CN114736149B - 一种2,3-二氢色胺类化合物的合成方法 - Google Patents
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Abstract
本发明提供一种2,3‑二氢色胺类化合物的合成方法，以exo选择的N‑烯丙基苯胺的氨烷基化/环化级联反应制备得到2,3‑二氢色胺类化合物。本发明是首例从非环原料出发的2,3‑二氢色胺衍生物合成方法，也是涉及非活化烯烃的简单酰胺α‑C(sp3)−H键官能团化反应的罕见例子。本发明反应在混合水相中进行，并且底物范围广、条件简单、成本低。
Description
相关申请
本申请是2019年03月08日提交的中国专利申请201910178150.4的分案申请，所述申请的公开内容均援引加入本文。
技术领域
本发明具体涉及一种2,3-二氢色胺类化合物的合成方法，属于有机合成技术领域。
背景技术
色胺是构建天然产物和药物的重要骨架结构，通过色胺系列衍生物能合成多种具有生物活性的化学物质，如用于治疗多发性骨髓瘤的帕比司他，用于治疗偏头痛的那拉曲坦、舒马曲坦、利扎曲普坦、依来曲普坦、阿莫曲坦、唑吗曲坦等。广泛存在于生物碱和临床药物分子中的2,3-二氢色胺衍生物是新药设计的重要先导化合物(文献1：D.M. Krüger,A.Glas,D.Bier,N.Pospiech,K.Wallraven,L.Dietrich,C.Ottmann,O.Koch,S. Hennigand T.N.Grossmann,J.Med.Chem.,2017,60,8982-8988；文献2：D.DeCarlo andM.K.Hadden,Eur.J.Med.Chem.,2012,56,179-194)，现有技术中通常通过母体色胺的衍生化反应得到2,3-二氢色胺(文献3：Y.J.Diaz,Z.A.Page,A.S.Knight,N.J.Treat,J.R.Hemmer,C.J.Hawker and J.R.de Alaniz,Chem.Eur.J.,2017,23,3562–3566；文献4：A.Kulkarni,W.Zhou and B.
Org.Lett.,2011,13,5124–5127)，但是含取代基的母体色胺底物来源狭窄，难以大规模应用。此外，通过母体色胺衍生化反应通常需要高温高压的苛刻条件，而且还需要依赖Bronsted或Lewis酸催化剂，以及过渡金属催化剂，会导致过渡金属在产物中的残留难以除去，从而限制了工业应用。
发明内容
为了解决现有技术中的问题，本发明的目的在于提供一种2,3-二氢色胺类化合物的合成方法，该方法底物选择范围广、工艺条件简单、生产成本低，适合大规模应用。
本发明的目的是这样实现的：
一种2,3-二氢色胺类化合物(式II化合物)的合成方法，其特征在于，反应路线如下：
其中：
R1是氢或C1-6烷基；
R2是氢、卤素、C1-6烷基或苯基；
R3是COR7或或SO2R8；
R4是氢或C1-6烷基；
R5是氢或C1-6烷基；
R6是氢或C1-6烷基；
R7是C1-17烷基或-O-C1-6烷基；
R8是C1-6烷基。
本发明所述“卤素”是指氟、氯、溴或碘，优选为氟、氯或溴。本发明所述“C1-6烷基”是指具有1-6个碳原子的饱和的直链或支链烃基，例如甲基、乙基、丙基、异丙基、正丁基、异丁基、仲丁基、叔丁基、正戊基、异戊基、新戊基、正己基、异己基等，优选甲基、乙基、丙基、异丙基、叔丁基或异丁基。本发明所述“C1-17烷基”是指具有1-17 个碳原子的饱和的直链或支链烃基，例如甲基、乙基、丙基、异丙基、正丁基、异丁基、仲丁基、叔丁基、正戊基、异戊基、新戊基、正己基、异己基、n-C7H15、n-C9H19、n-C11H23、 n-C17H35等。本发明所述“-O-C1-6烷基”，是指具有1-6个碳原子的饱和的直链或支链烷氧基，例如甲氧基、乙氧基、叔丁氧基等。
本发明的一个实施方案中，所述催化剂DCP的用量为2-3当量。本发明的一个实施方案中，本发明使用的溶剂为酰胺与水形成的混合水相溶剂，其中酰胺与水的体积比为3～5:1。本发明的反应温度为120±5℃(115℃～125℃)。
本发明的一个实施方案中，本发明中R1选自氢或甲基；R2选自氢、甲基、氯、溴或苯基；R3是COR7；R4是氢、甲基或乙基；R5选自氢、甲基或乙基；R6选自氢、甲基或乙基；R7选自甲基、乙基、叔丁基、n-C7H15、n-C9H19、n-C11H23或n-C17H35。
本发明的一个实施方案包括其中R2是苯基的化合物(如式I)，所述苯基是未取代的或被一个或多个下列基团取代：氢、甲基、氯、溴或苯基；式I化合物中，R1可以独立的为邻位、间位或对位，可以邻位、间位或/和对位同时取代，也可以单独取代。
本发明式II化合物选自2a-2k化合物，具体如下表1。
表1 2a-2n化合物
| 编号 | 化合物名称 |
| 2a1 | N-(2-(1-乙酰基-3-甲基吲哚啉-3-基)乙基)-N-甲基乙酰胺 |
| 2a2 | N-(2-(1-乙酰基-3,5-二甲基吲哚啉-3-基)乙基)-N-甲基乙酰胺 |
| 2a3 | N-(2-(1-乙酰基-5-溴-3-甲基吲哚啉-3-基)乙基)-N-甲基乙酰胺 |
| 2a4 | N-(2-(1-乙酰基-5-氯-3-甲基吲哚啉-3-基)乙基)-N-甲基乙酰胺 |
| 2a5 | N-(2-(1-乙酰基-3-甲基-5-苯基吲哚啉-3-基)乙基)-N-甲基乙酰胺 |
| 2b1 | N-(2-(3,5-二甲基-1-丙酰基吲哚啉-3-基)乙基)-N-甲基乙酰胺 |
| 2b2 | N-(2-(5-溴-3-甲基-1-丙酰基吲哚啉-3-基)乙基)-N-甲基乙酰胺 |
| 2b3 | N-(2-(5-氯-3-甲基-1-丙酰基吲哚啉-3-基)乙基)-N-甲基乙酰胺 |
| 2c1 | N-甲基-N-(2-(3-甲基-1-辛酰基吲哚啉-3-基)乙基)乙酰胺 |
| 2c2 | N-(2-(3,5-二甲基-1-辛酰基吲哚啉-3-基)乙基)-N-甲基乙酰胺 |
| 2c3 | N-(2-(5-溴-3-甲基-1-辛酰基吲哚啉-3-基)乙基)-N-甲基乙酰胺 |
| 2c4 | N-(2-(5-氯-3-甲基-1-辛酰基吲哚啉-3-基)乙基)-N-甲基乙酰胺 |
| 2d1 | N-(2-(1-癸酰基-3,5-二甲基吲哚啉-3-基)乙基)-N-甲基乙酰胺 |
| 2d2 | N-(2-(5-溴-1-癸酰基-3-甲基吲哚啉-3-基)乙基)-N-甲基乙酰胺 |
| 2e1 | N-(2-(1-十二酰基-3,5-二甲基吲哚啉-3-基)乙基)-N-甲基乙酰胺 |
| 2e2 | N-(2-(5-溴-1-十二酰基-3-甲基吲哚啉-3-基)乙基)-N-甲基乙酰胺 |
| 2f1 | N-(2-(3,5-二甲基-1-十八酰基-3-基)乙基)-N-甲基乙酰胺 |
| 2f2 | N-(2-(5-溴-3-甲基-1-十八酰基吲哚啉-3-基)乙基)-N-甲基乙酰基 |
| 2g | N-(2-(3,5-二甲基-1-新戊酰基吲哚啉-3-基)乙基)-N-甲基乙酰胺 |
| 2h1 | 5-氯-3-甲基-3-(2-(N-甲基乙酰胺基)乙基)吲哚啉-1-羧酸叔丁酯 |
| 2h2 | N-(2-(5-氯-1-(乙磺酰基)-3-甲基吲哚啉-3-基)乙基)-N-甲基乙酰胺 |
| 2j | N-(2-(1-乙酰基-4-氯-3-甲基吲哚啉-3-基)乙基)-N-甲基乙酰胺 |
| 2k | N-(2-(1-乙酰基-5-溴吲哚啉-3-基)乙基)-N-甲基乙酰胺 |
| 2l | N-(2-(3,5-二甲基-1-辛酰基吲哚啉-3-基)乙基)-N-甲基甲酰胺 |
| 2m | 5-((3,5-二甲基-1-辛酰基吲哚啉-3-基)甲基)-1-甲基吡咯烷-2-酮 |
| 2n | N-(2-(1-乙酰基-3-甲基吲哚啉-3-基)乙基)乙酰胺 |
有益效果
本发明提供一种合成2,3-二氢色胺类化合物的方法，以非活化烯烃N-烯丙基苯胺衍生物为原料，与酰胺发生exo选择的氨烷基化/环化级联反应，生成2,3-二氢色胺类化合物。本发明为首例从非环原料出发合成2,3-二氢色胺衍生物的方法，也是涉及非活化烯烃的简单酰胺α-C(sp3)-H键官能团化反应的罕见例子。本发明反应过程无金属催化剂参与，不用担心产物中过渡金属残留的问题，同时溶剂为原料酰胺与水形成的混合水相溶剂，反应过程不涉及其他有机溶剂，不仅大大降低了溶剂成本，还简化了后处理操作步骤，经济价值显著。
具体实施方式
为了使本发明的目的和技术方案更加清楚，下面对本发明的优选实施例进行详细的描述。要说明的是：以下实施例只用于对本发明进行进一步的说明，而不能理解为对本发明保护范围的限制。本领域的技术人员根据本发明的上述内容做出的一些非本质的改进和调整均属于本发明的保护范围。本发明原料式I化合物和酰胺可以市售购买，也可以参照文献(文献5：D.Liang,Q.Dong,P.Xu,Y.Dong,W.Li,Y.Ma,J.Org.Chem.2018, 83,11978-11986.；文献6:S.O'Sullivan,E.Doni,T.Tuttle,J.A.Murphy.Angew.Chem.Int. Ed.2014,53,474–478；Angew.Chem.2014,126,484–488；文献7:Z.Wu,S.Li,H.Xu.Angew.Chem.Int.Ed.2018,57,14070–14074；Angew.Chem.2018,130,14266–14270；文献 8：CN201811634880.2)制备得到。
实施例1
非活化烯烃烷基化合成2,3-二氢色胺(以2a1的合成为例)，反应路线如下：
操作步骤：氩气保护下，向装有磁力搅拌子的10mL Schlenk管中依次加入N-(2-甲基烯丙基)-N-苯基乙酰胺1a1(38mg，0.2mmol)，过氧化二异丙苯(DCP，162mg， 0.6mmol)，N,N-二甲基乙酰胺(DMA，1.0mL)和水(0.2mL)。该混合物在120℃反应6h，冷却后用饱和Na2S2O3(0.5mL)和水(5.0mL)淬灭，再用CH2Cl2(10.0mL) 萃取三次。合并有机相，蒸除有机溶剂。对残余物使用硅胶(300-400目)进行柱层析 (石油醚-丙酮＝6/1，v/v)，得到浅黄色油状物2a1(39mg，71％产率)。
参照上述实施例1，考察催化剂、溶剂、温度对反应的影响，具体情况见表2。
表2.催化剂、溶剂、温度对反应的影响a
a反应条件：1a1(0.2mmol)，溶剂(1.2mL)，Ar，6h。b加入Cu2O(10mol％)作为复合催化剂。c5.0-6.0mol/L的癸烷溶液。d加入10equiv的DMA。e v/v.
