Preparation method of 4, 5-disubstituted-2-aminothiazole compound

Abstract

The invention discloses a preparation method of a 4, 5-disubstituted-2-aminothiazole compound. The preparation method sequentially includes following steps: 1), reacting a nitro epoxy compound, a hydrogen cyanamide water solution of 50% in mass concentration and sulfide in a solvent at room temperature; 2), concentrating reaction liquid obtained in the step 1) to remove the solvent, cooling to room temperature, using water and ethyl acetate to extract, and subjecting an obtained organic layer to washing, drying and concentrating by a rotary evaporator; 3), performing silica gel column chromatography on concentrate obtained in the step 2) to obtain the 4, 5-disubstituted-2-aminothiazole compound. A method which is simple and easy to implement is provided for efficiently synthesizing the 4, 5-disubstituted-2-aminothiazole compound.

Description

technical field

[0001] The invention belongs to a synthesis method of a compound, and mainly relates to a preparation method of a 4,5-disubstituted-2-aminothiazole compound. Background technique

[0002] Thiazole compounds are an important class of heterocyclic compounds, which play an important role in pharmaceutical research. In particular, 2-aminothiazole compounds have a wide range of applications in drug discovery and development, such as the synthesis of anticancer, antitumor, antibacterial, and anti-inflammatory drugs.

[0003] Due to the wide application of 2-aminothiazole group, its synthetic method has been widely concerned. The most important synthetic method is the Hantzsch ring condensation method (Hantzsch, A.; Weber, J.H.Chemische Berichte.1887,20,3118), which uses α-halogenated ketone / aldehyde or α-toluenesulfonyl ketone / aldehyde with Thiourea is used as a raw material and condensed to obtain 2-aminothiazole compound (Formula 1).

[0004]

[0005] Formu...

Examples

Embodiment 1-1

[0052] Example 1-1, 4-methyl-5-(4-bromophenyl)-2-aminothiazole (m1)

[0053]Add 210.1 mg (2.5 mmol) of 50% aqueous cyanamide solution and 480.4 mg (1 mmol) of sodium sulfide nonahydrate into the reaction flask, then add 2.0 mL of n-propanol, 2-methyl-2-nitro-3-( 128.5 mg (0.5 mmol) of 4-bromophenyl) oxirane. After the addition, the reaction was stirred at room temperature for 8 hours, and the reaction was detected by TLC (dichloromethane:methanol=20:1 volume ratio). At this time, the TLC detection reaction result was that 2-methyl-2-nitro-3-(4-bromophenyl)oxirane disappeared, indicating that the reaction had ended.

[0054] After the reaction was finished, concentrate to remove n-propanol, cool to room temperature, add 60mL of water, extract the reaction solution three times with 3×20mL ethyl acetate, wash the organic layer (at the upper layer) three times with 3×30mL saturated brine, and then wash with Anhydrous sodium sulfate (2.0g) was dried for 30 minutes, concentrated by...

Embodiment 1

[0062] Embodiment 1-2, sodium sulfide nonahydrate is changed into sodium hydrosulfide, and the molar weight is constant; all the other are the same as in embodiment 1. 73.7 mg of the product 4-methyl-5-(4-bromophenyl)-2-aminothiazole was obtained as a white solid, with a yield of 55%.

Embodiment 1-3

[0063] Embodiment 1-3, replace n-propanol with methanol, the volume is constant; all the other are the same as embodiment 1. 96.5 mg of the product 4-methyl-5-(4-bromophenyl)-2-aminothiazole was obtained as a white solid, with a yield of 72%.

technical field

[0001] The invention belongs to a synthesis method of a compound, and mainly relates to a preparation method of a 4,5-disubstituted-2-aminothiazole compound. Background technique

[0002] Thiazole compounds are an important class of heterocyclic compounds, which play an important role in pharmaceutical research. In particular, 2-aminothiazole compounds have a wide range of applications in drug discovery and development, such as the synthesis of anticancer, antitumor, antibacterial, and anti-inflammatory drugs.

[0003] Due to the wide application of 2-aminothiazole group, its synthetic method has been widely concerned. The most important synthetic method is the Hantzsch ring condensation method (Hantzsch, A.; Weber, J.H.Chemische Berichte.1887,20,3118), which uses α-halogenated ketone / aldehyde or α-toluenesulfonyl ketone / aldehyde with Thiourea is used as a raw material and condensed to obtain 2-aminothiazole compound (Formula 1).

[0004]

[0005] Formu...

Examples

Embodiment 1-1

[0052] Example 1-1, 4-methyl-5-(4-bromophenyl)-2-aminothiazole (m1)

[0053]Add 210.1 mg (2.5 mmol) of 50% aqueous cyanamide solution and 480.4 mg (1 mmol) of sodium sulfide nonahydrate into the reaction flask, then add 2.0 mL of n-propanol, 2-methyl-2-nitro-3-( 128.5 mg (0.5 mmol) of 4-bromophenyl) oxirane. After the addition, the reaction was stirred at room temperature for 8 hours, and the reaction was detected by TLC (dichloromethane:methanol=20:1 volume ratio). At this time, the TLC detection reaction result was that 2-methyl-2-nitro-3-(4-bromophenyl)oxirane disappeared, indicating that the reaction had ended.

[0054] After the reaction was finished, concentrate to remove n-propanol, cool to room temperature, add 60mL of water, extract the reaction solution three times with 3×20mL ethyl acetate, wash the organic layer (at the upper layer) three times with 3×30mL saturated brine, and then wash with Anhydrous sodium sulfate (2.0g) was dried for 30 minutes, concentrated by...

Embodiment 1

[0062] Embodiment 1-2, sodium sulfide nonahydrate is changed into sodium hydrosulfide, and the molar weight is constant; all the other are the same as in embodiment 1. 73.7 mg of the product 4-methyl-5-(4-bromophenyl)-2-aminothiazole was obtained as a white solid, with a yield of 55%.

Embodiment 1-3

[0063] Embodiment 1-3, replace n-propanol with methanol, the volume is constant; all the other are the same as embodiment 1. 96.5 mg of the product 4-methyl-5-(4-bromophenyl)-2-aminothiazole was obtained as a white solid, with a yield of 72%.

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