A kind of preparation method of pyrimido[1,6-a]indole heterocyclic derivative

A technology of 6-a and derivatives, applied in the direction of organic chemistry, can solve the problems of complex synthesis process, harsh reaction conditions, rare reaction raw materials, etc., and achieve the effects of high reaction yield, easy purification, and easy preparation

Inactive Publication Date: 2016-10-05
GUANGDONG UNIV OF TECH
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Problems solved by technology

[0004] However, there are relatively few synthetic methods of pyrimido[1,6-a]indole heterocyclic derivatives reported at present, and the synthetic process is relatively complicated and difficult, and there are many problems, such as: (1) The reaction raw materials are relatively rare, It needs to be obtained through a multi-step synthetic route; (2) the reaction conditions are too harsh, the reaction temperature is too high, and the synthesis yield is low, etc.

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  • A kind of preparation method of pyrimido[1,6-a]indole heterocyclic derivative
  • A kind of preparation method of pyrimido[1,6-a]indole heterocyclic derivative
  • A kind of preparation method of pyrimido[1,6-a]indole heterocyclic derivative

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Embodiment 1

[0055] 1. The synthetic method of pyrimido[1,6-a]indole heterocyclic derivatives, comprising the following steps:

[0056](1) In a 10ml reaction tube, sequentially add 5-bromoindole (38.8mg, 0.2mmol), 1,1'-carbonyldiimidazole (35.6mg, 0.22mmol), 4-dimethylaminopyridine (5mg) and acetonitrile (2 mL), the mixture was refluxed at 80° C. for 6 h. After the reaction solution was cooled to room temperature, benzylamine (21.4 mg, 0.2 mmol) was added, and the temperature was raised to 80° C. for reflux reaction for 8 h. After the reaction was completed, the solvent acetonitrile was directly spin-dried, and the obtained crude product was separated through a silica gel column (petroleum ether: ethyl acetate = 4:1) to obtain 55 mg of N-formylbenzylamide (5-bromo)indole;

[0057]

[0058] (2) In a 10ml reaction tube, add [Cp*RhCl 2 ] 2 (1.6mg, 2.5mol%), AgSbF 6 (5.1mg, 10mol%), N-formylbenzylamide (5-bromo)indole (32.8.0mg, 0.1mmol), ethyl acetoacetate diazo (30.8mg, 0.2mmol), piva...

Embodiment 2

[0065] 1. The synthetic method of pyrimido[1,6-a]indole heterocyclic derivatives, comprising the following steps:

[0066] (1) In a 10ml reaction tube, add 5-methoxyindole (29.4mg, 0.2mmol), 1,1'-carbonyldiimidazole (35.6mg, 0.22mmol), 4-dimethylaminopyridine ( 5mg) and acetonitrile (2mL), the mixture was refluxed at 80°C for 6h. After the reaction solution was cooled to room temperature, benzylamine (21.4 mg, 0.2 mmol) was added, and the temperature was raised to 80° C. for reflux reaction for 8 h. After the reaction, the solvent acetonitrile was directly spin-dried, and the obtained crude product was separated through a silica gel column (petroleum ether: ethyl acetate = 3:1) to obtain 46.5 mg of N-formylbenzylamide (5-methoxy)indole;

[0067]

[0068] (2) In a 10ml reaction tube, add [Cp*RhCl 2 ] 2 (1.6mg, 2.5mol%), AgSbF 6 (5.1mg, 10mol%), N-formylbenzylamide (5-methoxy) indole (28.0mg, 0.1mmol), ethyl acetoacetate diazo (30.8mg, 0.2mmol), pivalic acid (5.1 mg, 50m...

Embodiment 3

[0075] 1. The synthetic method of pyrimido[1,6-a]indole heterocyclic derivatives, comprising the following steps:

[0076] (1) In a 10ml reaction tube, add 7-methoxyindole (29.4mg, 0.2mmol), 1,1'-carbonyldiimidazole (35.6mg, 0.22mmol), 4-dimethylaminopyridine ( 5mg) and acetonitrile (2mL), the mixture was refluxed at 80°C for 6h. After the reaction solution was cooled to room temperature, benzylamine (21.4 mg, 0.2 mmol) was added, and the temperature was raised to 80° C. for reflux reaction for 8 h. After the reaction was completed, the solvent acetonitrile was directly spin-dried, and the obtained crude product was separated through a silica gel column (petroleum ether: ethyl acetate = 3:1) to obtain 44.8 mg of N-formylbenzylamide (7-methoxy)indole;

[0077]

[0078] (2) In a 10ml reaction tube, add [Cp*RhCl 2 ] 2 (1.6mg, 2.5mol%), AgSbF 6 (5.1mg, 10mol%), N-formylbenzylamide (7-methoxy) indole (28.0mg, 0.1mmol), ethyl acetoacetate diazo (30.8mg, 0.2mmol), pivalic acid...

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Abstract

The invention discloses a preparation method of a pyrimidine [1,6-a] indole heterocyclic derivative. The method comprises the following steps: under the condition that a rhodium catalyst, an additive silver salt and an additive acid exist, enabling an N-formamide indole compound and an a-carbonyl diazo compound to perform a cascade reaction in an organic solvent, and after the reaction is ended, separating and purifying to obtain the pyrimidine [1,6-a] indole heterocyclic derivative. The preparation method is mild in reaction condition, anhydrous and anaerobic conditions are not needed, and the operation is simple and convenient; besides, the reaction materials are easily prepared, and the substrate application scope is wide. By-products in the reaction only include nitrogen and water, and an economical, practical, green and environment-friendly novel method is provided for synthesizing the pyrimidine [1,6-a] indole heterocyclic derivative.

Description

technical field [0001] The invention belongs to the technical field of organic synthesis. More specifically, it relates to a preparation method of pyrimido[1,6-a]indole heterocyclic derivatives. Background technique [0002] Nitrogen heterocyclic compounds widely exist in natural products and have good pharmaceutical and biological activities. Most of the existing drug structures contain various types of nitrogen heterocyclic skeletons. Pyrimidine compounds are an important class of substances in life activities, and widely exist in the human body and other organisms. For example, common components in genetic material nucleic acids contain three kinds of pyrimidine structures. In addition, indole derivatives have important applications in drug design. Therefore, with the combined ring structure of these two nitrogen-containing heterocyclic compounds, that is, compounds with pyrimido[1,6-a]indole heterocyclic structural units are effective in antimalarial, anti-inflammatory...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D487/04
CPCC07D487/04
Inventor 曾华强陈训曾伟
Owner GUANGDONG UNIV OF TECH
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