发明人从N-(2-甲基丙烯基)乙酰苯胺1a1和N,N-二甲基乙酰胺(DMA)的氨烷基化/环化级联反应开始本研究(表2)。在120℃的DMA溶剂中混合1a1与10mol％的Cu2O和3当量的过氧化二叔丁基(DTBP)，6h后得到36％产率的2,3-二氢色胺产物2a1(序号1)。铜催化剂不是必须的，去掉它时得到差不多的产率(序号2)。使用过氧化二异丙苯(DCP)作为引发反应的催化剂时，2,3-二氢色胺2a1的产率提高到 44％(序号3)，而使用过苯甲酸特丁酯(TBPB)时产率略有下降(序号4)。其它催化剂，如过氧化二苯甲酰(BPO)、过氧化叔丁醇(TBHP)、K2S2O8和Oxone，对该反应均无效(序号5)。使用10当量DMA在其它溶剂中进行该反应的尝试均没有成功 (序号6-8)。反应在1,2-二氯乙烷(DCE，序号6)或甲苯(序号7)中进行时，2,3-二氢色胺2a1的产率极低，而其他极性溶剂中的反应仅观察到痕迹量的2a1。这些被测试的极性溶剂包括四氢呋喃(THF)、CH3NO2、二甲基亚砜(DMSO)和乙醇(序号8)。令人惊讶的是，把溶剂更换为DMA/H2O(5:1，v/v)混合溶剂时，二氢色胺2a1的产率产率提高到71％(序号9)；然而进一步提高混合溶剂中水的比例会导致产率降低(序号10-12)。
参照上述实施例，在最优反应条件下，考察底物对本发明反应的影响，具体情况见下表3。
表3.从N-烯丙基苯胺合成2,3-二氢色胺a
实验结果显示，N-芳基对位有甲基、溴或氯原子的N-(2-甲基烯丙基)乙酰苯胺与DMA反应生成5-位取代2,3-二氢色胺2a2-4，产率68-76％，而5-苯基产物2a5的产率仅有中等。丙酰基、辛酰基、癸酰基和十二烷酰基等N-保护基(PG)也都被该反应兼容，对应2,3-二氢色胺产物2b-e从带有电中性、富电子或贫电子N-芳基的烯丙化酰胺合成得到，产率中等到高。使用特戊酰基作为N-保护基时，吲哚啉2g高产率生成。叔丁氧羰基和乙磺酰基也是可用的保护基，对应二氢色胺产物2h1,2分别以61％和44％的产率生成。带有3-氯取代基的烯丙化乙酰苯胺也是高活性底物，4-氯二氢色胺2j产率为43％。
根据鲍德温规则(Baldwin's rule)，6-endo-trig型环合可能是本反应的竞争反应。因此，为了避免该竞争过程，初期研究都以N-(2-甲基烯丙基)苯胺为底物。在以上所有反应中都实现了exo选择性之后，发明人尝试将反应拓展到没有甲基分支的普通N-烯丙基苯胺。令人高兴的是，对应5-exo-trig产物2k专一地生成，产率60％，仍然没有检测到endo产物。
发明人继续研究了酰胺溶剂的范围。当N,N-二甲基甲酰胺(DMF)/H2O混合液被用作溶剂时，目标2,3-二氢色胺2l以36％的产率生成。使用含水N-甲基吡咯烷酮(NMP) 作为底物时，对应氨烷基化吲哚啉产物2m高产率生成。令人欣喜的是，本氨烷基化/ 环化级联反应还可以被拓展到N-甲基乙酰胺溶剂。N-甲基乙酰胺带有一个未保护的酰胺N-H键，导致它过去在酰胺α-C(sp3)-H键官能团化反应不能被使用。该反应能生成中等产率的乙酰基保护的伯胺2n。因此，本发明呈现的是一个能同时合成二级和一级 2,3-二氢色胺的通用方法。
目标产物的核磁数据
2a1,N-(2-(1-乙酰基-3-甲基吲哚啉-3-基)乙基)-N-甲基乙酰胺，N-(CO)键旋转受阻产生 20:10:3:2四个不可分离的旋转异构体混合物(主要异构体和次要异构体分别用major和 minor表示，另外还有2个旋转异构体的含量较少，因而未予表征，仅表征major和minor 异构体)，浅黄色液体。1H NMR(400MHz,CDCl3)δ＝1.38(s,3H major),1.43(s,3Hminor),1.79-1.98(stack,2H major and 5H minor),2.02(s,3H major),2.24(s,3Hminor), 2.25(s,3H major),2.84(s,3H minor),2.87(s,3H major),2.95-3.04(stack,1Hmajor and 1H minor),3.16-3.24(m,1H minor),3.42-3.49(m,1H major),3.72(d,J＝10.4Hz,1H major), 3.78(d,J＝10.3Hz,1H minor),3.87(d,J＝10.4Hz,1H minor),4.11(d,J＝10.4Hz,1H major),7.03-7.13(stack,2H major and 2H minor),7.19-7.27(stack,1H major and 1H minor), 8.19(d,J＝8.1Hz,1H major),8.22(d,J＝8.1Hz,1Hminor)；13C{1H}NMR(100MHz, CDCl3)δ＝170.32(major),169.98(minor),168.82(major),168.50(minor),142.12(minor), 142.08(major),138.17(major),136.95(minor),128.50(minor),128.03(major),124.07 (minor),123.81(major),122.07(major),122.00(minor),117.18(minor),117.00(major), 61.11(minor),60.78(major),46.84(minor),44.11(major),42.53(major),42.30(minor), 39.82(minor),38.33(major),36.24(major),33.26(minor),27.19(major and minor),24.32 (major),24.29(minor),21.82(major),20.92(minor)；HRMS(ESI-TOF)Calcd for C16H23N2O2 +([M+H]+)275.1754.Found275.1762.
2a2,N-(2-(1-乙酰基-3,5-二甲基吲哚啉-3-基)乙基)-N-甲基乙酰胺，N-(CO)键旋转受阻产生26:13:4:3四个不可分离的旋转异构体混合物(主要异构体和次要异构体分别用major 和minor表示，另外还有2个旋转异构体的含量较少，因而未予表征，仅表征major和 minor异构体),浅黄色液体。1H NMR(400MHz,CDCl3)δ＝1.36(s,3H major),1.42(s, 3H minor),1.77-1.97(stack,2H major and 5H minor),2.02(s,3H major),2.22(s,3H minor), 2.23(s,3H major),2.32(s,3H major),2.33(s,3H minor),2.85(s,3Hminor),2.88(s,3H major),2.96-3.05(stack,1H major and 1H minor),3.16-3.24(m,1Hminor),3.42-3.49(m, 1H major),3.70(d,J＝10.4Hz,1H major),3.76(d,J＝10.4Hz,1Hminor),3.85(d,J＝10.4 Hz,1H minor),4.09(d,J＝10.4Hz,1H major),6.92(s,1Hmajor),7.01(d,J＝7.2Hz,1H major,and brs(stack),1H minor),7.05(d,J＝7.6Hz,1Hminor),8.05(d,J＝8.2Hz,1H major),8.08(d,J＝8.2Hz,1H minor)；13C{1H}NMR(100MHz,CDCl3)δ＝170.31(major), 169.98(minor),168.47(major),168.16(minor),139.86(minor),139.81(major),138.31 (major),137.11(minor),133.74(minor),133.38(major),128.97(minor),128.52(major), 122.64(major),122.53(minor),116.91(minor),116.73(major),61.24(minor),60.97 (major),46.87(minor),44.14(major),42.48(major),42.26(minor),39.82(minor),38.34 (major),36.26(major),33.26(minor),27.13(minor),27.09(major),24.20(major),24.17 (minor),21.82(major),21.14(major and minor),20.88(minor)；HRMS(ESI-TOF)Calcd for C17H25N2O2 +([M+H]+)289.1911.Found 289.1913.
