Quinazoline derivatives and their preparation methods and applications

A derivative, quinazoline technology, used in drug combination, organic chemistry, antitumor drugs, etc.

Active Publication Date: 2021-07-06
JIANGXI NORMAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0009] After literature research, we found that there is no very effective method for synthesizing 4-(N-indolyl)-quinazoline derivatives

Method used

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  • Quinazoline derivatives and their preparation methods and applications
  • Quinazoline derivatives and their preparation methods and applications
  • Quinazoline derivatives and their preparation methods and applications

Examples

Experimental program
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preparation example Construction

[0052] The preparation method of the present invention may also include various post-treatment methods commonly used in the art, such as filtration, purification and other steps. The present invention has no special limitation on the post-processing steps. For example, in the present invention, the mixture obtained after the contact reaction can be filtered to remove the filter residue, and then the obtained filtrate is concentrated and purified by column chromatography.

[0053] The third aspect of the present invention provides quinazoline derivatives prepared by the method described in the aforementioned second aspect.

[0054] And, the fourth aspect of the present invention provides the use of the quinazoline derivatives described in the first and third aspects as antibacterial and / or antitumor agents.

[0055] In the present invention, only a small amount of catalyst is used to make the conversion rate of the reaction raw material reach 100%. Simultaneously, the reactio...

Embodiment 1

[0061] Embodiment 1: preparation compound 1a

[0062] Under nitrogen protection, 4-(4-p-methylbenzenesulfonyl)-2-p-tolylquinazoline (0.20mmol), indole (0.22mmol), palladium trifluoroacetate (0.01mmol), 2-bicyclohexyl Phosphine-2',6'-dimethoxybiphenyl (0.02mmol), potassium carbonate (0.40mmol) and 2.0mL toluene were added to the reaction flask, and the reaction was carried out on a magnetic stirrer at 110°C for 6h, and the reaction was detected by TLC. . After the reaction was completed, the catalyst was removed by suction filtration through a sand core funnel equipped with silica gel, and the obtained filtrate was separated by silica gel column chromatography with a volume ratio of petroleum ether and ethyl acetate of 50:1 to obtain the pure product 4-(N-indole Indolyl)-2-p-tolylquinazoline is compound 1a. Yield: 83%.

[0063]Compound 1a is a white solid with a melting point of 167-168°C. 1 H NMR (400MHz, CDCl 3 )δ2.44(s,3H),6.83(d,J=3.2Hz,1H),7.26-7.34(m,4H),7.53(t,J=7.6...

Embodiment 2

[0066] Embodiment 2: preparation compound 1b

[0067] The present embodiment adopts the method similar to embodiment 1 to carry out, the difference is, the present embodiment adopts 4-(4-p-methylbenzenesulfonyl)-2-m-tolylquinazoline (0.20mmol) to replace the embodiment 4-(4-p-Tolylsulfonyl)-2-p-tolylquinazoline (0.20 mmol) in 1. All the other are the same as in Example 1.

[0068] The product 4-(N-indolyl)-2-m-tolylquinazoline was obtained, namely compound 1b. Yield: 85%.

[0069] Compound 1b is a white solid with a melting point of 164-165°C. 1 H NMR (400MHz, CDCl 3 )δ2.46(s,3H),6.81(d,J=3.4Hz,1H),7.24-7.33(m,3H),7.40(t,J=7.6Hz,1H),7.49(t,J=8.2 Hz,1H),7.69-7.72(m,2H),7.84(t,J=8.4Hz,1H),7.96(d,J=7.6Hz,1H),8.04(d,J=8.0Hz,1H), 8.13(d,J=8.4Hz,1H),8.43-8.47(m,2H). 13 C NMR (100MHz, CDCl 3 )δ21.6, 106.7, 113.6, 117.4, 121.2, 122.2, 123.6, 125.5, 126.0, 127.2, 128.55, 128.6, 129.26, 129.3, 130.2, 131.8, 134.0, 136.5, 1357.6, 130.10.3, 15

[0070] IR(KBr):2916,1616,1413,1130...

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Abstract

The invention relates to the field of organic chemistry, and discloses a quinazoline derivative, a preparation method and application thereof. The derivative has a structure represented by formula (1). The method provided by the invention comprises: under alkaline condition, in ligand and selected from palladium trifluoroacetate, tetrakis (triphenylphosphine) palladium, bistriphenylphosphine palladium dichloride, three (dibenzylidene acetone) ) In the presence of at least one catalyst in dipalladium and palladium acetate, the compound shown in formula (I) is reacted with the compound shown in formula (II), and the ligand is 2-bicyclohexylphosphine-2', 6'-Dimethoxybiphenyl. The quinazoline derivatives provided by the invention have excellent antibacterial activity and antitumor activity. The preparation method provided by the invention has high yield, wide substrate applicability, mild reaction conditions, simple operation, low cost, few by-products, high product purity, is applicable to large-scale preparation, and has considerable application prospects.

Description

technical field [0001] The invention relates to the field of organic chemistry, in particular to quinazoline derivatives, a method for preparing quinazoline derivatives, quinazoline derivatives prepared by the method, and quinazoline derivatives as antibacterial agents and / or antibacterial agents. Application of tumor agents. Background technique [0002] Quinazolines are an important class of natural products. Compounds containing quinazoline skeletons have a variety of pharmacological and biological activities, such as: anti-inflammatory, antibacterial, anti-tuberculosis, anti-diabetic, anti-HIV and anti-tumor effects [(a) Cao, S.L.; Feng, Y.P.; Jiang, Y.Y ; Liu, S.Y.; Ding, G.Y.; Li, R.T. Bioorg. Med. Chem. Lett. 2005, 15, 1915. (b) Hussain, M.A.; Cronin, T.H.; Scriabine, A.J. Med. Chem. 1968, 11, 130. (d) McLaughlin, N.P.; Especially in the field of anticancer drug research, 4-arylaminoquinazoline is an important structural type, which inhibits the growth of tumor cel...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D403/04C07D405/14C07D409/14C07D403/14A61P31/00A61P35/00
CPCC07D403/04C07D403/14C07D405/14C07D409/14
Inventor 彭以元叶兴琳丁秋平邓志红
Owner JIANGXI NORMAL UNIV
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