本发明涉及医药技术领域，具体涉及2,3-稠环吲哚啉衍生物及其合成方法和应用。
背景技术：
吲哚生物碱是一类重要的天然产物，由于其数目众多，结构复杂，往往具有显著的生理活性，因此一直备受合成化学家以及药物化学家的青睐。
稠环吲哚啉骨架，特别是2，3-稠环吲哚啉是吲哚啉生物碱中广泛存在的核心结构，在化合物的生理活性及药理活性中起到了决定性作用，2，3-稠环吲哚啉核心骨架的成功构建是这类生物碱全合成的重点和难点，因此2，3-稠环吲哚啉骨架的高效构建一直是有机合成中的热点和难点之一。构建这类骨架的策略可以通过钯催化的串联反应(zhang,g.z.；catalano,v.j.；zhang,l.m.j.am.chem.soc.2007,129,11358-11359.)，氧化偶联、分子内环化反应(zuo,z.w.；xie,w.q.；ma,d.w.j.am.chem.soc.2010,132,13226-13228)等，但这些方法都存在底物受限，官能团兼容性差，步骤繁琐以及使用原料较复杂等不足。
技术实现要素：
本发明要解决的技术问题是提供一系列结构新颖的2,3-稠环吲哚啉衍生物，以及它们的合成方法和应用。
本发明涉及下述式(i)所示化合物或其药学上可接受的盐：
其中：
r1表示氢、c1～4的烷基、c1～4的烷氧基、c1～4的全氟烷基或卤原子，或者是未取代、单取代、二取代、三取代、四取代或五取代的苯基，或者是未取代的呋喃基，或者是未取代的噻吩基，或者是未取代的萘基；其中，取代基为c1～4的烷氧基、c1～4的全氟烷基、c1～4的烷基、氰基或卤原子；
r2表示氢、c1～4的烷基、c1～4的烷氧基、c1～4的全氟烷基或卤原子，或者是未取代、单取代、二取代、三取代、四取代或五取代的苯基，或者是未取代的呋喃基，或者是未取代的噻吩基，或者是未取代的萘基；其中，取代基为c1～4的烷氧基、c1～4的全氟烷基、c1～4的烷基、氰基或卤原子；
r3表示氢、c1～8的烷基、c1～6的烷氧基或c1～4的全氟烷基，或者是未取代、单取代或二取代的苯基；其中，取代基为c1～4的烷氧基、c1～4的全氟烷基、c1～6的烷基或卤原子；
r4表示氢、c1～8的烷基、c1～6的烷氧基或c1～4的全氟烷基，或者是未取代、单取代或二取代的苯基；其中，取代基为c1～4的烷氧基、c1～4的全氟烷基、c1～6的烷基或卤原子；
x表示氧或氮原子；
n＝1、2或3。
上述化合物中：
r1进一步优选为氢或c1～4烷基，或者是未取代、单取代或二取代的苯基；
r2进一步优选为氢或c1～4烷基，或者是未取代、单取代或二取代的苯基；
r3进一步优选为氢或c1～4烷基，或者是未取代、单取代或二取代的苯基；
r4进一步优选为氢或c1～4烷基，或者是未取代、单取代或二取代的苯基。
上述式(i)所示化合物的合成方法，主要包括以下步骤：取如下式(ii)所示化合物置于有机溶剂中，在氧气存在的条件下反应，制得目标物粗品；
其中：
r1表示氢、c1～4的烷基、c1～4的烷氧基、c1～4的全氟烷基或卤原子，或者是未取代、单取代、二取代、三取代、四取代或五取代的苯基，或者是未取代的呋喃基，或者是未取代的噻吩基，或者是未取代的萘基；其中，取代基为c1～4的烷氧基、c1～4的全氟烷基、c1～4的烷基、氰基或卤原子；
r2表示氢、c1～4的烷基、c1～4的烷氧基、c1～4的全氟烷基或卤原子，或者是未取代、单取代、二取代、三取代、四取代或五取代的苯基，或者是未取代的呋喃基，或者是未取代的噻吩基，或者是未取代的萘基；其中，取代基为c1～4的烷氧基、c1～4的全氟烷基、c1～4的烷基、氰基或卤原子；
r3表示氢、c1～8的烷基、c1～6的烷氧基或c1～4的全氟烷基，或者是未取代、单取代或二取代的苯基；其中，取代基为c1～4的烷氧基、c1～4的全氟烷基、c1～6的烷基或卤原子；
r4表示氢、c1～8的烷基、c1～6的烷氧基或c1～4的全氟烷基，或者是未取代、单取代或二取代的苯基；其中，取代基为c1～4的烷氧基、c1～4的全氟烷基、c1～6的烷基或卤原子；
x表示氧或氮原子；
n＝1、2或3。
上述合成方法中，r1、r2、r3和r4的优先选择如前所述。
上述合成方法中，式(ii)所示化合物为n-芳基α,β-不饱和硝酮衍生物，其可参考现有文献(xiao-panma,wei-minshi,xue-lingmo,xiao-huali,liang-guili,cheng-xuepan,bochen*,gui-fasu*anddong-liangmo*,j.org.chem.2015,80,10098-10107.)进行合成，也可自选设计合成路线进行合成，在此不再详述。
上述合成方法中，所述的有机溶剂可以是选自苯、甲苯、环己烷、石油醚、四氯化碳、四氢呋喃、乙酸乙酯、乙腈、乙醚、二氯甲烷、丙酮、三氯甲烷、正己烷和二氧六环中一种或两种以上的组合。当有机溶剂的选择为上述两种以上物质的组合时，它们的配比可以为任意配比。
上述合成方法中，反应一般选择在空气条件下进行，同时反应优选是在低于100℃的条件下进行，进一步优选是在常温至80℃的条件下进行。反应是否完全可采用tlc跟踪检测。根据申请人的经验，当反应在80℃条件下进行时，反应时间控制在5～20h较为适宜。
本发明所述的合成方法中，所述有机溶剂的用量以能够溶解参加反应的原料为宜，通常情况下，1mmol的式(ii)所示化合物通常用1～10ml的有机溶剂来溶解。
由上述方法制得的是式(i)化合物的粗品，可采用现有常规的纯化方法对其进行纯化以提高式(i)化合物的纯度。通常采用硅胶薄层色谱或硅胶柱层析，或者是重结晶的方式进行纯化，在层析时用的洗脱剂和重结晶时用的溶剂相同，可以是由石油醚和乙酸乙酯组成的混合溶剂，也可以是由正己烷和乙酸乙酯组成的混合溶剂。在前述混合溶剂中，石油醚和乙酸乙酯的体积比优选为50：1～10：1，正己烷和乙酸乙酯的体积比优选为50:1～10:1。
本发明还提供上述式(i)所示化合物或其药学上可接受的盐在制备抗肿瘤药物中的应用。
与现有技术相比，本发明提供了一系列结构新颖的2,3-稠环吲哚啉衍生物以及它们的合成方法和它们应用，申请人发现部分2,3-稠环吲哚啉衍生物具有一定的抗肿瘤活性。另一方面，本发明提供的合成方法简单易控，周期短，产率较高，不需无水无氧条件。
具体实施方式
下面结合具体实施例对本发明作进一步的详述,以更好地理解本发明的内容,但本发明并不限于以下实施例。