2a3,N-(2-(1-acetyl-5-bromo-3-methylindolin-3-yl)ethyl)-N-methylacetamide,N-(2-(1-乙酰基-5-溴-3-甲基吲哚啉-3-基)乙基)-N-甲基乙酰胺,DMAN-(CO)键旋转受阻产生4:1不可分离的旋转异构体混合物(另外两个异构体由于酰基苯胺N-(CO)旋转受阻产生，获得量少未予表征),浅黄色液体。1H NMR(400MHz,CDCl3)δ＝1.37(s,3H major),1.43(s, 3H minor),1.78-1.91(stack,2H major and 2H minor),1.95(s,3Hminor),2.02(s,3H major), 2.23(s,3H minor),2.24(s,3H major),2.86(s,3H minor),2.90(s,3H major),2.93-3.07 (stack,1H major and 1H minor),3.18-3.26(m,1Hminor),3.42-3.49(m,1H major),3.72(d, J＝10.5Hz,1H major),3.79(d,J＝10.4Hz,1Hminor),3.87(d,J＝10.4Hz,1H minor), 4.16(d,J＝10.4Hz,1H major),7.21(d,J＝2.0Hz,1H major),7.22(d,J＝1.8Hz,1H minor),7.32(dd,J＝2.1,8.6Hz,1H major),7.36(dd,J＝2.0,8.6Hz,1H minor),8.08(d,J ＝8.6Hz,1H major),8.11(d,J＝8.6Hz,1Hminor)；13C{1H}NMR(100MHz,CDCl3)δ＝ 170.41(major),169.92(minor),168.93(major),168.54(minor),141.24(major),141.21 (minor),140.62(major),139.38(minor),131.44(minor),130.96(major),125.28(major and minor),118.71(minor),118.54(major),116.44(minor),116.12(major),61.18(minor), 60.78(major),46.72(minor),43.99(major),42.66(major),42.40(minor),39.65(minor), 38.35(major),36.33(major),33.31(minor),27.09(major),27.01(minor),24.22(major), 24.18(minor),21.81(major),20.96(minor)；HRMS(ESI-TOF)Calcd for C16H22BrN2O2 + ([M+H]+)353.0859.Found353.0858.
2a4,N-(2-(1-乙酰基-5-氯-3-甲基吲哚啉-3-基)乙基)-N-甲基乙酰胺,DMA N-(CO)键旋转受阻产生7:2不可分离的旋转异构体混合物(另外两个异构体由于酰基苯胺N-(CO)旋转受阻产生，获得量少未予表征)，浅黄色液体。1H NMR(400MHz,CDCl3)δ＝1.37(s,3Hmajor),1.43(s,3H minor),1.78-1.90(stack,2H major and 2H minor),1.95(s,3Hminor), 2.03(s,3H major),2.24(s,3H minor),2.25(s,3H major),2.86(s,3H minor),2.90(s,3H major),2.95-3.04(stack,1H major and 1H minor),3.18-3.26(m,1Hminor),3.42-3.50(m, 1H major),3.73(d,J＝10.4Hz,1H major),3.80(d,J＝10.4Hz,1Hminor),3.88(d,J＝10.4 Hz,1H minor),4.17(d,J＝10.4Hz,1H major),7.07(d,J＝2.1Hz,1H major),7.08(d,J＝ 2.2Hz,1H minor),7.17(dd,J＝2.2,8.6Hz,1H major),7.22(dd,J＝2.2,8.6Hz,1H minor), 8.13(d,J＝8.6Hz,1H major),8.16(d,J＝8.6Hz,1Hminor)；13C{1H}NMR(100MHz, CDCl3)δ＝170.42(major),169.93(minor),168.88(major),168.50(minor),140.73(major), 140.70(minor),140.21(major),138.99(minor),128.99(minor),128.62(major),128.50 (minor),128.03(major),122.37(major),122.34(minor),118.23(minor),118.04(major), 61.22(minor),60.81(major),46.72(minor),43.98(major),42.65(major),42.39(minor), 39.60(minor),38.29(major),36.33(major),33.32(minor),27.07(major),26.99(minor), 24.20(major),24.16(minor),21.81(major),20.96(minor)；HRMS(ESI-TOF)Calcd for C16H22ClN2O2 +([M+H]+)309.1364.Found 309.1362.
2a5,N-(2-(1-乙酰基-3-甲基-5-苯基吲哚啉-3-基)乙基)-N-甲基乙酰胺,N-(CO)键旋转受阻产生13:5:1:2四个不可分离的旋转异构体混合物(主要异构体和次要异构体分别用 major和minor表示，另外还有2个旋转异构体的含量较少，因而未予表征，仅表征major 和minor异构体)，白色固体：mp 145-146℃.1H NMR(400MHz,CDCl3)δ＝1.44(s,3Hmajor),1.48(s,3H minor),1.85-1.97(stack,2H major and 5H minor),2.02(s,3Hmajor), 2.26(s,3H minor),2.28(s,3H major),2.86(s,3H minor),2.88(s,3H major),3.01-3.11 (stack,1H major and 1H minor),3.21-3.30(m,1H minor),3.46-3.53(m,1Hmajor),3.77(d, J＝10.4Hz,1H major),3.83(d,J＝10.4Hz,1H minor),3.92(d,J＝10.4Hz,1H minor), 4.17(d,J＝10.4Hz,1H major),7.30-7.59(stack,7H major and 7Hminor),8.24(d,J＝8.4 Hz,1H major),8.27(d,J＝8.7Hz,1H minor)；13C{1H}NMR(100MHz,CDCl3)δ＝170.38 (major),169.96(minor),168.82(major),168.46(minor),141.55(major),141.53(minor), 140.92(major),140.68(minor),138.92(major),137.69(minor),137.40(minor),136.98 (major),128.87(minor),128.78(major),127.56(minor),127.21(minor),127.06(major), 127.00(major),126.86(major and minor),120.70(major),120.62(minor),117.38(minor), 117.20(major),61.40(minor),61.07(major),46.88(minor),44.16(major),42.64(major), 42.41(minor),39.91(minor),38.45(major),36.30(major),33.32(minor),27.20(major), 27.14(minor),24.28(major),24.25(minor),21.82(major),20.94(minor)；HRMS(ESI-TOF) Calcd forC22H27N2O2 +([M+H]+)351.2067.Found 351.2079.
2b1,N-(2-(3,5-二甲基-1-丙酰基吲哚啉-3-基)乙基)-N-甲基乙酰胺,DMA N-(CO)键旋转受阻产生2:1不可分离的旋转异构体混合物(另外两个异构体由于酰基苯胺N-(CO)旋转受阻产生，获得量少未予表征)，浅黄色液体。1H NMR(400MHz,CDCl3)δ＝1.21-1.26(stack,3H major and 3H minor),1.36(s,3H major),1.41(s,3H minor),1.76-1.96(stack,2H major and 5H minor),2.02(s,3H major),2.32(s,3H major),2.33(s,3Hminor),2.38-2.56 (stack,2H major and 2H minor),2.84(s,3H minor),2.87(s,3Hmajor),2.91-3.04(stack,1H major and 1H minor),3.14-3.22(m,1H minor),3.42-3.50(m,1H major),3.68(d,J＝10.4 Hz,1H major),3.74(d,J＝10.4Hz,1H minor),3.84(d,J＝10.4Hz,1H minor),4.08(d,J＝ 10.4Hz,1H major),6.91(s,1H major),7.01(d,J＝8.2Hz,1H major,and brs(stack),1H minor),7.05(d,J＝8.3Hz,1H minor),8.09(d,J＝8.3Hz,1H major),8.12(d,J＝8.3Hz, 1H minor)；13C{1H}NMR(100MHz,CDCl3)δ＝171.82(major),171.54(minor),170.32 (major),170.01(minor),140.07(minor),140.04(major),138.13(major),136.95(minor), 133.59(minor),133.22(major),128.99(minor),128.55(major),122.61(major),122.51 (minor),116.84(minor),116.66(major),60.26(minor),60.00(major),46.88(minor),44.15 (major),42.46(major),42.24(minor),39.86(minor),38.41(major),36.26(major),33.27 (minor),29.18(minor),29.14(major),27.14(minor),27.11(major),21.84(major),21.14 (major),21.12(minor),20.89(minor),8.73(major and minor)；HRMS(ESI-TOF)Calcd forC18H27N2O2 +([M+H]+)303.2067.Found 303.2068.
