135。

19、5,1333,1307,1304,1298,1291,1289,1288,1277,1268,1195,1161,1054,660,214；HRMSESICALCDFORC21H18CLN2O2SMH3970778,FOUND39707650033说明书CN104193742A5/31页8DD,J159,72HZ,2H,726D,J80HZ,2H,705DD,J79,47HZ,1H,638S,1H,228S,3H；13CNMR100MHZ,DMSO1478,1446,1434,1351,1337,1314,1309,1303,1296,1294,1285,1276,1267,1266,1190。

20、,1159,1044,626,211；HRMSESICALCDFORC21H18CLN2O2SMH3970778,FOUND39707770034T,J88HZ,2H,702DD,J79,47HZ,1H,630S,1H,226S,3H；13CNMR100MHZ,DMSO1624D,J2454HZ,1481,1446,1436,1357,1327,1326,1303D,J30HZ,1297,1289,1279,1267,1196,1161,1157,1155,1059,660,214；HRMSESICALCDFORC21H18FN2O2SMH3811073,FOUND3811089003576H。

21、Z,2H,714T,J76HZ,1H,703DD,J69,47HZ,1H,637S,1H,226S,3H；13CNMR100MHZ,DMSO1622D,J2438HZ,1482,1446,1437,1368D,J76HZ,1357,1307D,J83HZ,1297,1289,1277,1268,1267D,J24HZ,1196,1174,1172,116,1158,1156,1055,662,214；HRMSESICALCDFORC21H18FN2O2SMH3811073,FOUND38110630036说明书CN104193742A6/31页91H,753D,J81HZ,2H,724D,J8。

22、1HZ,2H,703DD,J79,47HZ,1H,648S,1H,226S,3H；13CNMR100MHZ,DMSO1481,1448,1438,1355,1353,1343,1300,1298,1289,1278,1273T,J4HZ,1268,1255T,J4HZ,1195,1162,1052,661,214；HRMSESICALCDFORC22H17F3N2O2SNAMNA4530860,FOUND45308710037T,J80HZ,1H,721D,J80HZ,2H,703DD,J78,47HZ,1H,634S,1H,228S,3H；13CNMR100MHZ,DMSO1537,1496。

23、,1482,1445,1434,1372,1355,1295,1292,1283,1281,1260,1237,1200,1160,1045,695,214；HRMSESICALCDFORC20H18N3O2SMH3641120,FOUND36411320038二、3烷基取代7氮杂吲哚化合物3和5的合成0039将碳酸钾012MMOL加入到31芳砜烷基7氮杂吲哚101MMOL和胺2或对甲苯硫酚4012MMOL的氯仿12ML溶液中，在65下搅拌反应36H。柱层析乙酸乙酯/石油醚1513得到相应的3烷基取代7氮杂吲哚化合物3或5，产物经氢核磁共振谱1HNMR、碳核磁共振谱13CNMR及高分辨质谱HR。

24、MS所确证。00400041说明书CN104193742A7/31页102H,721714M,2H,697DD,J78,47HZ,1H,662S,4H,595D,J71HZ,1H,575D,J71HZ,1H,357S,3H；13CNMR100MHZ,DMSO1512,1492,1443,1430,1428,1287,1279,1276,1271,1239,1186,1171,1155,1148,1147,557,554；HRMSESICALCDFORC21H19N3ONAMNA3521426,FOUND352142100422H,729DD,J133,61HZ,1H,709701M,3H,62。

25、7DD,J133,82HZ,2H,619S,1H,583D,J36HZ,1H,438D,J39HZ,1H,371S,3H；13CNMR100MHZ,CDCL31607,1493,1488,1428,1422,1299,1287,1281,1274,1273,1240,1189,1170,1157,1065,1027,995,559,550；HRMSESICALCDFORC21H19N3ONAMNA3521426,FOUND35214280043M,2H,703696M,1H,681D,J76HZ,1H,665T,J74HZ,1H,659647M,2H,585S,1H,499S,1H,376S,。

26、3H；13CNMR100MHZ,DMSO1492,1470,1436,1432,1374,1289,1275,1274,1273,1241,1213,1183,1169,1166,1158,1113,1102,559,550；HRMSESICALCDFORC21H20N3OMH3301608,FOUND33016180044说明书CN104193742A108/31页1170HZ,1H,705DD,J82,54HZ,2H,697D,J80HZ,2H,656D,J81HZ,2H,580S,1H,383S,1H,224S,3H；13CNMR100MHZ,CDCL31492,1452,1426,14。