以下各实施例中涉及的n-芳基α,β-不饱和硝酮衍生物(即式(ii)所示化合物)参照下述合成路线进行合成：
其中：
r1表示氢、c1～4的烷基、c1～4的烷氧基、c1～4的全氟烷基或卤原子，或者是未取代、单取代、二取代、三取代、四取代或五取代的苯基，或者是未取代的呋喃基，或者是未取代的噻吩基，或者是未取代的萘基；其中，取代基为c1～4的烷氧基、c1～4的全氟烷基、c1～4的烷基、氰基或卤原子；
r2表示氢、c1～4的烷基、c1～4的烷氧基、c1～4的全氟烷基或卤原子，或者是未取代、单取代、二取代、三取代、四取代或五取代的苯基，或者是未取代的呋喃基，或者是未取代的噻吩基，或者是未取代的萘基；其中，取代基为c1～4的烷氧基、c1～4的全氟烷基、c1～4的烷基、氰基或卤原子；
r3表示氢、c1～8的烷基、c1～6的烷氧基或c1～4的全氟烷基，或者是未取代、单取代或二取代的苯基；其中，取代基为c1～4的烷氧基、c1～4的全氟烷基、c1～6的烷基或卤原子；
r4表示氢、c1～8的烷基、c1～6的烷氧基或c1～4的全氟烷基，或者是未取代、单取代或二取代的苯基；其中，取代基为c1～4的烷氧基、c1～4的全氟烷基、c1～6的烷基或卤原子；
x表示氧或氮原子；
n＝1、2或3。
具体的合成方法为：将α,β-不饱和肟底物s1(0.5mmol)和氢氧化钾(0.75mmol)置于反应管中，加入5ml四氯化碳，室温下搅拌5min，加入高价碘试剂s2(0.75mmol)，室温反应1-24h后，所得反应物减压除去溶剂，残渣上硅胶柱层析分离(石油醚/乙酸乙酯＝4：1～1：1，体积比)，得到目标产物1(即式(ii)所示化合物n-芳基α,β-不饱和硝酮)。
实施例1
按下述合成路线合成本发明所述的2,3-稠环吲哚啉衍生物。
2a:r1＝h,r2＝phch＝ch,r3＝h,r4＝h,n＝1；
2b:r1＝h,r2＝phch＝ch,r3＝4-ome,r4＝h,n＝1；
2c:r1＝h,r2＝phch＝ch,r3＝4-me,r4＝h,n＝1；
2d:r1＝h,r2＝phch＝ch,r3＝4-tbu,r4＝h,n＝1；
2e:r1＝h,r2＝phch＝ch,r3＝4-cl,r4＝h,n＝1；
2f:r1＝h,r2＝phch＝ch,r3＝4-f,r4＝h,n＝1；
2g:r1＝h,r2＝phch＝ch,r3＝4-cf3,r4＝h,n＝1；
2h:r1＝h,r2＝phch＝ch,r3＝4-co2me,r4＝h,n＝1；
2i:r1＝h,r2＝phch＝ch,r3＝3-ome,r4＝h,n＝1；
2j:r1＝h,r2＝phch＝ch,r3＝3-no2,r4＝h,n＝1；
2k:r1＝h,r2＝phch＝ch,r3＝3,5-me,r4＝h,n＝1；
2l:r1＝h,r2＝phch＝ch,r3＝2-me,r4＝h,n＝1；
2ab:r1＝h,r2＝(4-ome)c6h4ch＝ch,r3＝h,r4＝h,n＝1；
2ac:r1＝h,r2＝(4-me)c6h4ch＝ch,r3＝h,r4＝h,n＝1；
2ad:r1＝h,r2＝(4-f)c6h4ch＝ch,r3＝h,r4＝h,n＝1；
2ae:r1＝h,r2＝(4-cf3)c6h4ch＝ch,r3＝h,r4＝h,n＝1；
2af:r1＝h,r2＝(3-ome)c6h4ch＝ch,r3＝h,r4＝h,n＝1；
2ag:r1＝h,r2＝(3-br)c6h4ch＝ch,r3＝h,r4＝h,n＝1；
2ah:r1＝h,r2＝(2-br)c6h4ch＝ch,r3＝h,r4＝h,n＝1；
2ai:r1＝h,r2＝(2-furyl)ch＝ch,r3＝h,r4＝h,n＝1；
2aj:r1＝h,r2＝me,r3＝h,r4＝h,n＝1；
2ak:r1＝h,r2＝me,r3＝h,r4＝me,n＝1；
2al:r1＝h,r2＝phch＝ch,r3＝h,r4＝ph,n＝1；
2am:r1＝4-f,r2＝phch＝ch,r3＝h,r4＝h,n＝1；
2an:r1＝3-br,r2＝me,r3＝h,r4＝h,n＝1；
2ao:r1＝3,5-me,r2＝me,r3＝h,r4＝h,n＝1；
2ap:r1＝h,r2＝h,r3＝h,r4＝h,n＝1；
2aq:r1＝h,r2＝h,r3＝h,r4＝h,n＝1,x＝nh；
2ar:r1＝h,r2＝h,r3＝h,r4＝h,n＝2；
2as:r1＝h,r2＝h,r3＝h,r4＝h,n＝3。
取n-芳基α,β-不饱和硝酮底物1(0.2mmol)置于反应管中，加入2ml有机溶剂(其中目标物2a-2l采用的有机溶剂为四氯化碳，目标物2af-2am采用的有机溶剂分别为苯、甲苯、环己烷、石油醚、四氢呋喃、乙酸乙酯、乙腈和乙醚，目标物2an-2as采用的有机溶剂均为苯和四氢呋喃按1：1的体积比组成的混合溶剂)在80℃下搅拌反应5-20h，所得反应物减压除去溶剂，残渣上硅胶柱层析分离(石油醚/乙酸乙酯＝50：1～10：1，体积比)，得到目标产物2。不同的目标产物及其表征如下：
2a：固体,50mg,70％yield；mp161–162℃.1hnmr(400mhz,cdcl3):δ9.50(s,1h),7.29(d,j＝7.6hz,2h),7.24(t,j＝7.2hz,2h),7.19–7.15(m,1h),7.11(d,j＝7.6hz,1h),7.07–7.03(m,j＝6.8hz,3h),6.90–6.86(m,2h),6.76(t,j＝6.8hz,2h),6.63(d,j＝8.0hz,1h),6.40(d,j＝15.6hz,1h),4.66(d,j＝12.8hz,1h),4.30(brs,1h),4.27(d,j＝12.4hz,1h)；13cnmr(100mhz,cdcl3):δ197.0,154.2,149.9,135.7,132.7,130.1,129.1,129.0,128.6,128.2,127.4,126.9,126.8,124.6,122.7,122.1,120.3,117.6,110.8,69.9,63.0,61.6.ir(thinfilm)3367,2925,2848,1709,1602,1482,1214,1059,755cm-1；hrms(esi)m/zcalcdforc24h20no2[m+h]+:354.1494,found:354.1495.