2b2,N-(2-(5-溴-3-甲基-1-丙酰基吲哚啉-3-基)乙基)-N-甲基乙酰胺,DMA N-(CO)键旋转受阻产生3:1不可分离的旋转异构体混合物，浅黄色液体。1H NMR(400MHz,CDCl3)δ＝1.20-1.26(stack,3H major and 3H minor),1.36(s,3H major),1.42(s,3Hminor), 1.77-1.91(stack,2H major and 2H minor),1.94(s,3H minor),2.02(s,3Hmajor),2.38-2.57 (stack,2H major and 2H minor),2.86(s,3H minor),2.90(s,3Hmajor),2.93-3.07(stack,1H major and 1H minor),3.17-3.25(m,1H minor),3.42-3.50(m,1H major),3.70(d,J＝10.4 Hz,1H major),3.77(d,J＝10.4Hz,1H minor),3.87(d,J＝10.4Hz,1H minor),4.15(d,J＝ 10.4Hz,1H major),7.21(s,1H major),7.22(s,1Hminor),7.32(dd,J＝2.0,8.6Hz,1H major),7.36(dd,J＝1.9,8.6Hz,1H minor),8.11(d,J＝8.6Hz,1H major),8.14(d,J＝8.6 Hz,1H minor)；13C{1H}NMR(100MHz,CDCl3)δ＝172.26(major),171.93(minor), 170.39(major),169.92(minor),141.48(major and minor),140.48(major),139.28(minor), 131.42(minor),130.95(major),125.25(major andminor),118.61(minor),118.43(major), 116.22(minor),115.92(major),60.22(minor),59.84(major),46.73(minor),43.99(major), 42.65(major),42.39(minor),39.67(minor),38.40(major),36.32(major),33.30(minor), 29.24(minor),29.19(major),27.10(major),26.99(minor),21.81(major),20.95(minor), 8.60(major and minor)；HRMS(ESI-TOF)Calcd for C17H24BrN2O2 +([M+H]+)367.1016. Found 367.1014.
2b3,N-(2-(5-氯-3-甲基-1-丙酰基吲哚啉-3-基)乙基)-N-甲基乙酰胺,DMA N-(CO)键旋转受阻产生3:1不可分离的旋转异构体混合物，浅黄色液体。1H NMR(400MHz,CDCl3)δ＝1.20-1.26(stack,3H major and 3H minor),1.37(s,3H major),1.42(s,3Hminor), 1.77-1.91(stack,2H major and 2H minor),1.94(s,3H minor),2.02(s,3Hmajor),2.38-2.58 (stack,2H major and 2H minor),2.85(s,3H minor),2.90(s,3Hmajor),2.92-3.07(stack,1H major and 1H minor),3.17-3.25(m,1H minor),3.42-3.50(m,1H major),3.71(d,J＝10.4 Hz,1H major),3.78(d,J＝10.4Hz,1H minor),3.88(d,J＝10.4Hz,1H minor),4.16(d,J＝ 10.4Hz,1H major),7.07(s,1H major),7.08(s,1Hminor),7.17(dd,J＝1.6,8.6Hz,1H major),7.22(dd,J＝1.6,8.6Hz,1H minor),8.16(d,J＝8.6Hz,1H major),8.19(d,J＝8.6 Hz,1H minor)；13C{1H}NMR(100MHz,CDCl3)δ＝172.21(major),171.88(minor), 170.41(major),169.94(minor),140.99(major and minor),140.08(major),138.89(minor), 128.81(minor),128.48(minor),128.44(major),128.02(major),122.35(major and minor), 118.15(minor),117.95(major),60.28(minor),59.90(major),46.74(minor),44.00(major), 42.65(major),42.40(minor),39.64(minor),38.36(major),36.32(major),33.31(minor), 29.20(minor),29.15(major),27.08(major),26.97(minor),21.80(major),20.95(minor), 8.62(major and minor)；HRMS(ESI-TOF)Calcd for C17H24ClN2O2 +([M+H]+)323.1521. Found 323.1521.
2c1,N-甲基-N-(2-(3-甲基-1-辛酰基吲哚啉-3-基)乙基)乙酰胺，DMA N-(CO)键旋转受阻产生2:1不可分离的旋转异构体混合物(另外两个异构体由于酰基苯胺N-(CO)旋转受阻产生，获得量少未予表征)，浅黄色液体.1H NMR(400MHz,CDCl3)δ＝0.89(t,J＝6.7Hz, 3H major and 3H minor),1.26-1.43(stack,11H major and 11H minor),1.70-1.96(stack,4H major and 7H minor),2.02(s,3H major),2.37-2.52(stack,2H majorand 2H minor),2.84(s, 3H minor),2.87(s,3H major),2.91-3.03(stack,1H major and1H minor),3.15-3.23(m,1H minor),3.43-3.50(m,1H major),3.71(d,J＝10.4Hz,1Hmajor),3.77(d,J＝10.4Hz,1H minor),3.87(d,J＝10.4Hz,1H minor),4.09(d,J＝10.4Hz,1H major),7.02-7.13(stack, 2H major and 2H minor),7.19-7.27(stack,1Hmajor and 1H minor),8.22(d,J＝8.2Hz,1H major),8.25(d,J＝8.2Hz,1H minor)；13C{1H}NMR(100MHz,CDCl3)δ＝171.62(major), 171.35(minor),170.31(major),170.00(minor),142.37(minor),142.33(major),138.05 (major),136.84(minor),128.52(minor),128.06(major),123.94(minor),123.67(major), 122.03(major),121.94(minor),117.23(minor),117.05(major),60.37(minor),60.03 (major),46.87(minor),44.17(major),42.50(major),42.26(minor),39.90(minor),38.24 (major),36.24(major),36.14(minor),36.09(major),33.27(minor),31.74(major),31.72 (minor),29.36(major and minor),29.17(major),29.15(minor),27.25(major),27.13(minor),24.61(minor),24.54(major),22.63(major and minor),21.82(major),20.92(minor),14.10 (major),14.09(minor)；HRMS(ESI-TOF)Calcd for C22H35N2O2 +([M+H]+)359.2693.Found 359.2696.
2c2,N-(2-(3,5-二甲基-1-辛酰基吲哚啉-3-基)乙基)-N-甲基乙酰胺,DMA N-(CO)键旋转受阻产生2:1不可分离的旋转异构体混合物(另外两个异构体由于酰基苯胺N-(CO)旋转受阻产生，获得量少未予表征)，浅黄色液体.1H NMR(400MHz,CDCl3)δ＝0.88(t,J＝6.8 Hz,3H major and 3H minor),1.26-1.41(stack,11H major and 11H minor),1.69-1.96(stack, 4H major and 7H minor),2.02(s,3H major),2.32(s,3H major),2.33(s,3H minor), 2.36-2.50(stack,2H major and 2H minor),2.84(s,3H minor),2.88(s,3H major),2.93-3.05 (stack,1H major and 1H minor),3.15-3.23(m,1Hminor),3.42-3.50(m,1H major),3.69(d, J＝10.4Hz,1H major),3.75(d,J＝10.4Hz,1Hminor),3.86(d,J＝10.4Hz,1H minor), 4.07(d,J＝10.4Hz,1H major),6.91(s,1Hmajor),7.01(dd,J＝0.9,8.2Hz,1H major,and brs(stack),1H minor),7.05(dd,J＝0.7,8.1Hz,1H minor),8.09(d,J＝8.3Hz,1H major), 8.11(d,J＝8.3Hz,1H minor)；13C{1H}NMR(100MHz,CDCl3)δ＝171.26(major), 171.00(minor),170.28(major),169.97(minor),140.08(minor),140.03(major),138.19 (major),137.01(minor),133.57(minor),133.20(major),128.95(minor),128.51(major), 122.60(major),122.48(minor),116.93(minor),116.74(major),60.46(minor),60.19 (major),46.87(minor),44.16(major),42.43(major),42.21(minor),39.88(minor),38.23 (major),36.24(major),36.01(minor),35.97(major),33.25(minor),31.73(major),31.70 (minor),29.36(major andminor),29.17(major),29.15(minor),27.14(major),27.07(minor), 24.63(minor),24.57(major),22.62(major and minor),21.82(major),21.12(major and minor),20.87(minor),14.10(major),14.08(minor)；HRMS(ESI-TOF)Calcd for C23H37N2O2 +([M+H]+)373.2850.Found 373.2853.
