A kind of preparation method of N-(indole-n-formyl)-alpha-aminoamide derivative

A kind of aminoamide, formyl technology, applied in the field of preparation of N--α-aminoamide derivatives, to achieve the effect of large application potential

Active Publication Date: 2021-12-17
ZHEJIANG UNIV
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  • Abstract
  • Description
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  • 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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  • A kind of preparation method of N-(indole-n-formyl)-alpha-aminoamide derivative
  • A kind of preparation method of N-(indole-n-formyl)-alpha-aminoamide derivative
  • A kind of preparation method of N-(indole-n-formyl)-alpha-aminoamide derivative

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0040] Weigh 33 mg (0.2 mmol) of N-indolecarboxylic acid and 36 mg (0.24 mmol) of p-nitrobenzaldehyde into a dry two-necked reaction flask, and inject 2 mL of solvent after being protected by an argon balloon (dichloromethane: methanol = 1:2) , followed by injecting 24 mg of aniline and 28 mg of benzyl isonitrile, reacting in an ice-water bath and stirring for 24 hours, TLC detected that the reaction was transformed completely, adding silica gel to mix the sample and separating by column chromatography (eluent was 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 spectrogram 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,1H),6.11 (s,1H),4.5...

Embodiment 2

[0044]Weigh 33 mg (0.2 mmol) of N-indolecarboxylic acid and 26 mg (0.24 mmol) of benzaldehyde into a dry two-necked reaction flask, inject 2 mL of solvent (dichloromethane: methanol = 1:2) after argon balloon protection, and then inject 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 to mix the sample, column chromatography separated (eluent: petroleum ether: ethyl acetate = 5: 1) 63 mg of the product was obtained, and the yield was 69%. The reaction formula is as follows:

[0045]

[0046] The physical properties and spectrogram 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,J=3.6 Hz,1H),6.03(s,1H),4.62–4.48(m,2H); 13 C...

Embodiment 3

[0048] 33 mg (0.2 mmol) of N-indolecarboxylic acid and 49 mg (0.24 mmol) of 3-bromo-4-fluorobenzaldehyde were weighed into a dry two-necked reaction flask, and 2 mL of solvent (dichloromethane:methanol = 1:2), followed by injecting 24 mg of aniline and 28 mg of benzyl isonitrile, reacted and stirred for 24 hours in an ice-water bath, TLC detected that the reaction had transformed completely, added silica gel to mix the sample and separated by column chromatography (eluent was petroleum ether: ethyl acetate Ester=5:1) 89 mg of the product can be obtained, and the yield is 80%. The reaction formula is as follows:

[0049]

[0050] The physical properties and spectrogram 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,...

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Abstract

The invention discloses a preparation method of N-(indole-N-formyl)-α-aminoamide derivatives, which comprises the following steps: N-indole carboxylic acid compounds, aldehyde compounds, primary amine compounds and The four-component reaction of the isonitrile compound in the solvent; or the three-component reaction of the N-indole carboxylic acid compound, the cyclic imine compound and the isonitrile compound in the solvent. After the reaction is completed, the post-treatment obtains the N-(indole-N-formyl)-α-aminoamide derivative; the preparation method uses the indole compound as a potential component of the classic Ugi reaction, in mild The rapid connection of indole skeleton and α-aminoamide is realized under the conditions, the reaction is efficient, concise and fast, and the yield is high, which has far-reaching significance for organic synthesis and medicinal chemistry.

Description

technical field [0001] The invention belongs to the field of organic synthesis, and in particular relates to a preparation method of N-(indole-N-formyl)-α-aminoamide derivatives. Background technique [0002] The indole core is a dominant skeleton in natural products and medicinal chemistry, and the compounds containing the indole core 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 one pot. It is an unnatural amino acid derivative. Important methods of synthesis ((a) Ugi, I.; Meyr, R.; Fetzer, U.; Steinbrückner, C. Angew. Chem. 1959, 71, 386. (b) Ugi, I.; Steinbrückner, C. Angew. Chem. .1960,72,267.(c)Ugi,I.Angew.Chem.,Int.Edit.1962,1,8.), the classic Ugi reaction is as follows: [0003] [0004] The Ugi reaction has been developed for mor...

Claims

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Application Information

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Patent Type & Authority Patents(China)
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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