27、25,1297,1287,1283,1274,1273,1268,1240,1191,1173,1157,1135,562,204；HRMSESIM/ZCALCDFORC21H19N3NAMNA3361477,FOUND336150000451H,715T,J78HZ,2H,706DD,J73,48HZ,2H,672T,J73HZ,1H,662D,J79HZ,2H,583S,1H；13CNMR100MHZ,CDCL31488,1474,1424,1421,1292,1287,1285,1275,1273,1241,1192,1177,1173,1158,1134,559；HRMSESICALC。

28、DFORC20H18N3MH3001501,FOUND30015210046734729M,1H,711701M,4H,653D,J86HZ,2H,578S,1H,435S,1H；13CNMR100MHZ,CDCL31490,1459,1428,1417,1290,1288,1282,1276,1272,1240,1223,1189,1168,1159,1145,560；HRMSESICALCDFORC20H16CLN3NAMNA3560930,FOUND3560917说明书CN104193742A119/31页120047T,J72HZ,1H,709697M,3H,667D,J79HZ,1H。

29、,660S,1H,648D,J81HZ,1H,580D,J47HZ,1H,440D,J44HZ,1H；13CNMR100MHZ,CDCL31491,1484,1433,1415,1349,1302,1288,1280,1276,1272,1237,1186,1176,1168,1160,1131,1115,558；HRMSESICALCDFORC20H17CLN3MH3341111,FOUND33411090048741T,J72HZ,2H,734D,J70HZ,1H,706DD,J75,47HZ,1H,584D,J55HZ,1H,280D,J72HZ,2H,177164M,2H,122DT,。

30、J144,72HZ,2H,080T,J73HZ,3H；13CNMR100MHZ,DMSO1484,1438,1374,1293,1290,1284,1275,1255,1182,1162,1099,580,461,276,199,139；HRMSESICALCDFORC18H21N3NAMNA3021633,FOUND30216370049D,J85HZ,2H,657D,J85HZ,2H,569S,1H,404S,1H,381S,3H,373S,3H；13CNMR100MHZ,CDCL31588,1521,1493,1429,1419,1347,1284,1281,1236,1188,1177。

31、,1157,1148,1146,1140,562,558,553；HRMSESICALCDFORC22H21N3O2NAMNA3821531,FOUND3821524说明书CN104193742A1210/31页1300501H,706DT,J80,69HZ,4H,683DD,J81,21HZ,1H,675D,J89HZ,2H,658D,J89HZ,2H,571S,1H,409S,1H,378S,3H,373S,3H；13CNMR100MHZ,CDCL31599,1522,1493,1444,1428,1418,1297,1282,1238,1197,1189,1172,1157,1148,1。

32、146,1130,1125,568,558,552；HRMSESICALCDFORC22H21N3O2NAMNA3821531,FOUND38215310051D,J92HZ,2H,698690M,2H,673D,J88HZ,2H,658D,J88HZ,2H,614S,1H,530S,1H,382S,3H,372S,3H；13CNMR100MHZ,CDCL31569,1521,1489,1423,1419,1304,1286,1284,1279,1236,1208,1195,1171,1156,1148,11461108,558,556,504；HRMSESICALCDFORC22H21N3O。

33、2NAMNA3821531,FOUND38215250052J84HZ,2H,706DD,J79,48HZ,1H,701D,J11HZ,1H,675D,J89HZ,2H,655D,J89HZ,2H,571D,J21HZ,1H,406D,J28HZ,1H,373S,3H；13CNMR100MHZ,CDCL31523,1493,1430,1415,1411,1330,1288,1286,1281,1238,1187,1170,1158,1149,1146,562,558；HRMSESIM/ZCALCDFORC21H19CLN3OMH3641217,FOUND36411970053说明书CN1041。