2c3,N-(2-(5-溴-3-甲基-1-辛酰基吲哚啉-3-基)乙基)-N-甲基乙酰胺,DMA N-(CO)键旋转受阻产生3:1不可分离的旋转异构体混合物，浅黄色液体。1H NMR(400MHz,CDCl3) δ＝0.88(t,J＝6.8Hz,3H major and 3H minor),1.30-1.42(stack,11H majorand 11H minor),1.68-1.75(stack,2H major and 2H minor),1.77-1.90(stack,2Hmajor and 2H minor), 1.94(s,3H minor),2.03(s,3H major),2.36-2.51(stack,2Hmajor and 2H minor),2.86(s, 3H minor),2.90(s,3H major),2.94-3.07(stack,1Hmajor and 1H minor),3.17-3.25(m,1H minor),3.43-3.50(m,1H major),3.71(d,J＝10.4Hz,1H major),3.78(d,J＝10.4Hz,1H minor),3.88(d,J＝10.4Hz,1H minor),4.13(d,J＝10.4Hz,1H major),7.21(d,J＝1.8Hz, 1H major),7.22(d,J＝1.8Hz,1H minor),7.31(dd,J＝2.0,8.6Hz,1H major),7.36(dd,J＝ 2.0,8.6Hz,1H minor),8.11(d,J＝8.6Hz,1H major),8.14(d,J＝8.3Hz,1H minor)；13C{1H}NMR(100MHz,CDCl3)δ＝171.72(major),171.40(minor),170.37(major), 169.90(minor),141.45(major and minor),140.52(major),139.32(minor),131.38(minor), 130.91(major),125.24(major andminor),118.68(minor),118.49(major),116.22(minor), 115.92(major),60.39(minor),59.99(major),46.72(minor),44.00(major),42.61(major), 42.35(minor),39.68(minor),38.21(major),36.32(major),36.03(minor),35.97(major), 33.30(minor),31.72(major),31.69(minor),29.32(minor),29.30(major),29.16(major), 29.13(minor),27.16(major),26.94(minor),24.49(minor),24.42(major),22.63(major andminor),21.82(major),20.96(minor),14.11(major),14.09(minor)；HRMS(ESI-TOF)Calcdfor C22H34BrN2O2 +([M+H]+)437.1798.Found 437.1799.
2c4,N-(2-(5-氯-3-甲基-1-辛酰基吲哚啉-3-基)乙基)-N-甲基乙酰胺,DMA N-(CO)键旋转受阻产生3:1不可分离的旋转异构体混合物，白色固体：mp 96-97℃.1H NMR(400MHz, CDCl3)δ＝0.88(t,J＝6.7Hz,3H major and 3H minor),1.25-1.42(stack,11Hmajor and 11H minor),1.68-1.77(stack,2H major and 2H minor),1.78-1.92(stack,2H major and 2H minor),1.95(s,3H minor),2.03(s,3H major),2.36-2.51(stack,2Hmajor and 2H minor), 2.86(s,3H minor),2.90(s,3H major),2.93-3.07(stack,1Hmajor and 1H minor),3.17-3.28 (m,1H minor),3.43-3.51(m,1H major),3.72(d,J＝10.4Hz,1H major),3.78(d,J＝10.4 Hz,1H minor),3.88(d,J＝10.4Hz,1H minor),4.14(d,J＝10.4Hz,1H major),7.06(d,J＝ 2.0Hz,1H major),7.07(d,J＝2.0Hz,1H minor),7.17(dd,J＝2.2,8.6Hz,1H major),7.22 (dd,J＝2.2,8.6Hz,1H minor),8.16(d,J＝8.6Hz,1H major),8.19(d,J＝8.3Hz,1H minor)；13C{1H}NMR(100MHz,CDCl3)δ＝171.68(major),171.35(minor),170.38 (major),169.92(minor),140.97(major and minor),140.08(major),138.89(minor),128.82 (minor),128.49(minor),128.44(major),128.02(major),122.33(major),122.29(minor), 118.25(minor),118.04(major),60.46(minor),60.06(major),46.73(minor),44.02(major), 42.61(major),42.35(minor),39.67(minor),38.19(major),36.32(major),36.01(minor), 35.95(major),33.32(minor),31.73(major),31.70(minor),29.34(minor),29.32(major), 29.17(major),29.14(minor),27.16(major),26.95(minor),24.52(minor),24.44(major), 22.64(majorand minor),21.83(major),20.97(minor),14.11(major),14.10(minor)；HRMS (ESI-TOF)Calcd for C22H34ClN2O2 +([M+H]+)393.2303.Found 393.2307.
2d1,N-(2-(1-癸酰基-3,5-二甲基吲哚啉-3-基)乙基)-N-甲基乙酰胺,DMA N-(CO)键旋转受阻产生2:1不可分离的旋转异构体混合物(另外两个异构体由于酰基苯胺N-(CO)旋转受阻产生，获得量少未予表征)，浅黄色液体.1H NMR(400MHz,CDCl3)δ＝0.88(t,J＝7.0 Hz,3H major and 3H minor),1.27-1.41(stack,15H major and 15H minor),1.68-1.96(stack, 4H major and 7H minor),2.02(s,3H major),2.32(s,3H major),2.33(s,3H minor), 2.35-2.50(stack,2H major and 2H minor),2.84(s,3H minor),2.88(s,3H major),2.95-3.05 (stack,1H major and 1H minor),3.15-3.23(m,1Hminor),3.42-3.49(m,1H major),3.69(d, J＝10.4Hz,1H major),3.75(d,J＝10.4Hz,1Hminor),3.86(d,J＝10.4Hz,1H minor), 4.07(d,J＝10.4Hz,1H major),6.91(s,1Hmajor),7.00(d,J＝8.1Hz,1H major,and brs (stack),1H minor),7.05(d,J＝8.0Hz,1Hminor),8.09(d,J＝8.3Hz,1H major),8.11(d,J ＝8.3Hz,1H minor)；13C{1H}NMR(100MHz,CDCl3)δ＝171.25(major),171.00(minor), 170.27(major),169.96(minor),140.08(minor),140.02(major),138.19(major),137.01 (minor),133.55(minor),133.19(major),128.94(minor),128.50(major),122.60(major), 122.48(minor),116.92(minor),116.73(major),60.45(minor),60.18(major),46.87(minor), 44.15(major),42.43(major),42.20(minor),39.87(minor),38.23(major),36.23(major), 36.01(minor),35.96(major),33.24(minor),31.87(major),31.85(minor),29.51,29.48,29.46,29.40,29.28,27.14(major),27.06(minor),24.63(minor),24.57(major),22.65(major and minor),21.81(major),21.12(major),21.09(minor),20.86(minor),14.10(major and minor)；HRMS(ESI-TOF)Calcd for C25H41N2O2 +([M+H]+)401.3163.Found401.3165.
2d2,N-(2-(5-溴-1-癸酰基-3-甲基吲哚啉-3-基)乙基)-N-甲基乙酰胺,DMA N-(CO)键旋转受阻产生3:1不可分离的旋转异构体混合物，白色固体：mp 80-81℃.1H NMR(400MHz, CDCl3)δ＝0.88(t,J＝7.0Hz,3H major and 3H minor),1.27-1.42(stack,15Hmajor and 15H minor),1.68-1.73(stack,2H major and 2H minor),1.77-1.90(stack,2H major and 2H minor),1.94(s,3H minor),2.02(s,3H major),2.35-2.51(stack,2Hmajor and 2H minor), 2.86(s,3H minor),2.90(s,3H major),2.94-3.07(stack,1Hmajor and 1H minor),3.17-3.25 (m,1H minor),3.43-3.50(m,1H major),3.71(d,J＝10.4Hz,1H major),3.78(d,J＝10.4 Hz,1H minor),3.87(d,J＝10.4Hz,1H minor),4.13(d,J＝10.4Hz,1H major),7.21(s,1H major),7.22(s,1H minor),7.31(dd,J＝2.0,8.6Hz,1H major),7.36(dd,J＝2.0,8.6Hz,1H minor),8.11(d,J＝8.6Hz,1H major),8.14(d,J＝8.6Hz,1H minor)；13C{1H}NMR(100 MHz,CDCl3)δ＝171.73(major),171.40(minor),170.37(major),169.91(minor),141.46 (major and minor),140.51(major),139.30(minor),131.40(minor),130.94(major),125.24 (major and minor),118.70(minor),118.52(major),116.24(minor),115.93(major),60.41 (minor),60.01(major),46.73(minor),44.01(major),42.62(major),42.36(minor),39.70 (minor),38.22(major),36.32(major),36.05(minor),35.99(major),33.31(minor),31.89 (major),31.87(minor),29.51,29.48,29.36,29.29,27.17(major),26.95(minor),24.50 (minor),24.43(major),22.67(major and minor),21.82(major),20.95(minor),14.12(major andminor)；HRMS(ESI-TOF)Calcd for C24H38BrN2O2 +([M+H]+)465.2111.Found 465.2107.
2e1,N-(2-(1-十二酰基-3,5-二甲基吲哚啉-3-基)乙基)-N-甲基乙酰胺,DMA N-(CO)键旋转受阻产生2:1不可分离的旋转异构体混合物(另外两个异构体由于酰基苯胺N-(CO)旋转受阻产生，获得量少未予表征)，微黄色液体。1H NMR(400MHz,CDCl3)δ＝0.88(t,J＝ 7.0Hz,3H major and 3H minor),1.26-1.41(stack,19H major and 19H minor),1.68-1.97 (stack,4H major and 7H minor),2.02(s,3H major),2.32(s,3H major),2.33(s,3H minor), 2.36-2.50(stack,2H major and 2H minor),2.84(s,3H minor),2.88(s,3H major),2.94-3.05 (stack,1H major and 1H minor),3.15-3.23(m,1Hminor),3.42-3.50(m,1H major),3.69(d, J＝10.4Hz,1H major),3.75(d,J＝10.4Hz,1Hminor),3.86(d,J＝10.4Hz,1H minor), 4.07(d,J＝10.4Hz,1H major),6.92(s,1Hmajor),7.01(d,J＝7.9Hz,1H major,and brs (stack),1H minor),7.05(d,J＝8.1Hz,1Hminor),8.09(d,J＝8.4Hz,1H major),8.11(d,J ＝8.4Hz,1H minor)；13C{1H}NMR(100MHz,CDCl3)δ＝171.27(major),171.01(minor), 170.29(major),169.98(minor),140.07(minor),140.02(major),138.18(major),137.00 (minor),133.57(minor),133.20(major),128.95(minor),128.51(major),122.61(major), 122.49(minor),116.91(minor),116.73(major),60.45(minor),60.17(major),46.88(minor), 44.16(major),42.43(major),42.20(minor),39.87(minor),38.23(major),36.25(major), 36.02(minor),35.97(major),33.25(minor),31.90(major and minor),29.63,29.53,29.41,29.33,27.16(major),27.08(minor),24.63(minor),24.57(major),22.68(major andminor), 21.83(major),21.13(major),21.11(minor),20.88(minor),14.13(major andminor)；HRMS (ESI-TOF)Calcd for C27H45N2O2 +([M+H]+)429.3476.Found 429.3477.
