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A kind of synthetic method of novel indole glycine derivative

A technology of indole glycine and indole derivatives, which is applied in organic chemistry and other fields, can solve the problems such as the difficulty of hydrolysis into amino acids, and achieve the effects of cheap and easy to obtain oxidants, low toxicity of reaction raw materials, and a wide range of effects

Active Publication Date: 2018-12-04
CHANGZHOU UNIV
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

In 2012, Yu Xiaoqiang’s research group at Dalian University of Technology reported the cross-dehydrogenation coupling reaction between indole and 2-(disubstituted amino) acetate under mCPBA conditions, and obtained a series of indole glycine derivatives [J.Org .Chem.2012,77,7114.], but the obtained indole glycine derivative has an alkyl group on the nitrogen, and it is very difficult to hydrolyze it into an amino acid by breaking the C-N bond

Method used

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  • A kind of synthetic method of novel indole glycine derivative
  • A kind of synthetic method of novel indole glycine derivative
  • A kind of synthetic method of novel indole glycine derivative

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0036]

[0037] With indole, diethyl benzamidomalonate as raw material, according to indole: diethyl benzamidomalonate: copper acetate mol ratio is 1:1.25:2.5, solvent DMSO consumption is 3mL, in N 2 Heating to 80° C. under protective conditions, TLC detected that the reaction was progressing, and after the reaction of all raw materials was complete, the pure product 3aa was obtained by column chromatography.

[0038]The resulting product is tested, and the instrument used for the test is: AVANCE 300MHz type nuclear magnetic resonance instrument (Bruker company, TMS is internal standard); Japan Shimadzu LCMS-2020 type mass spectrometer; SGW X-4 micro melting point instrument (thermometer without Correction). The test method of other embodiments is the same as this embodiment.

[0039] 3aa: white solid, mp 147-148℃.1H NMR (300MHz, CDCl3) δ8.51br, 1H), 8.09(s, 1H), 7.85(d, J=7.0Hz, 2H), 7.77-7.81(m, 1H), 7.67(d, J=7.2Hz, 1H), 7.52(tt, J=7.3Hz, 1.3Hz, 1H), 7.44(t, J=7.5Hz, ...

Embodiment 2

[0041]

[0042] With 5-methoxyindole, diethyl benzamidomalonate as raw material, according to 5-methoxyindole: diethyl benzamidomalonate: copper acetate molar ratio is 1:1.25 : 2.5, the solvent acetonitrile consumption is 3mL, in N 2 Heating to 80° C. under protective conditions, TLC detection of the progress of the reaction, after the complete reaction of all raw materials, the pure product 3ab was obtained by column chromatography.

[0043] 3ab: white solid, mp 159-160℃. 1 H NMR (300MHz, CDCl 3 )δ8.42(br,1H),8.06(s,1H),7.86(d,J=6.9Hz,2H),7.74(d,J=2.8Hz,1H),7.52(tt,J=7.3Hz, 1.3Hz, 1H), 7.44(t, J=7.5Hz, 2H), 7.09-7.15(m, 2H), 6.75(dd, J=8.9Hz, 2.3Hz, 1H), 4.21-4.43(m, 4H) ,3.78(s,3H),1.25(t,J=7.1Hz,6H); 13 C NMR (75MHz, CDCl 3 )δ167.8, 166.0, 153.9, 133.5, 132.1, 131.6, 128.8, 127.3, 127.1, 125.4, 112.4, 111.7, 108.5, 102.1, 65.4, 63.0, 55.9, 14.1.

Embodiment 3

[0045]

[0046] With 7-methylindole and diethyl benzamidomalonate as raw materials, according to 7-methylindole: diethyl benzamidomalonate: copper acetate molar ratio is 1:1.25:2.5 , the amount of solvent DMSO is 3mL, in N 2 Heating to 80° C. under protective conditions, TLC detection of the progress of the reaction, after the complete reaction of all raw materials, the pure product 3ac was obtained by column chromatography.

[0047] 3ac: white solid, mp 193-194℃. 1 H NMR (300MHz, CDCl 3 )δ8.61(br,1H),8.14(s,1H),7.86(d,J=7.3Hz,3H),7.40-7.54(m,4H),6.95(t,J=7.2Hz,1H), 6.84(d, J=7.1Hz, 1H), 4.20-4.40(m, 4H), 2.21(s, 3H), 1.23(t, J=7.1Hz, 6H); 13 CNMR (75MHz, CDCl 3 )δ167.8, 166.1, 135.7, 133.6, 132.0, 128.7, 127.3, 126.9, 124.5, 122.0, 121.3, 119.8, 117.1, 108.8, 65.4, 62.9, 16.3, 14.1.

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Abstract

The invention relates to a synthetic method of novel indole glycine derivatives. Raw materials adopted in the method include indole, amidomalonate and an oxidizing agent. The synthetic method includes the steps that indole, amidomalonate and the oxidizing agent are heated to 60-100 DEG C in an organic solvent under the protection of nitrogen, a dehydrogenation cross-coupling reaction occurs, and rich novel indole glycine derivatives are obtained. The substrate range is very wide, the functional group compatibility is good, and the indole glycine derivatives can be obtained from various kinds of substitutional indole and amidomalonate with a high yield. The synthetic method has the advantages that the synthetic route is short, the reaction raw materials are low in toxicity, the reaction time is short, the oxidizing agent is cheap and easy to obtain, and separation and purification are convenient, and has important practical application value in synthesis of such compounds.

Description

technical field [0001] The invention relates to the field of organic chemical industry, in particular to a method for synthesizing novel indole amino acid derivatives. Background technique [0002] Indole glycine derivatives are important intermediates and building blocks for drug development and natural product synthesis [J.Med.Chem.1988,31,1244.; J.Nat.Prod.1998,61,660.], and their synthetic methods have been obtained Certain concerns [Synthesis 2005, 13, 2198.]. The most commonly used method is to directly obtain indole and imine through Mannich-type Friedel–Crafts reaction [Chem.Commun.2010,46,1550.; Org.Lett.2008,10,933.]. [0003] Cross dehydrocoupling (CDC) reaction is one of the most effective means to form carbon-carbon bonds, carbon-nitrogen bonds and carbon-oxygen bonds, and has been widely used in many fields of organic chemistry. Among them, the cross-dehydrogenation coupling reaction of indole 3-position C-H and amine α-position C-H has attracted much attenti...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D209/20C07D405/12
CPCC07D209/20C07D405/12
Inventor 刘锐缪春宝杨海涛
Owner CHANGZHOU UNIV