Open AccessNew technology to obtain 1-methyl-5-pnenyl-7-chloro- 1,3-dihydro-2H-[1,4]-benzodiazepine-2-one
Author(s) -
Natalya I. Lyukshenko,
Roman G. Nikitin,
Yury V. Morozhenko
Publication year - 2019
Publication title -
butlerovskie soobŝeniâ
Language(s) - English
Resource type - Journals
ISSN - 2074-0212
DOI - 10.37952/roi-jbc-01/19-60-10-24
Subject(s) - benzodiazepine , ring (chemistry) , chemistry , diazepine , halogen , benzene , nitro , phenyl group , medicinal chemistry , combinatorial chemistry , stereochemistry , organic chemistry , alkyl , receptor , biochemistry
At present, benzodiazepine derivatives being used widely, they continue to occupy a leading position among the drugs of the anxiolytic group. Most anxiolytics of the benzodiazepine structure are derivatives of 1,4-benzodiazepine. The basis of the chemical benzodiazepine structure consists of a benzene ring connected to a seven-membered heterocyclic ring containing two nitrogen atoms (diazepine) at positions 1 and 4. All the benzodiazepine derivatives used in the clinic also have a second benzene ring attached to carbon. The presence of a halogen or a nitro group is essential to display its activity. Diazepam (1-methyl-5-phenyl-7-chloro-1,3-dihydro-2H- [1,4] benzodiazepin-2-one) is in the list of necessary and important medicinal products. The urgent issue is the development of a new method to synthesize 1-methyl-5-phenyl-7-chloro-1,3-dihydro-2H-[1,4]-benzodiazepines-2-one that would allow producing the drug in the required quantities and for mass consumption. The search for possible effective ways of synthesizing 1-methyl-5-phenyl-7-chlorine-1,3-dihydro-2H-[1,4]-benzodiazepines-2-one for manufacturing application is of great scientific and practical interest. The purpose of our work is to search for a rational method to synthesize the target product, experimental study of the chemical processes to develop the most optimal methods to produce the product. The technology to produce 1-methyl-5-phenyl-7-chlor-1,3-dihydro-2H-[1,4]-benzodiazepine-2-one on an industrial scale was developed. The synthesis of 2-benzoyl-2',4-dichloro-N-methylacetanilide by condensation of 2-methylamine-5-chlorobenzophenone with chloracetyl chloride in carbon tetrachloride without further treatment of the reaction mass with water and sodium carbonate was developed. The highest yield of 1-methyl-5-phenyl-7-chlorine-1,3-dihydro-2H-[1,4]-benzodiazepines-2-one was shown to be obtained if the cyclization reaction is carried out in isopropyl alcohol. The reaction mixture composition in interaction of 2-benzoyl- 2',4 -dichloro-N-methylacetanilide with urotropin plays the defining role in the formation of the target product.