2e2,N-(2-(5-溴-1-十二酰基-3-甲基吲哚啉-3-基)乙基)-N-甲基乙酰胺,DMA N-(CO)键旋转受阻产生3:1不可分离的旋转异构体混合物，白色固体：mp 97-98℃.1H NMR(400 MHz,CDCl3)δ＝0.88(t,J＝7.0Hz,3H major and 3H minor),1.26-1.42(stack,19Hmajor and 19H minor),1.68-1.73(stack,2H major and 2H minor),1.77-1.90(stack,2H major and 2H minor),1.94(s,3H minor),2.02(s,3H major),2.35-2.51(stack,2Hmajor and 2H minor), 2.86(s,3H minor),2.90(s,3H major),2.92-3.07(stack,1Hmajor and 1H minor),3.17-3.25 (m,1H minor),3.43-3.50(m,1H major),3.71(d,J＝10.4Hz,1H major),3.78(d,J＝10.4 Hz,1H minor),3.87(d,J＝10.4Hz,1H minor),4.13(d,J＝10.4Hz,1H major),7.20(d,J＝ 1.6Hz,1H major),7.22(s,1H minor),7.31(dd,J＝2.0,8.6Hz,1H major),7.36(dd,J＝2.0, 8.6Hz,1H minor),8.11(d,J＝8.6Hz,1Hmajor),8.14(d,J＝8.6Hz,1H minor)；13C{1H} NMR(100MHz,CDCl3)δ＝171.71(major),171.39(minor),170.36(major),169.89(minor), 141.46(major and minor),140.51(major),139.31(minor),131.39(minor),130.92(major), 125.23(major and minor),118.69(minor),118.50(major),116.22(minor),115.92(major), 60.39(minor),60.00(major),46.72(minor),44.00(major),42.61(major),42.35(minor), 39.68(minor),38.21(major),36.31(major),36.03(minor),35.98(major),33.29(minor), 31.90(majorand minor),29.62,29.52,29.50,29.35,29.34,27.16(major),26.94(minor), 24.50(minor),24.42(major),22.68(major and minor),21.81(major),20.95(minor),14.13(major and minor)；HRMS(ESI-TOF)Calcd for C26H42BrN2O2 +([M+H]+)493.2424.Found493.2414.
2f1,N-(2-(3,5-二甲基-1-十八酰基-3-基)乙基)-N-甲基乙酰胺,DMA N-(CO)键旋转受阻产生2:1不可分离的旋转异构体混合物(另外两个异构体由于酰基苯胺N-(CO)旋转受阻产生，获得量少未予表征)，白色固体：mp 76-77℃.1H NMR(400MHz,CDCl3)δ＝0.88(t, J＝7.0Hz,3H major and 3H minor),1.26-1.41(stack,31H major and 31H minor),1.69-1.96 (stack,4H major and 7H minor),2.02(s,3H major),2.32(s,3H major),2.33(s,3H minor), 2.35-2.50(stack,2H major and 2H minor),2.84(s,3H minor),2.88(s,3H major),2.95-3.03 (stack,1H major and 1H minor),3.15-3.24(m,1Hminor),3.42-3.49(m,1H major),3.69(d, J＝10.4Hz,1H major),3.75(d,J＝10.4Hz,1Hminor),3.86(d,J＝10.4Hz,1H minor), 4.07(d,J＝10.4Hz,1H major),6.91(s,1Hmajor),7.00(d,J＝7.9Hz,1H major,and brs (stack),1H minor),7.05(d,J＝8.1Hz,1Hminor),8.09(d,J＝8.4Hz,1H major),8.12(d,J ＝8.4Hz,1H minor)；13C{1H}NMR(100MHz,CDCl3)δ＝171.22(major),170.97(minor), 170.25(major),169.94(minor),140.08(minor),140.03(major),138.18(major),137.00 (minor),133.54(minor),133.17(major),128.94(minor),128.50(major),122.59(major), 122.47(minor),116.92(minor),116.73(major),60.45(minor),60.18(major),46.86(minor), 44.16(major),42.43(major),42.20(minor),39.88(minor),38.24(major),36.22(major), 36.01(minor),35.96(major),33.23(minor),31.91(major and minor),29.68,29.64,29.53,29.52,29.41,29.35,27.14(major),27.06(minor),24.63(minor),24.57(major),22.68(major and minor),21.80(major),21.11(major),21.09(minor),20.86(minor),14.11(major and minor)；HRMS(ESI-TOF)Calcd for C33H57N2O2 +([M+H]+)513.4415.Found513.4418.
2f2,N-(2-(5-溴-3-甲基-1-十八酰基吲哚啉-3-基)乙基)-N-甲基乙酰基,DMA N-(CO)键旋转受阻产生3:1不可分离的旋转异构体混合物，白色固体：mp 70-71℃.1H NMR(400 MHz,CDCl3)δ＝0.88(t,J＝7.0Hz,3H major and 3H minor),1.26-1.42(stack,31Hmajor and 31H minor),1.68-1.77(stack,2H major and 2H minor),1.78-1.90(stack,2H major and 2H minor),1.94(s,3H minor),2.02(s,3H major),2.35-2.50(stack,2Hmajor and 2H minor), 2.86(s,3H minor),2.90(s,3H major),2.94-3.07(stack,1Hmajor and 1H minor),3.17-3.25 (m,1H minor),3.43-3.50(m,1H major),3.71(d,J＝10.4Hz,1H major),3.78(d,J＝10.4 Hz,1H minor),3.87(d,J＝10.4Hz,1H minor),4.13(d,J＝10.4Hz,1H major),7.20(d,J＝ 1.5Hz,1H major),7.22(s,1H minor),7.31(dd,J＝2.0,8.6Hz,1H major),7.36(dd,J＝2.0, 8.6Hz,1H minor),8.11(d,J＝8.6Hz,1Hmajor),8.14(d,J＝8.6Hz,1H minor)；13C{1H} NMR(100MHz,CDCl3)δ＝171.72(major),171.39(minor),170.37(major),169.90(minor), 141.46(major and minor),140.51(major),139.30(minor),131.40(minor),130.93(major), 125.23(major and minor),118.70(minor),118.51(major),116.23(minor),115.92(major), 60.40(minor),60.00(major),46.72(minor),44.01(major),42.61(major),42.35(minor), 39.69(minor),38.22(major),36.31(major),36.04(minor),35.98(major),33.30(minor), 31.93(majorand minor),29.70,29.66,29.64,29.53,29.51,29.36,27.16(major),26.95 (minor),24.50(minor),24.43(major),22.69(major and minor),21.81(major),20.95(minor),14.13(major and minor)；HRMS(ESI-TOF)Calcd for C32H54BrN2O2 +([M+H]+)577.3363.Found 577.3376.
2g,N-(2-(3,5-二甲基-1-新戊酰基吲哚啉-3-基)乙基)-N-甲基乙酰胺,DMA N-(CO)键旋转受阻产生2:1不可分离的旋转异构体混合物(另外两个异构体由于酰基苯胺N-(CO)旋转受阻产生，获得量少未予表征)，浅黄色液体。1H NMR(400MHz,CDCl3)δ＝1.36(s,3Hmajor),1.378(s,9H minor),1.381(s,9H major),1.40(s,3H minor),1.74-1.94(stack,2H major and 5H minor),2.03(s,3H major),2.32(s,3H major),2.33(s,3H minor),2.83(s,3H minor),2.87(s,3H major),3.01-3.13(stack,1H major and 1H minor),3.17-3.25(m,1H minor),3.41-3.49(m,1H major),3.86(d,J＝10.3Hz,1H major),3.87(d,J＝10.3Hz,1H minor),4.09(d,J＝10.3Hz,1H minor),4.21(d,J＝10.3Hz,1H major),6.91(s,1H major and 1H minor),7.01(dd,J＝1.0,8.3Hz,1H major),7.05(d,J＝8.4Hz,1H minor),8.09(d, J＝8.2Hz,1H major),8.11(d,J＝8.2Hz,1H minor)；13C{1H}NMR(100MHz,CDCl3)δ＝ 176.28(major),175.98(minor),170.32(major),170.01(minor),141.62(minor),141.55 (major),137.92(major),136.65(minor),133.75(minor),133.44(major),128.83(minor), 128.40(major),122.40(major),122.29(minor),118.42(minor),118.23(major),61.81 (minor),61.51(major),46.89(minor),44.11(major),43.12(major),42.87(minor),40.11 (major and minor),39.16(minor),37.37(major),36.15(major),33.29(minor),27.70(major), 27.66(minor),25.62(major),25.53(minor),21.86(major),21.10(major),21.09(minor), 20.91(minor)；HRMS(ESI-TOF)Calcd for C20H31N2O2 +([M+H]+)331.2380.Found 331.2380.
