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A kind of synthetic method of 5h-1,4-benzodiazepine compound

A technology of benzodiazepine and 5H-1, which is applied in the direction of organic chemistry, can solve problems such as long reaction time, and achieve the effect of obvious advantages, low requirements for reaction conditions, and wide application range

Active Publication Date: 2021-11-23
YANGZHOU UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Known methods include the cyclocondensation reaction of o-aminobenzylamine and benzil, the cyclooxidation reaction of o-aminobenzylamine and 1,2-disubstituted acetylene compounds, etc., but there are still many shortcomings in these methods, either need Harsh conditions such as high temperature and excess oxidant, either require a long reaction time, or require multi-step reactions to obtain the target compound

Method used

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  • A kind of synthetic method of 5h-1,4-benzodiazepine compound
  • A kind of synthetic method of 5h-1,4-benzodiazepine compound
  • A kind of synthetic method of 5h-1,4-benzodiazepine compound

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0020] Preparation of 5-H-1,4-benzodiazepine from 2-aminobenzylamine and 2-hydroxy-2-phenylacetophenone

[0021]

[0022] Add 2-aminobenzylamine (91.6mg, 0.75mmol), 2-hydroxy-2-phenylacetophenone (106.1mg, 0.5mmol), AcOH (0.25mL) to the 100mL high-pressure sealed tube in sequence, and add An air balloon, and then heated and stirred at 80° C. for 24 hours. After the completion of the reaction was monitored by TLC or GC-MS, the product was separated and purified by column chromatography, and the separation yield was 95%. 1 H NMR (400MHz, CDCl 3 ):δ7.84-7.81(m,2H),7.54(t,J=7.8Hz,3H),7.41(dd,J=7.4,2.9Hz,2H),7.36(d,J=5.0Hz,3H) ,7.26-7.20(m,4H),4.88(d,J=10.6Hz,1H),3.99(d,J=10.6Hz,1H). 13 C NMR (100MHz, CDCl 3 ): δ164.4, 160.5, 147.4, 137.6, 137.2, 130.6, 130.5, 129.9, 128.5, 128.5, 128.4, 128.3, 128.3, 127.9, 126.8, 125.6, 54.6. HRMS (ESI): m / z calcd for C 21 h 16 N 2 (M+H):297.1347;found:297.1391.This compound was known:Randles K.R.;Storr R.C.J.Chem.Soc.Chem.Commun.1984,22...

Embodiment 2

[0024] Preparation of 2,3-di-p-tolyl-5H-1,4-benzodiazepine from 2-aminobenzylamine and 2-hydroxy-1,2-di-p-tolyl-1-one

[0025]

[0026] 2-aminobenzylamine (91.6mg, 0.75mmol), 2-hydroxy-1,2-di-p-tolyl-1-one (120.1mg, 0.5mmol), AcOH (0.25mL), Add an air balloon to the tube sealing port, and then heat and stir at 80°C for 24 hours. After the reaction is complete as monitored by TLC or GC-MS, the product is separated and purified by column chromatography, and the separation yield is 96%. 1 HNMR (400MHz, CDCl 3 ): δ7.75(d, J=8.2Hz, 2H), 7.54(d, J=7.8Hz, 1H), 7.46-7.37(m, 4H), 7.22(d, J=7.4Hz, 1H), 7.16 (d,J=8.0Hz,2H),7.03(d,J=8.1Hz,2H),4.84(d,J=10.6Hz,1H),3.98(d,J=10.6Hz,1H),2.34(s ,3H),2.26(s,4H). 13 C NMR (100MHz, CDCl 3 ): δ164.6, 160.3, 147.6, 140.9, 139.9, 135.1, 134.7, 130.8, 129.2, 129.0, 128.4, 128.4, 128.4, 128.25, 127.86, 126.44, 125.52, 54.62, 21.50, 21.3 calcd for C 23 h 20 N 2 (M+H):325.1699;found:325.1714.This compound was known:cas:2111154-09-5.

Embodiment 3

[0028] Preparation of 2,3-di-m-tolyl-5H-1,4-benzodiazepine from 2-aminobenzylamine and 2-hydroxy-1,2-di-m-tolyl-1-one

[0029]

[0030] 2-aminobenzylamine (91.6mg, 0.75mmol), 2-hydroxy-1,2-di-m-tolyl-1-one (120.1mg, 0.5mmol), AcOH (0.25mL), Add an air balloon to the tube sealing port, then heat and stir at 80°C for 24 hours. After the reaction is complete as monitored by TLC or GC-MS, the product is separated and purified by column chromatography, and the separation yield is 88%. 1 HNMR (400MHz, CDCl 3 ): δ7.79(s,1H),7.55(d,J=7.8Hz,1H),7.52–7.46(m,2H),7.40(t,J=9.1Hz,2H),7.22(dd,J= 14.2,6.5Hz,4H),7.10–7.05(m,2H),4.86(d,J=10.6Hz,1H),3.98(d,J=10.6Hz,1H),2.37(s,3H),2.27( s,3H). 13 C NMR (100MHz, CDCl 3 ): δ164.9, 160.7, 147.4, 138.3, 138.1, 137.7, 137.3, 131.4, 130.7, 130.6, 128.4, 128.3, 128.2, 128.2, 128.1, 127.8, 126.6, 126.1, 125.8, 125.5, 1.5 ESI): m / z calcd for C 23 h 20 N 2 (M+H):325.1699;found:325.1715.This compound was known:cas:2111154-09-5.

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Abstract

The invention discloses a synthesis method of a 5H-1,4-benzodiazepine compound. The invention discloses a method for preparing 5H-1,4-benzodiazepine heterocyclic compound through one-step series reaction of an o-aminobenzylamine compound and 2-hydroxy-2-phenylacetophenone by using air as an oxidant under the action of an acid. The method does not need to use expensive transition metal catalysts and ligands, but uses solvent acid as a promoter, without other metal catalysts, and without a large amount of oxidant, so the product has no transition metal residues and is suitable as a precursor for drug preparation. The method conditions It is simple, easy to operate, has low requirements on equipment, and can use air as an economical, safe and green oxidant, solvent acid as an accelerator, and the only by-product is water, with high atomic economy.

Description

technical field [0001] The invention relates to the field of chemical synthesis, in particular to a method for preparing 5H-1,4- Green synthesis method of benzodiazepine compounds. Background technique [0002] Nitrogen-containing seven-membered heterocyclic compounds represented by benzodiazepines, as important structures and components of natural products and biologically active substances, have many pharmacological and biological activities, such as anti-anxiety, anti-depressant Anticonvulsants, sedatives, analgesics, etc. Therefore, the synthesis of 1,4-benzodiazepine compounds has also aroused widespread interest among synthetic and medicinal chemists. There have been many reports on the synthesis methods of 1,5-benzodiazepine compounds, but few reports on the synthesis methods of 5H-1,4-benzodiazepine compounds. Known methods include the cyclocondensation reaction of o-aminobenzylamine and benzil, the cyclooxidation reaction of o-aminobenzylamine and 1,2-disubstitut...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D243/14C07D409/14C07D243/08
CPCC07D243/08C07D243/14C07D409/14
Inventor 徐清王琦
Owner YANGZHOU UNIV