2b：固体,52mg,67％yield；mp51–52℃.1hnmr(400mhz,cdcl3):δ9.51(s,1h),7.29(d,j＝7.2hz,2h),7.24–7.21(m,2h),7.19–7.15(m,1h),7.12(d,j＝7.6hz,1h),7.08–7.04(m,1h),6.90–6.86(m,2h),6.77(d,j＝8.4hz,1h),6.64(d,j＝6.4hz,3h),6.40(d,j＝16.0hz,1h),4.65(d,j＝16.4hz,1h),4.28(d,j＝12.4hz,1h),4.10(brs,1h),3.64(s,3h).13cnmr(100mhz,cdcl3):δ202.2,154.6,144.3,139.6,136.2,131.5,129.8,128.6,128.5,128.4,127.9,127.7,127.5,126.6,122.1,117.5,115.4,111.9,110.4,71.0,66.5,64.9,55.3.ir(thinfilm)3433,3025,2924,1709,1638,1459,1272,752cm-1；hrms(esi)m/zcalcdforc25h22no3[m+h]+:384.1600,found:384.1594.
2c：固体,46mg,63％yield；mp186–188℃.1hnmr(400mhz,cdcl3):δ9.49(s,1h),7.30(d,j＝7.6hz,2h),7.25–7.15(m,3h),7.11–7.04(m,2h),6.90–6.86(m,4h),6.77(d,j＝8.4hz,1h),6.55(d,j＝9.2hz,1h),6.40(d,j＝15.6hz,1h),4.66(d,j＝12.4hz,1h),4.29(d,j＝12.8hz,1h),4.20(brs,1h),2.17(s,3h).13cnmr(100mhz,cdcl3):δ197.1,154.2,147.6,135.8,132.6,130.7,129.9,129.3,128.9,128.6,128.1,127.5,127.1,126.8,125.1,122.8,122.1,117.6,110.7,70.0,62.7,61.4,20.6.ir(thinfilm)3360,3028,2923,1709,1614,1493,1263,821,748cm-1；hrms(esi)m/zcalcdforc25h22no2[m+h]+:368.1651,found:368.1664.
2d：固体,49mg,60％yield；mp163–164℃.1hnmr(400mhz,cdcl3):δ9.50(s,1h),7.30(d,j＝7.2hz,2h),7.25–7.21(m,2h),7.19–7.16(m,1h),7.11–7.03(m,4h),6.89–6.85(m,2h),6.77(d,j＝8.0hz,1h),6.59(d,j＝8.4hz,1h),6.41(d,j＝16.0hz,1h),4.67(d,j＝12.4hz,1h),4.31(d,j＝12.4hz,1h),4.19(brs,1h),1.18(s,9h).13cnmr(100mhz,cdcl3):δ197.3,154.3,147.5,143.6,135.8,132.5,129.5,128.9,128.6,128.1,127.5,127.2,127.1,126.8,122.4,122.0,121.3,117.7,110.4,70.0,63.1,61.9,34.3,31.5.ir(thinfilm)3376,3033,2960,1716,1613,1490,1270,824,749cm-1；hrms(esi)m/zcalcdforc28h28no2[m+h]+:410.2120,found:410.2115.
2e：固体,41mg,53％yield；mp167–168℃.1hnmr(400mhz,cdcl3):δ9.50(s,1h),7.29–7.17(m,5h),7.10(t,j＝7.2hz,2h),7.02(d,j＝8.4hz,2h),6.90–6.84(m,2h),6.79(d,j＝8.0hz,1h),6.55(d,j＝8.0hz,1h),6.38(d,j＝15.6hz,1h),4.62(d,j＝12.4hz,1h),4.32(brs,1h),4.28(d,j＝15.6hz,1h).13cnmr(100mhz,cdcl3):δ196.4,154.2,148.4,135.5,133.0,130.1,129.2,128.7,128.6,128.3,127.4,126.8,126.5,125.0,124.9,124.6,122.3,117.7,111.7,70.4,62.8,61.6.ir(thinfilm)3360,2923,2854,1713,1602,1482,756,690cm-1；hrms(esi)m/zcalcdforc24h19clno2[m+h]+:388.1104,found:388.1087.
2f：固体,45mg,60％yield；mp169–170℃.1hnmr(400mhz,cdcl3):δ9.52(s,1h),7.30(d,j＝7.2hz,2h),7.26(t,j＝7.2hz,2h),7.20–7.18(m,1h),7.12–7.06(m,2h),6.91–6.86(m,2h),6.80–6.74(m,3h),6.57(dd,j＝8.4hz,4.0hz,1h),6.39(d,j＝16.0hz,1h),4.63(d,j＝12.4hz,1h),4.28(d,j＝12.4hz,1h),4.20(brs,1h).13cnmr(100mhz,cdcl3):δ196.7,158.8(d,j＝237hz),154.2,145.9,135.6,132.9,129.1,128.8,128.6,128.3,127.4,126.8,126.7,124.4(d,j＝8hz),122.3,117.7,116.8(d,j＝23.3hz),112.1(d,j＝24.1hz),111.4(d,j＝8.1hz),70.6,62.8,61.8.ir(thinfilm)3359,2925,2853,1708,1608,1487,1221,757cm-1；hrms(esi)m/zcalcdforc24h19fno2[m+h]+:372.1400,found:372.1385.
2g：固体,34mg,40％yield；mp122–123℃.1hnmr(400mhz,cdcl3):δ9.53(s,1h),7.33–7.18(m,7h),7.12–7.08(m,2h),6.93–6.89(m,1h),6.87–6.79(m,2h),6.68(d,j＝8.0hz,1h),6.40(d,j＝16.0hz,1h),4.64(d,j＝12.4hz,1h),4.59(brs,1h),4.33(d,j＝12.8hz,1h).13cnmr(100mhz,cdcl3):δ196.2,154.2,152.5,135.4,133.1,129.3,128.7,128.5,128.3,128.1,128.0,127.4,126.8,126.1,123.2,122.4,122.2,122.1,117.9,110.0,70.2,62.7,61.2.ir(thinfilm)3339,2923,2853,1710,1623,1274,1104,758cm-1；hrms(esi)m/zcalcdforc25h19f3no2[m+h]+:422.1368,found:422.1368.
2h：固体,40mg,49％yield；mp73–74℃.1hnmr(400mhz,cdcl3):δ9.51(s,1h),7.82(d,j＝8.0hz,1h),7.75(s,1h),7.30–7.18(m,5h),7.11–7.07(m,2h),6.91–6.83(m,2h),6.79(d,j＝8.4hz,1h),6.63(d,j＝8.0hz,1h),6.39(d,j＝16.0hz,1h),4.71(brs,1h),4.67(d,j＝12.4hz,1h),4.33(d,j＝12.8hz,1h),3.77(s,3h).13cnmr(100mhz,cdcl3):δ196.2,166.5,154.2,153.7,135.4,133.0,132.9,129.3,128.7,128.4,128.0,127.4,126.8,126.6,126.2,122.8,122.3,122.0,117.9,109.6,70.4,63.1,61.2,51.7.ir(thinfilm)3345,3025,2924,1708,1518,1285,753cm-1；hrms(esi)m/zcalcdforc26h22no4[m+h]+:412.1549,found:412.1552.