2h1,5-氯-3-甲基-3-(2-(N-甲基乙酰胺基)乙基)吲哚啉-1-羧酸叔丁酯,DMA N-(CO)键旋转受阻产生15:8不可分离的旋转异构体混合物，浅黄色液体。1H NMR(400MHz,CDCl3) δ＝1.34(s,3H major),1.38(s,3H minor),1.56(s,9H major and 9H minor),1.76-1.93(stack, 2H major and 2H minor),1.96(s,3H minor),2.03(s,3H major),2.86(s,3H minor),2.90(s, 3H major),2.95-3.11(stack,1H major and 1H minor),3.19-3.27(m,1H minor),3.45-3.52 (m,1H major),3.63-3.70(stack,1H major and 1Hminor),3.83(d,J＝7.9Hz,1H minor), 3.93(d,J＝11.3Hz,1H major),7.04(d,J＝2.0Hz,1H major and 1H minor),7.13(dd,J＝ 1.6,8.5Hz,1H major),7.17(dd,J＝1.7,8.6Hz,1H minor),7.36(brs,unexchengeable,1H minor),7.76(brs,unexchengeable,1Hmajor)；13C{1H}NMR(100MHz,CDCl3)δ＝170.34 (major),169.99(minor),152.30(major),152.13(br,minor),140.78(br),139.88(br),138.73 (br,minor),128.22(minor),127.80(major),127.60(minor),127.27(major),122.53(br, major and minor),115.93(minor),115.71(major),82.08(br,minor),81.11(br,major),59.72 (major andminor),46.77(minor),44.03(major),41.80(br,major and minor),39.72(minor),37.74(major),36.22(major),33.27(minor),28.41(major and minor),27.24(br,major), 26.99(minor),21.86(major),20.95(minor)；HRMS(ESI-TOF)Calcd forC19H28ClN2O3 + ([M+H]+)367.1783.Found 367.1784.
2h2,N-(2-(5-氯-1-(乙磺酰基)-3-甲基吲哚啉-3-基)乙基)-N-甲基乙酰胺,DMAN-(CO)键旋转受阻产生5:2不可分离的旋转异构体混合物，微黄色液体。1H NMR(400MHz,CDCl3)δ＝1.37(s,3H major),1.39-1.44(stack,3H major and 6H minor),1.79-1.93(stack, 2H major and 2H minor),1.97(s,3H minor),2.02(s,3H major),2.86(s,3Hminor),2.94(s, 3H major),2.98-3.07(m,1H minor),3.11-3.42(stack,4H major and3H minor),3.70(d,J＝ 10.2Hz,1H major and 1H minor),3.93(d,J＝10.2Hz,1Hminor),4.01(d,J＝10.2Hz,1H major),7.08(d,J＝2.0Hz,1H major),7.09(d,J＝2.0Hz,1H minor),7.14(dd,J＝2.1,8.6 Hz,1H major),7.20(dd,J＝2.1,8.6Hz,1H minor),7.29(d,J＝8.6Hz,1H major),7.30(d, J＝8.6Hz,1H minor)；13C{1H}NMR(100MHz,CDCl3)δ＝170.44(major),170.01 (minor),140.06(major and minor),139.98(major),138.93(minor),128.77(minor),128.71 (minor),128.34(major),128.23(major),123.40(major),123.24(minor),114.38(minor), 114.21(major),61.81(minor),61.55(major),46.60(minor),44.51(minor),44.35(major), 43.90(major),42.72(major),42.43(minor),39.33(minor),37.04(major),36.25(major), 33.30(minor),26.38(major),26.28(minor),21.81(major),20.99(minor),7.75(major and minor)；HRMS(ESI-TOF)Calcd for C16H24ClN2O3S+([M+H]+)359.1191.Found 359.1192.
2j,N-(2-(1-乙酰基-4-氯-3-甲基吲哚啉-3-基)乙基)-N-甲基乙酰胺,DMA N-(CO)键旋转受阻产生5:2不可分离的旋转异构体混合物，浅黄色液体。1H NMR(400MHz,CDCl3)δ＝ 1.51(s,3H major),1.57(s,3H minor),1.82-1.91(m,1H major),2.00(s,3Hminor),2.03(s, 3H major),2.25(s,3H minor),2.26(s,3H major),2.32-2.49(stack,1Hmajor and 2H minor), 2.60-2.68(m,1H major),2.89(s,3H minor),2.95(s,3H major),2.97-3.05(m,1H minor), 3.10-3.18(m,1H minor),3.66(dd,J＝4.4,12.8Hz,1H major),3.72(d,J＝10.6Hz,1H major),3.81(d,J＝10.4Hz,1H minor),3.90(d,J＝10.4Hz,1Hminor),4.24(d,J＝10.5Hz, 1H major),6.97(d,J＝8.0Hz,1H major),7.02(d,J＝8.0Hz,1H minor),7.15(dd,J＝8.1, 8.1Hz,1H major),7.19(dd,J＝8.1,8.1Hz,1H minor),8.18(d,J＝8.1Hz,1H major),8.20 (d,J＝8.1Hz,1H minor)；13C{1H}NMR(100MHz,CDCl3)δ＝170.39(major),170.14 (minor),169.12(major),168.69(minor),144.37(major),144.28(minor),132.86(major), 131.92(minor),129.99(minor),129.92(minor),129.87(major),129.56(major),125.38 (minor),125.04(major),115.76(minor),115.64(major),61.24(minor),60.96(major),47.19 (minor),44.36(major),44.08(major),43.86(minor),36.75(minor),36.41(major),35.26 (major),33.32(minor),26.60(minor),26.36(major),24.42(major and minor),21.76(major), 20.96(minor)；HRMS(ESI-TOF)Calcd for C16H22ClN2O2 +([M+H]+)309.1364.Found 309.1372.
2k,N-(2-(1-乙酰基-5-溴吲哚啉-3-基)乙基)-N-甲基乙酰胺,DMA N-(CO)键旋转受阻产生 4:1不可分离的旋转异构体混合物(另外两个异构体由于酰基苯胺N-(CO)旋转受阻产生，获得量少未予表征)，白色半固态。1H NMR(400MHz,CDCl3)δ＝1.66-1.75(m,1Hmajor),1.81-1.92(m,1H minor),1.97-2.07(stack,1H major and 1H minor),2.08(s,3Hminor),2.10(s,3H major),2.23(s,3H major and 3H minor),2.94(s,3H minor),3.02(s,3H major),3.19-3.44(stack,2H major and 3H minor),3.68-3.76(stack,1H majorand 1H minor), 3.83(dd,J＝6.0,10.6Hz,1H major),4.19-4.26(stack,1H major and1H minor),7.27(s,1H major and 1H minor),7.30(dd,J＝1.5,8.6Hz,1H major),7.35(dd,J＝1.6,8.6Hz,1H minor),8.08(d,J＝8.6Hz,1H major),8.11(d,J＝8.6Hz,1Hminor)；13C{1H}NMR(100 MHz,CDCl3)δ＝170.82(major),170.01(minor),168.91(major),168.57(minor),141.86 (major),141.71(minor),136.80(major),135.70(minor),131.26(minor),130.79(major), 126.67(major and minor),118.53(minor),118.35(major),116.14(minor),115.89(major), 54.95(major),54.76(minor),48.23(minor),44.76(major),37.65(minor),37.50(major), 36.02(major),33.73(minor),33.37(minor),32.71(major),24.19(major and minor),21.85 (major),21.20(minor)；HRMS(ESI-TOF)Calcd for C15H20BrN2O2 +([M+H]+)339.0703. Found 339.0702.
2l,N-(2-(3,5-二甲基-1-辛酰基吲哚啉-3-基)乙基)-N-甲基甲酰胺,DMAN-(CO)键旋转受阻产生3:2不可分离的旋转异构体混合物(另外两个异构体由于酰基苯胺N-(CO)旋转受阻产生，获得量少未予表征)，微黄色液体.1H NMR(400MHz,CDCl3)δ＝0.89(t,J＝6.8Hz,3H major and 3H minor),1.29-1.40(stack,11H major and 11H minor),1.69-1.77(stack, 2H major and 2H minor),1.80-1.95(stack,2H major and 2H minor),2.326(s,3H major), 2.334(s,3H minor),2.36-2.50(stack,2H major and 2H minor),2.80(s,3H minor),2.85(s, 3H major),2.96-3.04(stack,1H major and 1H minor),3.14-3.22(m,1H minor),3.37-3.44 (m,1H major),3.70-3.76(stack,1H major and 1Hminor),3.86(d,J＝10.4Hz,1H minor), 4.04(d,J＝10.5Hz,1H major),6.89(s,1Hminor),6.92(s,1H major),7.01-7.06(stack,1H major and 1H minor),7.91(s,1Hminor),7.96(s,1H major),8.09-8.12(stack,1H major and 1H minor)；13C{1H}NMR(100MHz,CDCl3)δ＝171.27,171.05,162.34,162.30,140.07, 140.02,137.86,136.98,133.63,133.34,129.01,128.70,122.62,122.57,116.96,116.83, 60.55,60.35,45.81,42.48,42.33,40.79,40.09,37.86,36.03,36.01,34.58,31.74,31.73, 29.66,29.38,29.18,29.16,27.18,26.93,24.62,24.60,22.64,21.14,14.10,14.09；HRMS (ESI-TOF)Calcd for C22H35N2O2 +([M+H]+)359.2693.Found 359.2691.