34、93742A1311/31页14DD,J129,57HZ,2H,710701M,2H,676D,J88HZ,2H,656D,J88HZ,2H,570S,1H,407S,1H,373S,3H；13CNMR100MHZ,CDCL31524,1491,1448,1432,1414,1346,1299,1280,1276,1274,1254,1237,1186,1169,1159,1149,1146,564,558；HRMSESICALCDFORC21H18CLN3ONAMNA3861038,FOUND38610110054732723M,2H,707DD,J78,48HZ,1H,696S,1H,67。

35、5D,J88HZ,2H,653D,J88HZ,2H,614S,1H,414S,1H,373S,3H；13CNMR100MHZ,CDCL31523,1491,1431,1413,1395,1335,1299,1286,1284,1281,1272,12391189,1159,1157,1149,1144,557,533；HRMSESICALCDFORC21H18CLN3ONAMNA3861038,FOUND386101600554H,675D,J89HZ,2H,656D,J88HZ,2H,572S,1H,373S,3H；13CNMR100MHZ,CDCL31633,1608,1523,1492,。

36、1429,1416,1382D,J30HZ,1288D,J80HZ,1281,1237,1188,1173,1158,1156,1154,1148,1146,561,558；HRMSESICALCDFORC21H19FN3OMH3481512,FOUND34815250056说明书CN104193742A1412/31页15712702M,2H,698S,1H,675D,J88HZ,2H,656D,J88HZ,2H,573S,1H,408S,1H,373S,3H；13CNMR100MHZ,CDCL31644,1620,1523,1492,1454D,J60HZ,1431,1415,1301D,。

37、J80HZ,1281,1237,1229D,J30HZ,1187,1169,1159,1149,1146,1143D,J120HZ,1141D,J120HZ,564D,J20HZ,558；HRMSESICALCDFORC21H19FN3OMH3481512,FOUND34815130057D,J77HZ,1H,748T,J77HZ,1H,707DD,J79,48HZ,1H,699S,1H,676D,J88HZ,2H,655D,J88HZ,2H,579S,1H,409S,1H,373S,3H；13CNMR100MHZ,CDCL31525,1492,1437,1432,1414,1306,1291。

38、,1280,1243Q,J40,1241Q,J40HZ1238,1186,1168,1159,1149,1146,566,557；HRMSESICALCDFORC22H19F3N3OMH3981480,FOUND39814810058D,J78HZ,1H,718S,2H,704DD,J79,48HZ,1H,673D,J89HZ,2H,664D,J89HZ,2H,584S,1H,371S,3H；13CNMR100MHZ,CDCL31616,1523,1493,1492,1429,1416,1369,1282,1235,1222,1216,1188,1163,1158,1150,1148,580,。

39、557；HRMSESICALCDFORC20H19N4OMH3311559,FOUND33115340059说明书CN104193742A1513/31页16719D,J80HZ,2H,705DD,J79,48HZ,1H,701D,J79HZ,2H,570S,1H,228S,3H；13CNMR100MHZ,CDCL31492,1427,1411,1370,1323,1317,1295,1287,1285,1284,1273,1245,1193,1156,1148,509,211；HRMSESICALCDFORC21H19N2SMH3311269,FOUND33112900060685D,J86。

40、HZ,2H,568S,1H,380S,3H,228S,3H；13CNMR100MHZ,CDCL31587,1494,1427,1368,1333,1325,1315,1295,1287,1245,1193,1155,1151,1138,553,502,211；HRMSESICALCDFORC22H21N20SMH3611375,FOUND36113980061J81,21HZ,1H,568S,1H,376S,3H,228S,3H；13CNMR100MHZ,CDCL31597,1493,1428,1426,1370,1324,1316,1296,1294,1287,1246,1209,1194,。

41、1155,1146,1141,1128,552,508,211；HRMSESICALCDFORC22H21N20SMH3611375,FOUND36113730062说明书CN104193742A1614/31页173H,707702M,1H,700D,J80HZ,2H,696686M,2H,629S,1H,382S,3H,227S,3H；13CNMR100MHZ,CDCL31564,1491,1429,1363,1331,1307,1295,1294,1284,1283,1242,1208,1194,1156,1152,1108,557,422,210；HRMSESICALCDFORC22H。

42、21N20SMH3611375,FOUND36113970063718D,J80HZ,2H,707DD,J79,48HZ,1H,702D,J79HZ,2H,565S,1H,229S,3H；13CNMR100MHZ,CDCL31492,1428,1398,1373,1330,1320,1317,1298,1297,1287,1286,1246,1192,1156,1142,503,211；HRMSESICALCDFORC21H18CLN2SMH3650879,FOUND365,09000064708DD,J79,48HZ,1H,702D,J79HZ,2H,564S,1H,229S,3H；13CN。