2i：固体,48mg,63％yield；mp43–44℃.1hnmr(400mhz,cdcl3):δ9.48(s,1h),9.46(s,1h),7.30(d,j＝7.2hz,4h),7.24(t,j＝7.2hz,4h),7.19–7.16(m,2h),7.11–7.03(m,4h),6.95–6.83(m,6h),6.77(d,j＝8.0hz,2h),6.58(d,j＝7.6hz,1h),6.51(d,j＝7.6hz,1h),6.47–6.36(m,4h),4.97(d,j＝12.4hz,1h),4.65(d,j＝12.0hz,1h),4.28–4.19(m,4h),2.20(s,3h),2.16(s,3h).13cnmr(100mhz,cdcl3):δ197.0,196.3,155.0,154.2,150.2,150.0,140.4,137.0,135.8,133.0,132.6,130.1,129.2,129.0,128.9,128.8,128.6,128.5,128.2,128.1,127.4,127.3,127.2,127.0,126.9,126.8,126.7,124.3,122.8,122.1,122.0,121.2,119.8,119.5,117.7,117.5,111.6,108.6,70.4,70.0,63.0,62.9,62.6,61.4,21.3,18.5.ir(thinfilm)3368,3025,2924,1708,1614,1459,1272,752cm-1；hrms(esi)m/zcalcdforc25h22no3[m+h]+:384.1600,found:384.1583.
2j：固体,38mg,48％yield；mp187–188℃.1hnmr(400mhz,cdcl3):δ9.60(s,1h),7.43(d,j＝8.0hz,1h),7.28–7.18(m,6h),7.11(d,j＝7.6hz,2h),6.92–6.89(m,2h),6.83(d,j＝8.0hz,1h),6.72(d,j＝16.0hz,1h),6.72(d,j＝16.0hz,1h),4.61(brs,1h),4.60(d,j＝12.6hz,1h),4.54(d,j＝12.4hz,1h).13cnmr(100mhz,cdcl3):δ195.7,154.1,150.5,150.0,135.3,133.5,130.0,129.5,128.7,128.6,127.8,127.4,126.8,125.9,125.1,122.6,117.8,115.7,105.1,70.8,62.9,61.5.ir(thinfilm)3349,2923,2852,1716,1529,1351,802,759cm-1；hrms(esi)m/zcalcdforc24h19n2o2[m+h]+:399.1345,found:399.1339.
2k：固体,46mg,60％yield；mp96–97℃.1hnmr(400mhz,cdcl3):δ9.58(s,1h),7.42(d,j＝8.0hz,1h),7.26–7.17(m,4h),7.10(d,j＝7.6hz,3h),6.92–6.85(m,2h),6.80(d,j＝8.0hz,1h),6.72(d,j＝16.0hz,1h),6.70(d,j＝16.0hz,1h),4.65(brs,1h),4.60(d,j＝12.6hz,1h),4.52(d,j＝12.4hz,1h),2.06(s,3h),2.03(s,3h).13cnmr(100mhz,cdcl3):δ195.7,154.1,150.5,150.0,135.3,133.5,130.0,129.5,128.7,128.6,127.8,127.4,126.8,125.9,125.1,122.6,117.8,115.7,105.1,70.8,62.9,61.5,16.8,16.1.ir(thinfilm)3451,3032,2924,2850,1733,1606,1510,968,635cm-1；hrms(esi)m/zcalcdforc26h24no2[m+h]+:382.1807,found:382.1829.
2l：固体,50mg,68％yield；mp220–221℃.1hnmr(400mhz,cdcl3):δ9.50(s,1h),7.30(d,j＝7.6hz,2h),7.25–7.21(m,2h),7.19–7.13(m,2h),7.08–7.04(m,1h),6.89–6.86(m,4h),6.77(d,j＝8.0hz,1h),6.72(t,j＝7.6hz,1h),6.43(d,j＝16.0hz,1h),4.64(d,j＝12.4hz,1h),4.31(d,j＝12.4hz,1h),4.09(brs,1h),2.07(s,3h).13cnmr(100mhz,cdcl3):δ197.1,154.3,148.5,135.8,132.6,131.1,129.4,128.9,128.6,128.5,128.2,127.4,127.2,126.8,122.2,122.0,120.5,120.2,117.7,69.7,63.2,62.0,16.7.ir(thinfilm)3352,3023,2926,1705,1582,1485,1058,762,688cm-1；hrms(esi)m/zcalcdforc25h22no2[m+h]+:368.1651,found:368.1640.
2ab：固体,58mg,75％yield；mp59–60℃.1hnmr(400mhz,cdcl3):δ9.50(s,1h),7.23(d,j＝8.4hz,2h),7.12(d,j＝7.6hz,1h),7.07–7.03(m,3h),6.89(d,j＝7.6hz,1h),6.82–6.73(m,5h),6.63(d,j＝8.0hz,1h),6.27(d,j＝15.6hz,1h),4.66(d,j＝12.4hz,1h),4.29(brs,1h),4.26(d,j＝12.8hz,1h),3.72(s,3h).13cnmr(100mhz,cdcl3):δ197.0,159.7,154.3,149.9,132.2,130.1,128.9,128.5,128.0,127.5,127.1,126.9,124.6,122.7,122.1,120.3,117.6,114.0,110.7,70.0,63.0,61.6,55.3.ir(thinfilm)3360,3032,2924,1709,1606,1257,809,753cm-1；hrms(esi)m/zcalcdforc25h22no3[m+h]+:384.1600,found:384.1586.
2ac：固体,32mg,43％yield；mp38–39℃.1hnmr(400mhz,cdcl3):δ9.51(s,1h),7.20(d,j＝7.2hz,2h),7.12–7.04(m,6h),6.90(t,j＝7.2hz,2h),6.77–6.75(m,2h),6.65(d,j＝8.0hz,1h),6.36(d,j＝16.0hz,1h),4.74(brs,1h),4.67(d,j＝12.0hz,1h),4.30(d,j＝12.4hz,1h),2.26(s,3h).13cnmr(100mhz,cdcl3):δ197.0,154.2,149.7,138.2,133.0,132.6,130.1,129.3,128.9,128.1,127.5,127.0,126.7,124.7,122.7,122.1,120.3,117.6,110.8,70.0,63.0,61.6,21.1.ir(thinfilm)3371,3001,2924,1708,1607,1483,1261,1100,803cm-1；hrms(esi)m/zcalcdforc25h22no2[m+h]+:368.1651,found:368.1636.
