NEW PRODUCTION METHOD OF 8-CHLORO-6-(2-FLUOROPHENYL)-1-METHYL-4H-IMIDAZO(1,5A)(1,4)-BENZODIAZEPINE(MIDAZOLAM) AND THE INTERMEDIATE USED IN THE SAME

摘要

PROBLEM TO BE SOLVED: To inexpensively obtain the subject compound not requiring a chromatographic purification by suing fluorobenzophenone derivatives as starting materials, carrying out the addition reaction, dehydrocyclization, reduction deprotection, etc. SOLUTION: The compound of formula I is obtained by carrying out the treatment of 2-amino-5-chloro-2'-fluorobenzophenone of formula II with a lower alkyl diethiol, with acetonitrile and with halomalonaldehyde to obtain the compound of formula III (R is CHO), followed by deprotection treatment with hydroxyl amine salt then with a reducing agent. The compound of formula I is useful for a sedative drug, anxiolytic drug, muscle relaxant, anticonvulsant drug. The conventional process contains long and complex chemical reactions and the yield is low and requires a troublesome and a time taking chromatographic isolation but this process does not require a chromatographic purification on each step capable of producing a high purity product.