FLURAZEPAM DIHYDROCHLORIDE

Originator

Dalmane, Roche,US,1970

The Uses of FLURAZEPAM DIHYDROCHLORIDE

Flurazepam is used as an sedative, hypnotic. This is a controlled substance (depressant).

Definition

ChEBI: Flurazepam hydrochloride is a benzodiazepine.

Manufacturing Process

13 grams of 5-(2-fluorophenyl)-7-chloro-2,3-dihydro-1H-1,4benzodiazepinone-(2) were dissolved in 100 ml of N,N-dimethylformamide andtreated with 10.3 ml of a solution of sodium methoxide in methanol containing 54 mmol or 2.95 grams of sodium methoxide. The resulting solution was stirred at about 20°C for 1 hour and then cooled in an ice-salt mixture to 0°C. A solution of diethylamino-ethyl chloride was prepared by dissolving 13.8 grams of diethylamino-ethyl chloride hydrochloride in cold dilute sodium hydroxide solution and extracting the base four times with 50 ml of toluene each time. The toluene extracts were combined, dried over anhydrous sodium sulfate, filtered and added to the reaction mixture.
The mixture was allowed to stand for 70 hours and then concentrated to a small volume under reduced pressure. The residue was dissolved in 100 ml of methylene chloride, washed with 75 ml of water, three times with 50 ml of saturated brine solution each time and filtered over neutral alumina (grade 1). The filtrate was evaporated to dryness and the resulting colorless oil taken up in ether, which was then saturated with hydrogen chloride. The pale yellow precipitate was filtered off and recrystallized from methanol/ether yielding 1[2-(diethylamino)ethyl]-5-(2-fluorophenyl)-7-chloro-2,3-dihydro-1H-1,4benzodiazepinone-(2) dihydrochloride as pale yellow rods melting at 190° to 220°C with decomposition, (from British Patent 1,040,548).

Therapeutic Function

Hypnotic

General Description

Odorless off-white to yellow crystalline powder.

General Description

Flurazepamhydrochloride, 7-chloro-1-[2-(diethylamino)ethyl]-5-(2-fluorophenyl)-1, 3-dihydro-2H-1, 4-benzodiazepine-2-onedihydrochloride (Dalmane), is notable as a benzodiazepinemarketed almost exclusively for use in insomnia.Metabolism of the dialkylaminoalkyl side chain isextensive. A major metabolite is N¹-dealkyl flurazepam,which has a very long half-life and persists for severaldays after administration. Consequently, it produces cumulativeclinical effects and side effects (e.g., excessivesedation) and residual pharmacologic activity, even afterdiscontinuation.

Air & Water Reactions

Water soluble.

Fire Hazard

Flash point data for FLURAZEPAM DIHYDROCHLORIDE are not available. FLURAZEPAM DIHYDROCHLORIDE is probably combustible.