Quinazoline derivative and preparation method and application thereof

A derivative, quinazoline technology, applied in drug combinations, antineoplastic drugs, organic chemistry, etc., to achieve the effects of less by-products, high product purity, and wide substrate applicability

Active Publication Date: 2018-12-28
JIANGXI NORMAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0009] After literature research, we found that there is no very eff

Method used

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  • Quinazoline derivative and preparation method and application thereof
  • Quinazoline derivative and preparation method and application thereof
  • Quinazoline derivative and preparation method and application thereof

Examples

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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 and a preparation method and application thereof. The derivative has the structure represented as the formula (1). The preparation method comprises the steps that under the alkaline condition and the existence of a ligand and at least one catalyst of trifluoroacetic acid palladium, tetrakis (triphenylphosphine) palladium, triphenyl phosphine palladium dichloride, tris (dibenzalacetone) dipalladium and palladium acetate, a compound represented as the formula (I) reacts with a compound represented asthe formula (II), and the ligand is 2-dicyclohexylphosphino-2',6'-diMethoxybiphenyl. The quinazoline derivative has excellent antimicrobial activity and antineoplastic activity. The preparation methodis high in yield, wide in substrate adaptability, mild in reaction conditions, simple in operation, low in cost, few in by-products, high in product purity and applicable to large-scale preparation and has a good application prospect.

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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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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