2ad：固体,35mg,47％yield；mp132–133℃.1hnmr(400mhz,cdcl3):δ9.50(s,1h),7.23(d,j＝7.2hz,2h),7.12–7.04(m,6h),6.90(t,j＝7.2hz,2h),6.75–6.70(m,2h),6.65(d,j＝8.0hz,1h),6.36(d,j＝16.0hz,1h),4.73(brs,1h),4.65(d,j＝12.0hz,1h),4.33(d,j＝12.4hz,1h).13cnmr(100mhz,cdcl3):δ197.1,153.2,149.1,138.2,133.0,132.4,130.1,129.1,128.8,128.0,127.4,127.0,125.7,124.5,122.4,122.0,120.3,117.3,110.8,70.3,63.1,61.6.ir(thinfilm)3369,3004,2925,1706,1605,1481,1260,1106,801cm-1；hrms(esi)m/zcalcdforc24h19no2[m+h]+:372.1400,found:372.1387.
2ae：固体,48mg,57％yield；mp128–129℃.1hnmr(400mhz,cdcl3):δ9.65(s,1h),7.25(d,j＝7.6hz,2h),7.12–7.07(m,2h),7.00(t,j＝8.0hz,3h),6.85–6.80(m,3h),6.71–6.66(m,2h),6.53(d,j＝8.0hz,1h),6.46(d,j＝15.8hz,1h),4.59(d,j＝12.0hz,1h),4.49(d,j＝12.0hz,1h),4.45(brs,1h).13cnmr(100mhz,cdcl3):δ196.1,155.2,153.5,134.4,133.2,128.9,128.7,128.4,128.2,128.1,128.0,127.9,126.7,126.0,123.1,122.3,122.1,122.0,117.8,110.0,70.1,62.5,61.1.ir(thinfilm)3365,2924,2846,1705,1603,1480,1262,1105,794cm-1；hrms(esi)m/zcalcdforc25h19f3no2[m+h]+:422.1368,found:422.1347.
2af：固体,48mg,62％yield；mp67–68℃.1hnmr(400mhz,cdcl3):δ9.50(s,1h),7.17(d,j＝9.2hz,1h),7.10–7.04(m,3h),6.90–6.81(m,3h),6.84(d,j＝9.2hz,2h),6.77–6.75(m,3h),6.64(d,j＝8.0hz,1h),6.40(d,j＝15.6hz,1h),4.67(d,j＝12.4hz,1h),4.30(brs,1h),4.27(d,j＝12.4hz,1h),3.71(s,1h).13cnmr(100mhz,cdcl3):δ196.9,159.8,154.2,149.8,143.3,137.1,132.6,130.1,129.6,129.4,129.0,127.4,124.6,122.6,122.2,120.4,119.4,117.7,113.9,112.0,110.8,69.9,63.0,61.6,55.2.ir(thinfilm)3364,3002,2931,1705,1600,1481,1263,1105,796cm-1；hrms(esi)m/zcalcdforc25h22no3[m+h]+:384.1600,found:384.1605.
2ag：固体,56mg,65％yield；mp56–57℃.1hnmr(400mhz,cdcl3):δ9.49(s,1h),7.44(s,1h),7.31(d,j＝7.6hz,1h),7.21–7.18(m,2h),7.12–7.05(m,4h),6.91(t,j＝7.2hz,1h),6.85(d,j＝16.0hz,1h),6.79–6.75(m,2h),6.65(d,j＝7.6hz,1h),6.41(d,j＝15.6hz,1h),4.67(d,j＝12.4hz,1h),4.35(brs,1h),4.30(d,j＝12.8hz,1h).13cnmr(100mhz,cdcl3):δ196.9,154.2,149.7,137.9,131.2,131.0,130.8,130.2,130.1,129.6,129.1,127.3,126.5,125.4,124.7122.8,122.6,122.2,120.5,117.8,110.9,69.8,63.0,61.7.ir(thinfilm)3368,2925,2854,1709,1606,1483,1261,1022,752cm-1；hrms(esi)m/zcalcdforc24h19brno2[m+h]+:432.0599,found:432.0583.
2ah：固体,52mg,60％yield；mp54–55℃.1hnmr(400mhz,cdcl3):δ9.46(s,1h),7.49(d,j＝7.6hz,1h),7.34(d,j＝7.6hz,1h),7.28(d,j＝15.6hz,1h),7.18–7.13(m,2h),7.09–7.02(m,4h),6.92–6.89(m,1h),6.79(t,j＝7.6hz,2h),6.67(d,j＝8.0hz,1h),6.29(d,j＝16.0hz,1h),4.69(d,j＝12.4hz,1h),4.35(brs,1h),4.31(d,j＝12.4hz,1h).13cnmr(100mhz,cdcl3):δ197.1,154.2,149.9,136.2,132.8,132.2,131.8,130.2,129.4,129.1,127.5,127.4,127.3,126.6,124.6,123.9,122.6,122.2,120.4,117.7,110.9,69.9,63.0,61.5.ir(thinfilm)3360,2923,2852,1703,1609,1465,1259,741cm-1；hrms(esi)m/zcalcdforc24h19brno2[m+h]+:432.0599,found:432.0583.
2ai：固体,38mg,55％yield；mp59–60℃.1hnmr(400mhz,cdcl3):δ9.50(s,1h),7.27–7.24(m,1h),7.11–7.04(m,4h),6.90–6.86(m,1h),6.78–6.74(m,2h),6.69–6.61(m,2h),6.37(d,j＝15.6hz,1h),6.31–6.28(m,1h),6.21(m,1h),4.65(d,j＝12.4hz,1h),4.28(brs,1h),4.25(d,j＝12.4hz,1h).13cnmr(100mhz,cdcl3):δ196.8,154.3,151.5,149.8,142.5,130.1,129.0,127.6,127.4,126.7,124.7,122.7,122.1,121.0,120.4,117.6,111.4,110.8,109.5,69.8,63.0,61.7.ir(thinfilm)3364,2924,2853,1714,1604,1261,1016,752cm-1；hrms(esi)m/zcalcdforc22h18no3[m+h]+:344.1287,found:344.1275.
2aj：固体,24mg,46％yield；mp123–124℃.1hnmr(400mhz,cdcl3):δ9.65(s,1h),7.26(d,j＝7.2hz,1h),7.08–7.02(m,3h),6.93(d,j＝7.2hz,1h),6.76(dd,j＝13.6hz,7.6hz,2h),6.58(d,j＝7.6hz,1h),4.49(d,j＝12.4hz,1h),4.30(brs,1h),4.26(d,j＝12.4hz,1h).13cnmr(100mhz,cdcl3):δ198.7,153.5,149.8,129.9,129.4,128.7,125.6,124.8,123.4,121.9,120.0,117.5,110.7,65.5,62.7,60.9,24.5.ir(thinfilm)3365,3072,2952,1707,1606,1251,1094,804cm-1；hrms(esi)m/zcalcdforc17h16no2[m+h]+:266.1181,found:266.1208.
