Verfahren zur Herstellung von neuen N-heterocyclischen Verbindungen

摘要

Novel pyrido[2,1 -c][1,4]benzodiazepine - 12-ones, having valuable pharmacological properties and analgesic, tranquillizing and/or anaesthetic effects, of the general formula and pharmaceutically acceptable acid addition salts, quaternary ammonium compounds and N-oxides thereof, wherein R1 and R2 each stand for hydrogen, halogen (particularly, chlorine, bromine or iodine), trifluoromethyl, lower alkyl, lower alkoxy or methylenedioxy when R1 and R2 are taken together and attached to adjacent carbon atoms on the benzene ring; and R3 represents an alkyl, alkenyl, carbonyl-alkyl, carbo (lower) alkoxy-alkyl, lower alkoxy-alkyl, di (lower) alkylaminoalkyl, phenyl, phenyl (lower) alkyl, phenyl (lower) alkylene or cycloalkyl radical, are prepared by reacting in the presence of an acid-binding agent and in an inert solvent the corresponding 1,2,3,11,12,-12a -hexahydro(4H, 6H)pyrido[2,1-c][1,4]benzodiazepine-12-one of the general formula with a halogenide or sulphate of an alcohol of the general formula R3-OH (III) and optionally converting the final product to a pharmaceutically acceptable acid addition salt, quaternary ammonium compound or N-oxide thereof. Pyrido[2,1-c][1,4]benzodiazepine-12-ones of the second general formula are prepared by reacting lower alkyl pipecolinates and appropriately substituted o-nitrobenzyl halides in the presence of an excess of an acid binding agent and in an inert solvent, reducing the resulting N-(o-nitrobenzyl)pipecolinates with hydrogen in the presence of Raney-nickel and simultaneously saponifying and condensing the resulting N-(o-aminobenzyl)pipecolinates to the desired pyridobenzodiazepine ring system with mineral acids. Ethyl pipecolinate is prepared by converting picolinic acid to its hydrochloride salt, reducing to pipecolinic acid hydrochloride and esterifying with ethanol. 6-Nitroveratryl chloride is prepared by reducing 6-nitro-veratraldehyde with t.-butylamine borane and reacting the resulting 6-nitroveratryl alcohol with phosphorus pentachloride.