43、MR100MHZ,CDCL31492,1433,1429,1374,1343,1320,1316,1297,1286,1285,1275,1266,1245,1192,1157,1141,505211；HRMSESICALCDFORC21H18CLN2SMH3650879FOUND36508790065说明书CN104193742A1715/31页181H,728716M,5H,710699M,3H,627S,1H,228S,3H；13CNMR100MHZ,CDCL31493,1428,1386,1370,1334,1321,1311,1302,1296,1285,1284,1271,1248。

44、,1193,1157,1139,464,211；HRMSESICALCDFORC21H18CLN2SMH3650879,FOUND36508930066J79,48HZ,1H,704696M,4H,568S,1H,229S,3H；13CNMR100MHZ,CDCL31631,1607,1493,1426,1372,1370D,J30HZ,1319,1300D,J80HZ,1296,1287,1246,1193,1155D,J190HZ,1152,1145,502,211；HRMSESICALCDFORC21H18FN2SMH1491175,FOUND3491198006778HZ,2H,695。

45、T,J82HZ,1H,568S,1H,229S,3H；13CNMR100MHZ,CDCL31641,1616,1493,1428,1374,1320,1317,1298D,J80,1296,1286,1246,1241D,J30HZ,1192,1156D,J17HZ,1153,1144,1141,505,211；HRMSESICALCDFORC21H18FN2SMH1491175,FOUND3491194说明书CN104193742A1816/31页1900681H,741T,J77HZ,1H,728S,1H,718D,J80HZ,2H,709DD,J79,48HZ,1H,702D,J79HZ。

46、,2H,572S,1H,229S,3H；13CNMR100MHZ,CDCL31493,1428,1424,1377,1325,1317,1312,1297,1289,1286,1252Q,J40HZ,1247,1241Q,J40HZ,1192,1157,1138,508,211；HRMSESICALCDFORC22H18F3N2SMH3991143,FOUND39911550069745D,J78HZ,1H,731S,1H,722712M,3H,705DD,J79,48HZ,1H,699D,J79HZ,2H,582S,1H,227S,3H；13CNMR100MHZ,CDCL31606,1492。

47、,1491,1428,1372,1367,1321,1317,1296,1286,1244,1227,1222,1192,1156,1135,526,211；HRMSESICALCDFORC20H18N3SMH3321221,FOUND33211940070三、3烷基取代7氮杂吲哚化合物7的合成0071将碳酸钾012MMOL加入到31芳砜烷基7氮杂吲哚101MMOL和醇612ML的溶液中，在65下搅拌反应36H。柱层析乙酸乙酯/石油醚1513得到相应的3烷基取代7氮杂吲哚化合物7，产物经氢核磁共振谱1HNMR、碳核磁共振谱13CNMR及高分辨质谱HRMS所确证。00720073说明书CN104。

48、193742A1917/31页2052HZ,2H,569S,1H,377347M,2H,131T,J70HZ,3H；13CNMR100MHZ,CDCL31494,1426,1418,1287,1283,1275,1271,1238,1192,1165,1157,767,643,155；HRMSESICALCDFORC16H17N2OMH2531341,FOUND25313450074382S,3H,357DD,J70,26HZ,2H,129T,J70HZ,3H；13CNMR100MHZ,CDCL31591,1493,1429,1338,1287,1284,1234,1190,1170,1158。

49、,1137,767,641,553,154；HRMSESICALCDFORC17H19N2O2MH2831447,FOUND283143700753H,360Q,J69HZ,2H,130T,J70HZ,3H；13CNMR100MHZ,CDCL31597,1493,1434,1427,1293,1287,1237,1196,1191,1165,1158,1130,1126,767,643,552,155；HRMSESICALCDFORC17H19N2O2MH2831447,FOUND283149300761H,3说明书CN104193742A2018/31页2180S,3H,366355M,2H,129T,J70HZ,3H；13CNMR100MHZ,CDCL31569,1491,1427,1301,1285,1284,1273,1233,1207,1193,1165,1157,1105。

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