2ak：固体,25mg,44％yield；mp138–139℃.1hnmr(400mhz,cdcl3):δ7.25(d,j＝7.6hz,1h),7.05–6.98(m,3h),6.89(t,j＝7.2hz,1h),6.76–6.72(m,1h),6.65(d,j＝8.0hz,1h),6.53(d,j＝7.6hz,1h),4.53(d,j＝12.4hz,1h),4.26(d,j＝12.8hz,1h),4.23(brs,1h),2.00(s,3h),1.60(s,3h).13cnmr(100mhz,cdcl3):δ209.1,153.7,150.1,130.0,129.3,128.3,127.2,125.7,123.9,121.7,120.1,117.3,110.9,66.1,64.1,62.7,28.7,24.3.ir(thinfilm)3434,3013,2925,1697,1607,1464,1093,755,630cm-1；hrms(esi)m/zcalcdforc18h18no2[m+h]+:280.1338,found:280.1325.
2al：固体,57mg,66％yield；mp208–209℃.1hnmr(400mhz,cdcl3):δ7.24–7.08(m,9h),7.06(dd,j＝17.6hz,8.0hz,5h),6.87–6.83(m,1h),6.77–6.72(m,2h),6.60–6.56(m,2h),6.31(d,j＝16.0hz,1h),4.72(d,j＝12.0hz,1h),4.60(d,j＝12.0hz,1h),4.07(brs,1h).13cnmr(100mhz,cdcl3):δ201.9,154.7,150.5,139.7,136.1,131.5,131.4,129.7,129.0,128.6,128.5,128.4,127.9,127.8,127.5,127.4,126.8,126.6,124.6,122.1,120.4,117.7,111.1,70.9,67.1,64.6.ir(thinfilm)3329,2924,2852,1651,1484,1238,744cm-1；hrms(esi)m/zcalcdforc30h24no2[m+h]+:430.1807,found:430.1803.
2am：固体,39mg,52％yield；mp110–111℃.1hnmr(400mhz,cdcl3):δ9.50(s,1h),7.31–7.18(m,5h),7.10(dd,j＝18.4hz,7.6hz,2h),6.91(d,j＝16.0hz,1h),6.81–6.71(m,4h),6.67(d,j＝7.6hz,1h),6.37(d,j＝15.6hz,1h),4.66(d,j＝12.4hz,1h),4.28(brs,1h),4.25(d,j＝12.0hz,1h).13cnmr(100mhz,cdcl3):δ196.7,158.9(d,j＝239.1hz),150.4,149.6,135.5,133.1,130.2,128.8,128.7,128.4,128.1(d,j＝5.8hz),126.8,124.6,122.4,120.5,119.1(d,j＝8hz),116.4(d,j＝23.3hz),113.2(d,j＝23.3hz),110.8,70.0,63.3,61.4.ir(thinfilm)3363,2936,2867,1704,1602,1481,1267,1083,797cm-1；hrms(esi)m/zcalcdforc24h19fno2[m+h]+:372.1400,found:372.1395.
2an：固体,26mg,38％yield；mp59–60℃.1hnmr(400mhz,cdcl3):δ9.61(s,1h),7.11–7.01(m,4h),6.77–6.73(m,1h),6.58(d,j＝8.0hz,1h),4.50(d,j＝12.4hz,1h),4.25(brs,1h),4.21(d,j＝12.4,1h),1.67(s,3h).13cnmr(100mhz,cdcl3):δ198.2,154.4,149.6,130.1,127.9,127.0,125.1,124.8,123.1,121.6,120.6,120.3,110.7,65.4,62.8,60.7,24.3.ir(thinfilm)3350,2925,1709,1597,1261,1034,832cm-1；hrms(esi)m/zcalcdforc17h15brno2[m+h]+:344.0286,found:344.0274.
2ao：固体,28mg,48％yield；mp187–188℃.1hnmr(400mhz,cdcl3):δ9.64(s,1h),7.08–7.01(m,2h),6.96(s,1h),6.75–6.71(m,1h),6.58(d,j＝8.0hz,1h),6.50(s,1h),4.46(d,j＝12.4hz,1h),4.26(brs,1h),4.21(d,j＝12.0,1h),2.12(s,3h),2.07(s,3h),1.67(s,3h).13cnmr(100mhz,cdcl3):δ198.9,151.4,149.9,137.5,130.1,129.8,126.1,125.7,124.8,123.7,120.0,118.1,110.7,65.4,62.8,61.1,24.6,19.4,19.1.ir(thinfilm)3368,3021,2924,1717,1604,1463,1261,1094,803cm-1；hrms(esi)m/zcalcdforc19h20no2[m+h]+:294.1494,found:294.1475.
2ap：固体,26mg,51％yield；mp100–101℃.1hnmr(400mhz,cdcl3):δ9.62(s,1h),7.25(d,j＝7.2hz,1h),7.09–7.03(m,3h),6.95(d,j＝7.2hz,1h),6.78(dd,j＝13.2hz,7.2hz,2h),6.50(d,j＝7.6hz,1h),4.49(d,j＝12.4hz,1h),4.30(brs,1h),4.26(d,j＝12.4hz,1h),4.01(s,1h).13cnmr(100mhz,cdcl3):δ198.5,152.3,148.8,129.3,129.4,128.5,125.4,124.7,123.1,121.2,120.1,117.5,110.4,65.2,62.7,60.5.ir(thinfilm)3363,2951,2829,1708,1605,1250,1084,802cm-1；hrms(esi)m/zcalcdforc16h14no2[m+h]+:252.1025,found:252.1006.
2aq：固体,25mg,50％yield；mp103–104℃.1hnmr(400mhz,cdcl3):δ9.62(s,1h),7.24(d,j＝7.2hz,1h),7.08–7.02(m,2h),6.92(d,j＝7.2hz,2h),6.75(dd,j＝13.6hz,7.6hz,2h),6.53(d,j＝7.6hz,1h),4.45(d,j＝12.4hz,1h),4.33(brs,2h),4.26(d,j＝12.4hz,1h),4.10(s,1h).13cnmr(100mhz,cdcl3):δ198.3,153.4,149.8,129.3,129.2,128.5,125.6,124.6,123.1,121.7,121.0,117.0,110.7,65.4,62.7,60.6.ir(thinfilm)3360,2959,2826,1706,1604,1240,1054,801cm-1；hrms(esi)m/zcalcdforc16h15no2[m+h]+:251.1184,found:251.1172.
2ar：固体,23mg,43％yield；mp123–124℃.1hnmr(400mhz,cdcl3):δ9.61(s,1h),7.27(d,j＝7.4hz,1h),7.07–7.03(m,3h),6.92(d,j＝7.2hz,1h),6.74(dd,j＝13.6hz,7.6hz,2h),6.50(d,j＝7.6hz,1h),4.32(brs,1h),4.17(s,1h),3.91–3.84(m,2h),2.46–2.37(m,2h).13cnmr(100mhz,cdcl3):δ197.9,153.2,149.7,129.7,129.4,128.0,125.8,124.7,123.4,121.9,120.6,117.1,110.0,65.4,62.7,60.8,30.6.ir(thinfilm)3360,3014,2950,2822,1705,1603,1254,1074,793cm-1；hrms(esi)m/zcalcdforc17h16no2[m+h]+:266.1181,found:266.1172.
