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Preparation method of N-(indol-N-formyl)-alpha-aminoamide derivatives

A technology of aminoamide and formyl, which is applied in the field of preparation of N--α-aminoamide derivatives, achieving the effect of mild conditions and excellent yield

Active Publication Date: 2019-08-20
ZHEJIANG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Using indole as a potential component of the Ugi reaction, carbon dioxide is used to introduce a carboxyl group on the nitrogen atom at the No. 1 position, and then react with aldehydes, primary amines and isocyanides to obtain the indole skeleton and α The carbonyl-linked product of -aminoamide has not been reported

Method used

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  • Preparation method of N-(indol-N-formyl)-alpha-aminoamide derivatives
  • Preparation method of N-(indol-N-formyl)-alpha-aminoamide derivatives
  • Preparation method of N-(indol-N-formyl)-alpha-aminoamide derivatives

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0040] In a dry two-necked reaction flask, 33 mg (0.2 mmol) of N-indolecarboxylic acid and 36 mg (0.24 mmol) of p-nitrobenzaldehyde were weighed, and 2 mL of solvent (dichloromethane:methanol=1:2) was injected after being protected by an argon balloon. , inject aniline 24mg and benzyl isocyanide 28mg subsequently, the reaction is stirred under ice-water bath for 24 hours, TLC detects that the reaction has been converted completely, and after adding silica gel to mix the sample, column chromatography separation (eluent is petroleum ether: ethyl acetate=5: 1) 74 mg of the product can be obtained with a yield of 73%. The reaction formula is as follows:

[0041]

[0042] The physical properties and spectral data of the product are as follows: white solid, melting point 151–153 °C; 1 HNMR (600MHz, CDCl 3 )δ8.13–8.07(m,2H),8.03(d,J=8.4Hz,1H),7.54(d,J=8.4Hz,2H),7.45(d,J=7.8Hz,1H),7.35– 7.24 (m, 6H), 7.21–7.09 (m, 4H), 7.04–6.93 (m, 3H), 6.84 (d, J=3.6Hz, 1H), 6.25 (d, J=3.6Hz, ...

Embodiment 2

[0044]In a dry two-necked reaction flask, 33 mg (0.2 mmol) of N-indolecarboxylic acid and 26 mg (0.24 mmol) of benzaldehyde were weighed, and 2 mL of solvent (dichloromethane:methanol=1:2) was injected after being protected by an argon balloon, and then injected 24 mg of aniline and 28 mg of benzyl isocyanide were reacted in an ice-water bath and stirred for 24 hours. TLC detected that the reaction was completely converted. After adding silica gel and mixing the sample, column chromatography separation (eluent was petroleum ether: ethyl acetate = 5: 1) could be obtained. The product was obtained in 63 mg with a yield of 69%. The reaction formula is as follows:

[0045]

[0046] The physical properties and spectral data of the product are as follows: white solid, melting point 141–143 °C; 1 H NMR (600MHz, CDCl 3 )δ8.13-8.04(m,1H),7.43(d,J=7.8Hz,1H),7.40-7.36(m,2H),7.32-7.23(m,9H),7.18-7.15(m,1H) ,7.12–7.06(m,3H),7.06–7.00(m,2H),6.87(d,J=3.6Hz,1H),6.50(t,J=5.4Hz,1H),6.22(d...

Embodiment 3

[0048] In a dry two-necked reaction flask, 33 mg (0.2 mmol) of N-indolecarboxylic acid and 49 mg (0.24 mmol) of 3-bromo-4-fluorobenzaldehyde were weighed, and 2 mL of solvent (dichloromethane: methanol = 1:2), inject aniline 24mg and benzyl isocyanide 28mg subsequently, the reaction is stirred under ice-water bath for 24 hours, TLC detects that the reaction has been converted completely, and after adding silica gel to mix the sample, column chromatography separation (eluent is petroleum ether: ethyl acetate) Ester=5:1) 89 mg of product can be obtained, and the yield is 80%. The reaction formula is as follows:

[0049]

[0050] The physical properties and spectral data of the product are as follows: white solid, melting point 134–136 °C; 1 H NMR (400MHz, CDCl 3 )δ8.05(d,J=8.4Hz,1H),7.56(dd,J 1 =6.4Hz,J 2 =2.0Hz,1H),7.44(d,J=7.6Hz,1H),7.34-7.23(m,7H),7.21-7.08(m,4H),7.03-6.92(m,3H),6.83(d, J=3.6Hz, 1H), 6.73(t, J=6.0Hz, 1H), 6.22(d, J=3.6Hz, 1H), 6.00(s, 1H), 4.52(d, J=6...

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Abstract

The invention discloses a preparation method of N-(indol-N-formyl)-alpha-aminoamide derivatives. The method comprises the following steps: N-indolecarboxylic acid compounds, aldehyde compounds, primary amine compounds and isonitrile compounds undergo a four-component reaction in a solvent; or the N-indolecarboxylic acid compounds, cyclic imine compounds and the isonitrile compounds undergo a three-component reaction in the solvent; and post-treatment is carried out after the reaction is completed in order to obtain the N-(indol-N-formyl)-alpha-aminoamide derivatives. The preparation method which uses the indole compounds as a potential component for a classical Ugi reaction to realize the rapid linkage of the indole skeleton and alpha-aminoamide under mild conditions has the advantages ofefficient, simple and rapid reaction, high yield, and far-reaching significance in organic synthesis and medicinal chemistry.

Description

technical field [0001] The invention belongs to the field of organic synthesis, in particular to a preparation method of an N-(indole-N-formyl)-α-aminoamide derivative. Background technique [0002] Indole nucleus is a dominant skeleton in natural products and medicinal chemistry, and compounds containing indole nucleus are often important compounds with biological activity or medicinal value. The Ugi reaction is a classic multi-component reaction in organic synthesis. This reaction successfully synthesizes α-aminoamides from carboxylic acids, carbonyl compounds, primary amines and isonitriles in a one-pot method. It is a non-natural amino acid derivative. Important methods of synthesis ((a) Ugi, I.; Meyr, R.; Fetzer, U.; Steinbrückner, C. Angew. Chem. 1959, 71, 386. (b) Ugi, I.; .1960, 72, 267. (c) Ugi, I. Angew. Chem., Int. Edit. 1962, 1, 8.), the classic Ugi reaction formula is as follows: [0003] [0004] Ugi reactions have been developed for more than sixty years,...

Claims

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Application Information

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IPC IPC(8): C07D209/08C07D401/12C07D403/12C07D405/12C07D409/12C07D209/42C07D209/32C07D209/30C07D487/04
CPCC07D209/08C07D401/12C07D403/12C07D405/12C07D409/12C07D209/42C07D209/32C07D209/30C07D487/04
Inventor 崔孙良曾林伟
Owner ZHEJIANG UNIV
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