The preparation method of benzodiazepine compound

Abstract

The invention relates to a preparation method of a benzodiazepine compound, which comprises the following steps: reacting amino functionalized ionic liquid, phenylpropyl aldehyde, Boc-anthranilic acid and cyclohexyl isonitrile to obtain an ionic-liquid-loaded Ugi product; reacting the ionic-liquid-loaded Ugi product under the catalytic action of hydrogen chloride gas to obtain a benzodiazepine compound of which the side chain is modified by Ugi reaction; and carrying out rotary evaporation on the reaction liquid, and washing out residues with anhydrous aether to obtain the required benzodiazepine compound. Compared with the existing preparation method, the preparation method provided by the invention shortens the reaction procedures and enhances the reaction efficiency; and the synthesis method is simple and efficient, and has wide application prospects.

Description

technical field

[0001] The invention relates to a preparation method of a benzodiazepine compound, in particular to a benzodiazepine compound whose side chain is modified by a Ugi product through the reaction of ionic liquid loading Ugi. Background technique

[0002] Benzodiazepines are a class of compounds with a wide range of biological activities. At present, such compounds are usually synthesized by Ugi reaction, which can not only shorten the synthetic route, improve the reaction efficiency, but also play the role of side chain modification. In 1996, Thomas et al directly synthesized benzodiazepines through Ugi reaction (J.Org.Chem., 1996, 61, 8935-8939). Conventional synthetic benzodiazepines method reaction formula is as follows:

[0003]

[0004] But this multi-component (four components) condensation reaction, in the case of no load, other components in the reaction system are difficult to remove, and finally can only be purified by the method of silica gel col...

Examples

Embodiment 1

[0019] Embodiment 1, the synthesis of N-cyclohexyl-2-(2,5-dioxo-1,4-benzodiazepine)-4-phenylbutanamide

[0020] 0.0286g (0.100mmol) amino functionalized ionic liquid boron tetrafluoride 1-[2-(aminoacetoxy) ethyl]-3-methylimidazolium salt, 0.0160g (0.120mmol) phenylpropanal was added to 50ml In the round bottom flask, pass nitrogen protection, add 10.0ml of anhydrous acetonitrile, add 2.00ml of triethylamine dropwise, stir at room temperature for 30min, cool to 0°C, add 0.0237g (0.100mmol) Boc-anthranilic acid in turn , 0.0109 g (0.100 mmol) cyclohexylisonitrile. After stirring at room temperature for 24 h, the filtrate was evaporated to dryness to obtain the Ugi product supported by ionic liquid, which was washed 3 times with 10.0 ml of anhydrous ether and 3 times with 10.0 ml of toluene.

[0021] After adding 5.00 ml of anhydrous methanol and 0.0142 ml (0.200 mmol) of acetyl chloride into the reaction bottle and stirring at room temperature for 24 h, a benzodiazepine compoun...

technical field

[0001] The invention relates to a preparation method of a benzodiazepine compound, in particular to a benzodiazepine compound whose side chain is modified by a Ugi product through the reaction of ionic liquid loading Ugi. Background technique

[0002] Benzodiazepines are a class of compounds with a wide range of biological activities. At present, such compounds are usually synthesized by Ugi reaction, which can not only shorten the synthetic route, improve the reaction efficiency, but also play the role of side chain modification. In 1996, Thomas et al directly synthesized benzodiazepines through Ugi reaction (J.Org.Chem., 1996, 61, 8935-8939). Conventional synthetic benzodiazepines method reaction formula is as follows:

[0003]

[0004] But this multi-component (four components) condensation reaction, in the case of no load, other components in the reaction system are difficult to remove, and finally can only be purified by the method of silica gel col...

Examples

Embodiment 1

[0019] Embodiment 1, the synthesis of N-cyclohexyl-2-(2,5-dioxo-1,4-benzodiazepine)-4-phenylbutanamide

[0020] 0.0286g (0.100mmol) amino functionalized ionic liquid boron tetrafluoride 1-[2-(aminoacetoxy) ethyl]-3-methylimidazolium salt, 0.0160g (0.120mmol) phenylpropanal was added to 50ml In the round bottom flask, pass nitrogen protection, add 10.0ml of anhydrous acetonitrile, add 2.00ml of triethylamine dropwise, stir at room temperature for 30min, cool to 0°C, add 0.0237g (0.100mmol) Boc-anthranilic acid in turn , 0.0109 g (0.100 mmol) cyclohexylisonitrile. After stirring at room temperature for 24 h, the filtrate was evaporated to dryness to obtain the Ugi product supported by ionic liquid, which was washed 3 times with 10.0 ml of anhydrous ether and 3 times with 10.0 ml of toluene.

[0021] After adding 5.00 ml of anhydrous methanol and 0.0142 ml (0.200 mmol) of acetyl chloride into the reaction bottle and stirring at room temperature for 24 h, a benzodiazepine compoun...

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