2as：固体,22mg,39％yield；mp133–134℃.1hnmr(400mhz,cdcl3):δ9.65(s,1h),7.27(d,j＝7.2hz,1h),7.04–7.01(m,2h),6.91(d,j＝7.2hz,2h),6.73(dd,j＝13.6hz,7.6hz,2h),6.54(d,j＝7.6hz,1h),4.31(brs,1h),4.16(s,1h),3.90–3.81(m,2h),2.43–2.35(m,2h),2.00–1.89(m,2h).13cnmr(100mhz,cdcl3):δ197.8,153.2,149.2,129.8,129.4,128.7,125.7,124.0,123.4,121.8,120.6,117.0,110.2,65.6,62.4,60.1,30.6,28.5.ir(thinfilm)3361,3021,2941,2824,1706,1602,1250,1074,797cm-1；hrms(esi)m/zcalcdforc18h18no2[m+h]+:280.1338,found:280.1324.
实施例2
按下述合成路线合成本发明所述的2,3-稠环吲哚啉衍生物。
2ba:r1＝4-br,r2＝phch＝ch,r3＝4-br,r4＝h,n＝1；
2bb:r1＝4-br,r2＝phch＝ch,r3＝3-br,r4＝h,n＝1；
2bc:r1＝4-br,r2＝(3-br)c6h4ch＝ch,r3＝4-cl,r4＝h,n＝1；
2bd:r1＝4-br,r2＝(4-me)c6h4ch＝ch,r3＝4-cl,r4＝me,n＝1；
2be:r1＝3-cl,r2＝me,r3＝4-me,r4＝h,n＝1；
2bf:r1＝4-br,r2＝me,r3＝4-me,r4＝4-clc6h4,n＝1；
2bg:r1＝3-cl,r2＝me,r3＝4-me,r4＝me,n＝1；
2bh:r1＝4-br,r2＝h,r3＝4-br,r4＝h,n＝1；
2bi:r1＝4-br,r2＝h,r3＝3-cl,r4＝me,n＝2；
2bj:r1＝4-br,r2＝me,r3＝4-br,r4＝me,n＝1,x＝n。
取n-芳基α,β-不饱和硝酮底物1(0.2mmol)置于反应管中，加入2ml有机溶剂(其中目标物2ba-2bd采用的有机溶剂分别为丙酮、三氯甲烷、正己烷和二氧六环，目标物2be-2bj采用的有机溶剂均为四氯化碳)，在25℃下搅拌反应10-36h，所得反应物减压除去溶剂，残渣上硅胶柱层析分离(石油醚/乙酸乙酯＝50：1～10：1，体积比)，得到目标产物2。不同的目标产物及其表征如下：
2ba:固体,64mg,63％yield；mp89–90℃.1hnmr(400mhz,cdcl3):δ9.45(s,1h),7.49(d,j＝7.6hz,1h),7.34(d,j＝7.6hz,1h),7.28(d,j＝15.6hz,1h),7.18–7.13(m,2h),7.09–7.02(m,3h),6.92(s,1h),6.79(t,j＝7.6hz,2h),6.67(d,j＝8.0hz,1h),6.29(d,j＝16.0hz,1h),4.69(d,j＝12.4hz,1h),4.35(brs,1h),4.31(d,j＝12.4hz,1h).13cnmr(100mhz,cdcl3):δ197.0,153.2,149.8,136.1,132.7,132.1,131.7,130.0,129.2,129.1,127.6,127.3,126.4,124.5,122.4,122.2,120.3,117.6,110.8,69.8,63.1,61.4.ir(thinfilm)3361,2920,2851,1703,1600,1461,1259,740cm-1；hrms(esi)m/zcalcdforc24h18br2no2[m+h]+:509.9704,found:509.9702.
2bb:固体,63mg,61％yield；mp93–94℃.1hnmr(400mhz,cdcl3):δ9.46(s,1h),7.48(d,j＝7.6hz,1h),7.35(d,j＝7.6hz,1h),7.29(d,j＝15.6hz,1h),7.18–7.15(m,2h),7.08–7.01(m,3h),6.90(s,1h),6.80(t,j＝7.6hz,2h),6.65(d,j＝8.0hz,1h),6.30(d,j＝16.0hz,1h),4.68(d,j＝12.4hz,1h),4.34(brs,1h),4.30(d,j＝12.4hz,1h).13cnmr(100mhz,cdcl3):δ197.1,154.2,149.7,136.3,132.6,132.2,131.7,129.4,129.0,127.5,127.4,126.3,124.4,123.3,122.5,122.3,120.3,117.6,110.7,69.6,63.0,61.3.ir(thinfilm)3359,2922,2854,1702,1604,1460,1258,741cm-1；hrms(esi)m/zcalcdforc24h18br2no2[m+h]+:509.9704,found:509.9711.
2bc:固体,50mg,46％yield；mp95–96℃.1hnmr(400mhz,cdcl3):δ9.46(s,1h),7.49(d,j＝7.6hz,1h),7.36(d,j＝7.6hz,1h),7.29(d,j＝15.6hz,1h),7.18–7.16(m,2h),7.08–7.03(m,2h),6.93(s,1h),6.82(t,j＝7.6hz,2h),6.64(d,j＝8.0hz,1h),6.31(d,j＝16.0hz,1h),4.67(d,j＝12.4hz,1h),4.33(brs,1h),4.31(d,j＝12.4hz,1h).13cnmr(100mhz,cdcl3):δ197.2,154.2,149.4,136.3,132.5,132.4,131.6,130.0,129.4,129.1,127.3,127.2,127.0,126.3,125.4,122.9,122.6,122.2,120.1,117.5,110.7,69.5,63.1,61.3.ir(thinfilm)3359,2923,2853,1700,1603,1462,1257,742cm-1；hrms(esi)m/zcalcdforc24h17br2clno2[m+h]+:543.9315,found:543.9327.
2bd:固体,45mg,45％yield；mp80–81℃.1hnmr(400mhz,cdcl3):δ7.49(d,j＝7.6hz,1h),7.35(d,j＝7.6hz,1h),7.28(d,j＝15.6hz,1h),7.19–7.16(m,2h),7.07–7.03(m,2h),6.95(s,1h),6.84(t,j＝7.6hz,2h),6.67(d,j＝8.0hz,1h),6.30(d,j＝16.0hz,1h),4.66(d,j＝12.4hz,1h),4.35(brs,1h),4.30(d,j＝12.4hz,1h),2.32(s,3h),2.14(s,3h).13cnmr(100mhz,cdcl3):δ197.1,153.2,148.4,137.3,132.6,132.3,131.5,130.1,129.2,129.0,128.1,127.5,127.0,126.2,125.4,123.1,122.8,122.5,121.4,117.4,110.3,69.4,63.0,61.2,27.5,21.3.ir(thinfilm)3362,2922,2851,1705,1601,1460,1256,743cm-1；hrms(esi)m/zcalcdforc26h22brclno2[m+h]+:494.0522,found:494.0534.