2m,5-((3,5-二甲基-1-辛酰基吲哚啉-3-基)甲基)-1-甲基吡咯烷-2-酮,1:1非对映异构体混合物和5:1旋转异构体混合物，微黄色液体。1H NMR(400MHz,CDCl3)δ＝0.89(t,J＝ 6.9Hz,6H),1.18-1.44(stack,24H),1.54-1.75(stack,8H),2.02-2.30(stack,6H),2.33(s,6H), 2.37-2.42(stack,4H),2.68(s,3H),2.73(s,3H),3.24-3.30(m,1H),3.41-3.47(m,1H),3.76 (dd,J＝10.4,13.3Hz,2H),3.92(d,J＝9.5Hz,2H),6.92(d,J＝9.6Hz,2H),7.05(d,J＝8.3 Hz,2H),8.11(dd,J＝1.7,8.2Hz,2H)；13C{1H}NMR(100MHz,CDCl3)δ＝174.82, 174.48,171.04,170.91,140.13,140.09,137.54,137.38,133.60,133.39,129.01,128.93, 123.15,122.65,117.00,116.95,61.14,60.78,57.47,45.45,44.59,42.57,42.28,36.07,35.99, 31.71,29.95,29.73,29.38,29.15,27.78,27.71,27.52,27.25,26.97,26.11,24.63,24.59, 22.62,21.13,14.09；HRMS(ESI-TOF)Calcd forC24H37N2O2 +([M+H]+)385.2850.Found 385.2854.
2n,N-(2-(1-乙酰基-3-甲基吲哚啉-3-基)乙基)乙酰胺,6:1的旋转异构体混合物，白色固体: mp 130-131℃.1H NMR(400MHz,CDCl3)δ＝1.39(s,3H),1.80-1.93(m,5H),2.24(s, 3H),2.95-3.04(m,1H),3.22-3.36(m,1H),3.74(d,J＝10.4Hz,1H),4.01(d,J＝10.4Hz, 1H),5.30(brs,1H),7.06(dd,J＝7.4,7.4Hz,1H),7.12(d,J＝7.4Hz,1H),7.23(dd,J＝7.4, 8.4Hz,1H),8.20(d,J＝8.1Hz,1H)；13C{1H}NMR(100MHz,CDCl3)δ＝170.09,168.80, 142.04,138.09,128.20,123.92,122.31,117.08,61.03,42.64,41.06,35.99,27.07,24.32, 23.21；HRMS(ESI-TOF)Calcd for C15H21N2O2 +([M+H]+)261.1598.Found261.1591。
Claims (7)
1.一种2,3-二氢色胺类化合物(式II化合物)的合成方法，其特征在于，反应路线如下：
其中：
R1是氢或C1-6烷基；
R2是氢、卤素、C1-6烷基或苯基；
R3是COR7或SO2R8；
R4是氢或C1-6烷基；
R5是氢或C1-6烷基；
R6是氢或C1-6烷基；
R7是C1-17烷基或-O-C1-6烷基；
R8是C1-6烷基；
反应使用的溶剂为酰胺与水形成的混合水相溶剂，其中酰胺与水的体积比为3～5:1；反应温度为115℃～125℃。
2.如权利要求1所述的方法，其特征在于：所述卤素是指氟、氯、溴或碘。
3.如权利要求1所述的方法，其特征在于：所述C1-6烷基选自甲基、乙基、丙基、异丙基、正丁基、异丁基、仲丁基、叔丁基、正戊基、异戊基、新戊基、正己基或异己基；所述C1-17烷基选自甲基、乙基、丙基、异丙基、正丁基、异丁基、仲丁基、叔丁基、正戊基、异戊基、新戊基、正己基、异己基、n-C7H15、n-C9H19、n-C11H23或n-C17H35。
4.如权利要求1所述的方法，其特征在于：所述-O-C1-6烷基选自甲氧基、乙氧基或叔丁氧基。
5.如权利要求1所述的方法，其特征在于：R1选自氢或甲基；R2选自氢、甲基、氯、溴或苯基；R3是COR7；R4是氢、甲基或乙基；R5选自氢、甲基或乙基；R6选自氢、甲基或乙基；R7选自甲基、乙基、叔丁基、n-C7H15、n-C9H19、n-C11H23或n-C17H35。
6.如权利要求1-5任一项所述的方法，其特征在于：所述催化剂DCP的用量为2-3当量。
7.如权利要求1所述的方法，其特征在于：式II化合物选自
N-(2-(1-乙酰基-3-甲基吲哚啉-3-基)乙基)-N-甲基乙酰胺；
N-(2-(1-乙酰基-3,5-二甲基吲哚啉-3-基)乙基)-N-甲基乙酰胺；
N-(2-(1-乙酰基-5-溴-3-甲基吲哚啉-3-基)乙基)-N-甲基乙酰胺；
N-(2-(1-乙酰基-5-氯-3-甲基吲哚啉-3-基)乙基)-N-甲基乙酰胺；
N-(2-(1-乙酰基-3-甲基-5-苯基吲哚啉-3-基)乙基)-N-甲基乙酰胺；
N-(2-(3,5-二甲基-1-丙酰基吲哚啉-3-基)乙基)-N-甲基乙酰胺；
N-(2-(5-溴-3-甲基-1-丙酰基吲哚啉-3-基)乙基)-N-甲基乙酰胺；
N-(2-(5-氯-3-甲基-1-丙酰基吲哚啉-3-基)乙基)-N-甲基乙酰胺；
N-甲基-N-(2-(3-甲基-1-辛酰基吲哚啉-3-基)乙基)乙酰胺；
N-(2-(3,5-二甲基-1-辛酰基吲哚啉-3-基)乙基)-N-甲基乙酰胺；
N-(2-(5-溴-3-甲基-1-辛酰基吲哚啉-3-基)乙基)-N-甲基乙酰胺；
N-(2-(5-氯-3-甲基-1-辛酰基吲哚啉-3-基)乙基)-N-甲基乙酰胺；
N-(2-(1-癸酰基-3,5-二甲基吲哚啉-3-基)乙基)-N-甲基乙酰胺；
N-(2-(5-溴-1-癸酰基-3-甲基吲哚啉-3-基)乙基)-N-甲基乙酰胺；
N-(2-(1-十二酰基-3,5-二甲基吲哚啉-3-基)乙基)-N-甲基乙酰胺；
N-(2-(5-溴-1-十二酰基-3-甲基吲哚啉-3-基)乙基)-N-甲基乙酰胺；
N-(2-(3,5-二甲基-1-十八酰基-3-基)乙基)-N-甲基乙酰胺；
N-(2-(5-溴-3-甲基-1-十八酰基吲哚啉-3-基)乙基)-N-甲基乙酰基；
N-(2-(3,5-二甲基-1-新戊酰基吲哚啉-3-基)乙基)-N-甲基乙酰胺；5-氯-3-甲基-3-(2-(N-甲基乙酰胺基)乙基)吲哚啉-1-羧酸叔丁酯；
N-(2-(5-氯-1-(乙磺酰基)-3-甲基吲哚啉-3-基)乙基)-N-甲基乙酰胺；
N-(2-(1-乙酰基-4-氯-3-甲基吲哚啉-3-基)乙基)-N-甲基乙酰胺；
N-(2-(1-乙酰基-5-溴吲哚啉-3-基)乙基)-N-甲基乙酰胺；
N-(2-(3,5-二甲基-1-辛酰基吲哚啉-3-基)乙基)-N-甲基甲酰胺；
5-((3,5-二甲基-1-辛酰基吲哚啉-3-基)甲基)-1-甲基吡咯烷-2-酮；
N-(2-(1-乙酰基-3-甲基吲哚啉-3-基)乙基)乙酰胺。
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| CN108264474A (zh) * | 2018-02-09 | 2018-07-10 | 浙江师范大学 | 一种色胺及其衍生物的合成方法 |
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| CN108264474A (zh) * | 2018-02-09 | 2018-07-10 | 浙江师范大学 | 一种色胺及其衍生物的合成方法 |
| CN109232316A (zh) * | 2018-11-13 | 2019-01-18 | 昆明学院 | 一类α-三级腈结构β-二羰基化合物的合成方法 |
Non-Patent Citations (4)
| Title |
|---|
| Chawapon Phiphatwatcharaded et al..Anti-Inflammatory Activities of Melatonin Derivatives in Lipopolysaccharide-Stimulated RAW 264.7 Cells and Antinociceptive Effects in Mice.《DRUG DEVELOPMENT RESEARCH》.2014,第75卷第235-245页. * |
| Pham Van Thoai et al..Design and Synthesis of Sustain-Acting Melatonin Prodrugs.《Journal of Chemistry》.2013,第2013卷第1-7页. * |
| Yubin Ji et al..Synthesis of 2,3-Dihydrotryptamines from Amide Solvents and Acyclic Materials through Metal-Free Amidoalkylarylation of Unactivated Alkenes.《Synlett》.2019,第30卷第1329–1333页. * |
| 蒋金之 等.Fischer吲哚合成法的研究进展.《有机化学》.2006,第26卷(第8期),第1025-1030页. * |
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