A kind of trifluoromethylated aniline compound and application thereof

Abstract

The present invention provides a trifluoromethylated aniline compound represented by formula (I), its preparation method and application. In the present invention, compounds such as aminoglutethimide are modified by trifluoromethylation, and the operation process is simple, and the sources of raw materials are commercially available; and after modification, the anti-tumor activity, especially the anti-cervical cancer activity, is significantly improved, especially the compound ( The antitumor activity of Ia) is more than double that of aminoglutethimide. Compared with the previous aniline drug modification method, the trifluoromethylation modification method adopted in the present invention is more direct, efficient and fast.

Description

[0001] (1) Technical field

[0002] The invention belongs to the technical field of organic chemistry, and in particular relates to a trifluoromethylated aniline compound and an application thereof.

[0003] (2) Background technology

[0004] Tumor is a new organism formed by the body under the action of various tumorigenic factors, and the cells of local tissues lose their normal regulation of their growth at the gene level, resulting in abnormal proliferation and differentiation. Tumor has the characteristics of fast growth, easy metastasis, difficult to cure, and high lethality. It is a major disease that seriously threatens the safety of human life. There are many anti-tumor drugs, and aminoglutethimide is one of them. Aminoglutethimide can inhibit the production of estrogen by blocking aromatase, thereby reducing the promotion effect of estrogen on breast cancer and inhibiting tumor growth. Bacteria are both useful and harmful to the environment, humans and animals. Som...

Examples

Embodiment 1

[0036]

[0037] Add 46.4mg (0.2mmol) of aminoglutethimide to a mixed solvent of 2ml of DMF and water (1ml:1ml), add 126.4mg (0.4mmol) of 1-(trifluoromethyl)-1,2-benzene Iodosyl-3(1H)-one, 13.3mg (0.04mmol) fluorescein, reacted under blue light irradiation at room temperature for 6 hours, after the reaction, extraction operation: 1. Add saturated NaCl aqueous solution and acetic acid to the reaction solution in sequence Ethyl was extracted twice. 2. Add 50 mL of saturated NaCl aqueous solution and 30 mL of ethyl acetate for the first time to perform one extraction. 3. After the first extraction, collect the organic layer, take the aqueous phase layer and add 20 ml of ethyl acetate for the second extraction. After the extraction was completed, the organic layer was dried over anhydrous sodium sulfate, filtered, and the solvent was removed by rotary evaporation at room temperature to obtain the crude compound. The crude compound was subjected to silica gel column chromatograph...

Embodiment 2

[0039] In addition to changing the mass and moles of 1-(trifluoromethyl)-1,2-phenyliodyl-3(1H)-one to 63.2 mg (0.2 mmol), the mass and moles of fluorescein to 0.664 mg (0.002mmol), other operation is constant, and operating procedure is with embodiment 1, obtains the compound pure product 12mg shown in formula (Ia), and reaction yield is 20%.

Embodiment 3

[0041] In addition to changing the mass and moles of 1-(trifluoromethyl)-1,2-phenyliodyl-3(1H)-one to 189.6 mg (0.6 mmol), the mass and moles of fluorescein to 33.2 mg (0.1mmol), other operation is constant, and operating procedure is with embodiment 1, obtains the compound pure product 15mg shown in formula (Ia), and reaction yield is 25%.

[0001] (1) Technical field

[0002] The invention belongs to the technical field of organic chemistry, and in particular relates to a trifluoromethylated aniline compound and an application thereof.

[0003] (2) Background technology

[0004] Tumor is a new organism formed by the body under the action of various tumorigenic factors, and the cells of local tissues lose their normal regulation of their growth at the gene level, resulting in abnormal proliferation and differentiation. Tumor has the characteristics of fast growth, easy metastasis, difficult to cure, and high lethality. It is a major disease that seriously threatens the safety of human life. There are many anti-tumor drugs, and aminoglutethimide is one of them. Aminoglutethimide can inhibit the production of estrogen by blocking aromatase, thereby reducing the promotion effect of estrogen on breast cancer and inhibiting tumor growth. Bacteria are both useful and harmful to the environment, humans and animals. Som...

Examples

Embodiment 1

[0036]

[0037] Add 46.4mg (0.2mmol) of aminoglutethimide to a mixed solvent of 2ml of DMF and water (1ml:1ml), add 126.4mg (0.4mmol) of 1-(trifluoromethyl)-1,2-benzene Iodosyl-3(1H)-one, 13.3mg (0.04mmol) fluorescein, reacted under blue light irradiation at room temperature for 6 hours, after the reaction, extraction operation: 1. Add saturated NaCl aqueous solution and acetic acid to the reaction solution in sequence Ethyl was extracted twice. 2. Add 50 mL of saturated NaCl aqueous solution and 30 mL of ethyl acetate for the first time to perform one extraction. 3. After the first extraction, collect the organic layer, take the aqueous phase layer and add 20 ml of ethyl acetate for the second extraction. After the extraction was completed, the organic layer was dried over anhydrous sodium sulfate, filtered, and the solvent was removed by rotary evaporation at room temperature to obtain the crude compound. The crude compound was subjected to silica gel column chromatograph...

Embodiment 2

[0039] In addition to changing the mass and moles of 1-(trifluoromethyl)-1,2-phenyliodyl-3(1H)-one to 63.2 mg (0.2 mmol), the mass and moles of fluorescein to 0.664 mg (0.002mmol), other operation is constant, and operating procedure is with embodiment 1, obtains the compound pure product 12mg shown in formula (Ia), and reaction yield is 20%.

Embodiment 3

[0041] In addition to changing the mass and moles of 1-(trifluoromethyl)-1,2-phenyliodyl-3(1H)-one to 189.6 mg (0.6 mmol), the mass and moles of fluorescein to 33.2 mg (0.1mmol), other operation is constant, and operating procedure is with embodiment 1, obtains the compound pure product 15mg shown in formula (Ia), and reaction yield is 25%.

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