2be:固体,40mg,56％yield；mp85–86℃.1hnmr(400mhz,cdcl3):δ9.64(s,1h),7.08–7.01(m,2h),6.96(s,1h),6.75–6.71(m,1h),6.58(d,j＝8.0hz,1h),6.50(s,1h),4.46(d,j＝12.4hz,1h),4.26(brs,1h),4.21(d,j＝12.0,1h),2.07(s,3h),1.67(s,3h).13cnmr(100mhz,cdcl3):δ198.9,151.4,149.9,137.5,130.1,129.8,126.1,125.7,124.8,123.7,120.0,118.1,110.7,65.4,62.8,61.1,24.6,19.1.ir(thinfilm)3368,3021,2924,1717,1604,1463,1261,1094,803cm-1；hrms(esi)m/zcalcdforc18h17no2[m+h]+:358.0443,found:358.0421.
2bf:固体,47mg,51％yield；mp110–111℃.1hnmr(400mhz,cdcl3):δ7.07–7.02(m,3h),6.95(s,1h),6.74–6.71(m,3h),6.78(d,j＝8.0hz,1h),6.57(d,j＝8.0hz,1h),6.51(s,1h),4.44(d,j＝12.4hz,1h),4.25(brs,1h),4.20(d,j＝12.0,1h),2.02(s,3h),1.65(s,3h).13cnmr(100mhz,cdcl3):δ200.1,151.4,149.9,137.5,136.2,134.2,132.6,130.1,129.8,126.1,125.7,124.8,123.7,122.6,120.0,118.1,110.7,65.4,62.8,61.1,24.6,19.1.ir(thinfilm)3363,3020,2922,1715,1600,1461,1262,1093,801cm-1；hrms(esi)m/zcalcdforc24h20brclno2[m+h]+:468.0366,found:468.0352.
2bg:固体,39mg,60％yield；mp117–118℃.1hnmr(400mhz,cdcl3):δ7.09–7.00(m,2h),6.97(s,1h),6.75–6.71(m,1h),6.59(d,j＝8.0hz,1h),6.52(s,1h),4.45(d,j＝12.4hz,1h),4.27(brs,1h),4.20(d,j＝12.0,1h),2.13(s,3h),2.07(s,3h),1.66(s,3h).13cnmr(100mhz,cdcl3):δ206.1,151.3,149.8,137.4,132.1,129.7,128.1,125.3,124.2,123.5,120.1,118.0,110.2,65.1,62.6,61.0,24.6,24.4,19.1.ir(thinfilm)3366,3020,2923,1714,1600,1461,1260,1092,802cm-1；hrms(esi)m/zcalcdforc19h19clno2[m+h]+:328.1104,found:328.1123.
2bh:固体,50mg,62％yield；mp120–121℃.1hnmr(400mhz,cdcl3):δ9.62(s,1h),7.23(d,j＝7.2hz,1h),7.07–7.02(m,2h),6.96(d,j＝7.2hz,1h),6.76(d,j＝7.2hz,1h),6.52(d,j＝7.6hz,1h),4.49(d,j＝12.4hz,1h),4.31(brs,1h),4.25(d,j＝12.4hz,1h),4.00(s,1h).13cnmr(100mhz,cdcl3):δ198.9,152.1,148.7,129.7,129.2,128.7,125.5,124.6,123.0,121.3,120.0,117.4,110.3,65.1,62.8,60.4.ir(thinfilm)3360,2952,2828,1706,1604,1251,1083,800cm-1；hrms(esi)m/zcalcdforc16h12brno2[m+h]+:407.9235,found:407.9221.
2bi:固体,40mg,51％yield；mp120–121℃.1hnmr(400mhz,cdcl3):δ7.25(d,j＝7.4hz,1h),7.07–7.02(m,1h),6.91(d,j＝7.2hz,1h),6.72(d,j＝7.6hz,2h),6.53(d,j＝7.6hz,1h),4.33(brs,1h),4.15(s,1h),3.92–3.81(m,2h),2.45–2.39(m,2h).13cnmr(100mhz,cdcl3):δ197.8,153.0,149.5,129.6,129.3,128.1,125.3,124.8,123.2,121.0,120.7,117.3,110.1,65.3,63.7,60.2,30.5.ir(thinfilm)3359,3015,2952,2821,1704,1602,1250,1071,792cm-1；hrms(esi)m/zcalcdforc18h16brclno2[m+h]+:392.0053,found:392.0042.
2bj:固体,51mg,57％yield；mp121–122℃.1hnmr(400mhz,cdcl3):δ7.09–7.03(m,2h),6.95(s,1h),6.74–6.71(m,1h),6.57(d,j＝8.0hz,1h),6.52(s,1h),4.43(d,j＝12.4hz,1h),4.26(brs,1h),4.21(d,j＝12.0,1h),2.12(s,3h),2.04(s,3h),1.65(s,3h).13cnmr(100mhz,cdcl3):δ206.2,151.1,149.5,137.3,132.0,129.4,128.9,125.2,124.1,123.2,120.0,118.2,110.1,65.0,62.7,61.9,24.3,24.1,19.9.ir(thinfilm)3368,3021,2920,1716,1605,1462,1263,1094,801cm-1；hrms(esi)m/zcalcdforc19h19br2n2o[m+h]+:448.9864,found:448.9862.
实验例1：本发明所述2,3-稠环吲哚啉衍生物对多种人肿瘤株进行体外抑制活性实验：
(1)细胞培养：将mgc-803、hepg-2、nci-h460、skov3、t24、7702细胞培养于含10％(体积比)胎牛血清和1％(体积比)双抗(含青霉素和链霉素)的dmem培养基，在温度37℃、5％co2及95％空气的培养箱中培养，隔天换液。待细胞长满后进行传代，冻存。
(2)种板：取处于对数生长期的细胞，去掉旧培养基，用pbs洗涤两次，胰蛋白酶消化细胞，待细胞变圆后加入新的培养基终止细胞消化并吹打悬浮细胞，制成单个细胞悬液。取适量的细胞悬液，加入一定量的培养基稀释，接种到96孔板中，每孔180μl，每孔细胞数为20000-40000。
(3)加药：于种有肿瘤细胞的96孔板中加入待测样品，每孔20μl，使样品的最终浓度为10μm，进行初筛。根据初筛的结果，对化合物设置不同的浓度梯度进行筛选，每组设置5个复孔。加化合物后放co2培养箱培养48h，每孔加入10μl配好的mtt溶液，放co2培养箱继续培养4～6h。
(4)测试：吸弃96孔板内的培养基，加入100μl的dmso，放摇床上震荡5～10min，使结晶的甲瓒完全溶解。用酶标仪以570nm的吸收波长，630nm的参比波长双波长测定吸光度(od)值，计算抑制率。抑制率＝(1-样品组od值/空白组od值)×100％，用spss软件分别计算各化合物对不同肿瘤细胞株的ic50值。其测试结果如下表1所示：
表1：