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Indoline aza-eight-membered ring derivative and synthesis method thereof

A synthesis method and an indoline technology are applied in the field of synthesis of indolino aza eight-membered ring derivatives, which can solve the problems of restricting research on indoline compounds, complex compound structures, and difficult construction, etc. Simple and convenient, strong biological activity, environmental friendly effect

Pending Publication Date: 2020-08-28
EAST CHINA NORMAL UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the structure of this type of compound is complex, especially the construction of the core unit indoline aza eight-membered ring is very difficult, and the reported methods generally require multi-step synthesis and are cumbersome, which severely limits the research on the indoline aza eight-membered ring. Structure of Indoline Compounds

Method used

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  • Indoline aza-eight-membered ring derivative and synthesis method thereof
  • Indoline aza-eight-membered ring derivative and synthesis method thereof
  • Indoline aza-eight-membered ring derivative and synthesis method thereof

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0050] Embodiment 1: the synthesis of IA

[0051]

[0052] Under air, 3-(2-(1H-indol-1-yl)phenyl)-3-oxopropanenitrile (0.2mmol), ZnI 2(0.01mmol) and toluene (0.2mL), reacted at 80°C for 2 hours, then added acetylene ketone (0.2mmol), Cs 2 CO 3 (0.4mmol) and DMSO (2.0mL), continue to react at 80°C for 6 hours to obtain the target product formula (IA), a yellow solid, and the isolated yield is 77%. mp 246-248°C.

[0053] NMR data:

[0054] 1 H NMR (400MHz, CDCl 3 )δ17.67(s,1H),7.50(d,J=8.0Hz,1H),7.42(d,J=8.0Hz,1H),7.37-7.19(m,7H),7.16-7.03(m,7H ),6.98(d,J=7.6Hz,1H),6.87-6.79(m,1H),5.90-5.75(m,1H),3.82(dd,J 1 =15.2Hz,J 2 =15.6Hz,1H),3.46(dd,J 1 =15.2Hz,J 2 =15.2Hz,1H). 13 C NMR (100MHz, CDCl 3 )δ185.40,181.71,153.44,139.36,132.03,130.21,129.20,124.91,124.75,124.33,123.59,123.16,122.17,122.03,121.33,121.21,120.94,120.80,118.23,116.04,115.46,113.33,110.34,106.27,104.81 ,102.26,57.49,28.23.

[0055] High-resolution mass spectrometry data: HRMS (ESI) calcd for C 32 ...

Embodiment 2

[0056] Embodiment 2: the synthesis of IB

[0057]

[0058] Under air, 3-(2-(1H-indol-1-yl)-5-methylphenyl)-3-oxopropanenitrile (0.2mmol), ZnI 2 (0.01mmol) and toluene (0.2mL), reacted at 80°C for 2 hours, then added acetylene ketone (0.2mmol), Cs 2 CO 3 (0.4mmol) and DMSO (2.0mL), continue to react at 80°C for 6 hours to obtain the target product formula (IB), a yellow solid, with an isolated yield of 83%. mp 234-236°C.

[0059] NMR data:

[0060] 1 H NMR (400MHz, CDCl 3 )δ17.70(s,1H),7.38(d,J=8.4Hz,1H),7.30-7.02(m,14H),6.92(d,J=8.0Hz,1H),6.84-6.76(m,1H ), 5.79(t, J=10.4Hz, 1H), 3.86-70(m, 1H), 3.43(dd, J 1 =15.6Hz,J 2 =15.6Hz,1H),2.32(s,1H). 13 C NMR (100MHz, CDCl 3 )δ192.50,188.76,160.32,146.63,137.31,136.44,136.27,132.74,132.71,131.83,131.10,130.60,130.09,129.08,128.30,128.18,127.90,127.79,125.15,122.47,119.98,117.37,113.29,111.89,109.04 ,64.47,35.18,20.34.

[0061] High-resolution mass spectrometry data: HRMS (ESI) calcd for C 33 h 25 N 2 o 2 [M+H] + :4...

Embodiment 3

[0062] Embodiment 3: the synthesis of IC

[0063]

[0064] Under air, add 3-(5-bromo-2-(1H-indol-1-yl)phenyl)-3-oxopropanenitrile (0.2mmol), ZnI 2 (0.01mmol) and toluene (0.2mL), reacted at 80°C for 2 hours, then added acetylene ketone (0.2mmol), Cs 2 CO 3 (0.4mmol) and DMSO (2.0mL), continue to react at 80°C for 6 hours to obtain the target product formula (IC), a yellow solid, and the isolated yield is 66%. mp 236-238℃.

[0065] NMR data:

[0066] 1 H NMR (400MHz, CDCl 3 )δ17.70(s,1H),7.54(s,1H),7.46-7.34(m,2H),7.32-7.04(m,12H),6.94(d,J=8.0Hz,1H),6.88-6.80 (m,1H),5.79(t,J=10.4Hz,1H),3.82(dd,J 1 =15.6Hz,J 2 =16.0Hz, 1H), 3.46(dd, J 1 =15.2Hz,J 2 =15.6Hz, 1H). 13 C NMR (100MHz, CDCl 3 )δ190.86188.63,160.31,145.85,138.25,136.88,135.80,134.66,132.98,132.89,132.12,130.40,129.24,129.08,128.37,128.34,127.99,127.87,125.35,123.90,120.80,117.18,115.13,113.11,111.48 ,109.27,64.51,35.22.

[0067] High-resolution mass spectrometry data: HRMS (ESI) calcd for C 32 h 22 B...

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Abstract

The invention discloses an indoline aza-eight-membered ring derivative as shown in a formula (I) and a synthesis method thereof, and the indoline aza-eight-membered ring derivative as shown in the formula (I) is synthesized by taking an indole compound and an acetylenic ketone compound as raw materials under the catalysis of zinc and the promotion of subsequent alkali. The preparation method has the advantages of simple and easily available raw materials, good universality, high atom economy, simple post-treatment, good yield, environmental friendliness and the like. The indoline aza-eight-membered ring skeleton is an important structural unit in many natural product molecules, and most of the compounds have relatively strong biological activity and have important research value in the aspect of drug synthesis.

Description

technical field [0001] The invention belongs to the technical field of organic compounds and synthesis, and relates to a synthesis method of indoline aza eight-membered ring derivatives catalyzed by zinc and promoted by alkali. Background technique [0002] Indolinoaza eight-membered ring skeletons widely exist in natural product molecules. For example, Manzamine A, an indoline alkaloid, was isolated from the sponge Haliclona sp. by the chemist Higa et al. in 1986, and there have been a lot of reports on its synthesis and properties. For example: literature (1) Winkler, J.D.; Axton, J.M.J.Am.Chem.Soc.1998, 120, 6425. (2) Humphrey, J.M.; Liao, Y.; .-L.; Chen, H.-J.; Courtney, A.K.; Martin, S.F.J.Am.Chem.Soc.2002, 124, 8584. (3) Bonazzi, S.; Cheng, B.; ,D.A.J.Am.Chem.Soc.2013,135,9338. Studies have found that this type of compound has a wide range of biological activities, such as insecticidal, antibacterial, anti-inflammatory, antiviral, antimalarial, etc. However, the str...

Claims

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Application Information

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IPC IPC(8): C07D487/04C07D519/00
CPCC07D487/04C07D519/00
Inventor 李艳忠袁洋王野穆远洋杨亚婕王孟丹尹利强
Owner EAST CHINA NORMAL UNIVERSITY