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Green synthesis method of benzodiazepine compound

A green synthesis and compound technology, applied in the direction of organic chemistry, can solve the problem of low yield and achieve the effect of simple reaction process, wide application prospect and simple post-processing

Active Publication Date: 2021-04-20
SOUTHERN MEDICAL UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] The object of the present invention is to aim at benzodiazepines in the prior art In the preparation of the compound, heating is required, metal catalysts are used, and the yield is low. A kind of benzodiazepine is provided. Green Synthesis of Compounds

Method used

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  • Green synthesis method of benzodiazepine compound
  • Green synthesis method of benzodiazepine compound
  • Green synthesis method of benzodiazepine compound

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0033] Explore the influence of the type of base, the type of solvent in the first step and the type of solvent in the second step on the reaction. The specific process is as follows:

[0034] With 2-aminobenzoic acid hexafluoroisopropanol ester and α-bromoamide as reaction raw materials, the types of alkali and solvent are as shown in Table 1, and the first step reaction was carried out in a 50mL eggplant-shaped bottle for 0.5 hours, and then the first step The reaction solvent was spin-dried using a rotary evaporator, and the reaction solvent in the second step was added to react for 0.5 hours, and an appropriate amount of water was added, and extracted three times with ethyl acetate to collect the organic phase, washed with water, and the solvent was removed by rotary evaporation, and then separated and purified by thin-layer plate. To obtain the product, the thin-layer plate developing agent used is a mixed solvent of petroleum ether:ethyl acetate with a volume ratio of (3-...

Embodiment 2

[0044] React with above-mentioned optimal reaction conditions, change different reaction raw materials, concrete reaction raw materials are as shown in table 2, and wherein the consumption of hexafluoroisopropanol 2-aminobenzoic acid is 0.3mmol, and the consumption of replacement α-bromoamide is 0.3mmol, the amount of cesium carbonate is 0.3mmol, the amount of HFIP is 3mL, react in a 50mL eggplant-shaped bottle for 0.5 hours, remove the solvent by rotary evaporation under reduced pressure, add 2mL of DMF to react for 0.5 hours, add an appropriate amount of water, and use acetic acid The organic phase was collected by ethyl ester extraction three times, washed with water, and then evaporated under reduced pressure to remove the solvent and then separated and purified by thin-layer plate to obtain the product. The thin-layer plate developer used was petroleum ether:acetic acid with a volume ratio of (3-5):1 Mixed solvents of ethyl esters to prepare benzodiazepines with different ...

Embodiment 3

[0053] Embodiment 3: 1 H NMR (400MHz, CDCl 3 )δ7.88(dd,J=9.8,2.9Hz,1H),7.55–7.49(m,2H),7.34–7.29(m,3H),7.14–7.06(m,1H),6.76(dd,J= 8.8,4.5Hz,1H),5.01(s,2H),1.39(s,6H). 13 C NMR (100MHz, CDCl 3 )δ171.8, 162.5 (d, J = 2Hz), 156.9 (d, J = 239Hz), 141.2, 134.2, 129.8, 128.8, 128.3, 122.4 (d, J = 24Hz), 121.6 (d, J = 7Hz), 118.1 , 117.8, 77.7, 57.8, 24.6.

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Abstract

The invention discloses a green synthesis method of a benzodiazepine compound. The structure of the benzodiazepine compound is shown as a formula I; The preparation method comprises the following steps: taking an R1-substituted 2-aminobenzoic acid hexafluoroisopropanol ester compound and an R2-substituted alpha-bromoamide compound as raw materials, taking an alkali as an additive, taking hexafluoroisopropanol as a solvent for reaction, spin-drying the hexafluoroisopropanol, and then adding DMF (Dimethyl Formamide) as a solvent for reaction, so as to generate the benzodiazepine compound as shown in the formula I. According to the method, the substituted 2-aminobenzoic acid hexafluoroisopropanol ester compound and substituted- alpha bromamide are used as the raw materials, the alkali is used as the additive, hexafluoroisopropanol and DMF or DMA are used as solvents in sequence, and the benzodiazepine compound can be obtained through a normal-temperature reaction. The preparation method has the advantages of no need of heating, no need of using a metal catalyst, mild reaction conditions and simple post-treatment process, can obtain the high-yield benzodiazepine product, and is a simple green synthesis method.

Description

technical field [0001] The present invention relates to the technical field of organic synthesis, more specifically, to a kind of benzodiazepine Green synthesis of compounds. Background technique [0002] Heterocyclic derivatives are widely used in many fields, especially organic, pharmaceutical, agricultural chemistry, materials and life sciences, among which benzodiazepines It is an important class of nitrogen heterocyclic compounds. It is known that it has sedative, hypnotic, anxiolytic, antiepileptic, auxiliary anesthesia and muscle relaxation effects. , M.; Ettari, R.; Wen, W.; Wu, A.; Shen, Y.; Niu, L.; ; Minns, A.B.; Kreshak, A.; Dunlay, R.; Castillo, E.; Clark, R.F.; Killeen, J. and Tolia, V.J. Am. Geriatr. Soc. 2019, 67, 1309-1311). Currently, benzodiazepines with novel structures Compounds are still being developed and tested for pharmacological activity. Therefore, research on benzodiazepines The green synthesis and application of compound-like compounds...

Claims

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Application Information

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IPC IPC(8): C07D243/14
CPCY02P20/55
Inventor 唐晓冬陈洁文梁恩吴银容文康梅
Owner SOUTHERN MEDICAL UNIVERSITY