PROCESS OF MAKING BENZODIAZOCINES

摘要

A process or making benzodiazocine derivatives of the formula I wherein R1 is hydrogen, lower alkyl which may be a straight or branched chain with 1 to 6 carbon atoms and may be substituted by halogen, lower alkoxy with at most 4 carbon atoms or phenyl radical, or a cyclic alkyl with 3 to 6 carbon atoms, R2 is a halo, hydroxyl, acetoxy or benzoxy radical, R3 is phenyl or phenyl substituted with one to three member of the group of halogen, alkyl, alkylthio, alkoxy, the alkyl, alkylthio or alkoxy moities of which have at most 4 carbon atoms, or phenyl substituted with a nitro or trifluoromethyl alone or together with one or two of the above substituent, or an ethylenedioxyphenyl, R4 and R5 are each of a radical of the group consisting of hydrogen, halogen, alkyl, alkoxy or alkylthio, the alkyl, alkoxy or alkylthio moities of which have at most 4 carbon atoms, or a trifluoromethyl radical, or together an ethylenedioxy radical; or a pharmaceutically acceptable acid addition salt of said benzodiazocine derivatives of the formula I, said process comprising heating an acyldiamine having the formula II in which R is a hydroxy, acetoxy, or benzoxy radical, and R1, R3, R4 and R5 have the same significance as before, with a phosphorus oxyhalide in an inert solvent at a temperature between 50 and 100.degree.C, when the R radical is a hydroxyl radical for making a benzodiazocine derivative of the formula I wherein R2 is halogen, and at a temperature between 50 and 150.degree.C when the R radical is an acetoxy or benzoxy radical for making a benzodiazocine derivative of the formula I wherein R2 is acetoxy or benzoxy, and hydrolyzing the benzodiazocine derivative wherein R2 is acetoxy or benzoxy to a benzodiazocine derivative of the formula I wherein R2 is hydroxy, treating the formula I compound obtained with an acid to convert it into a pharmaceutically compatible acid addition salt thereof, or liberating a base of formula I from its acid addition salt. The invention also embraces benzodiazocine compounds as shown in above formula I whenever made by the above process.