Benzquinamid

Originator

Emete-Con,Roerig,US,1974

The Uses of Benzquinamid

Anti-emetic.

Definition

ChEBI: Benzquinamide is a monocarboxylic acid amide. It has a role as an antiemetic, a sedative, a H1-receptor antagonist, a muscarinic antagonist and an antipsychotic agent.

Manufacturing Process

According to US Patent 3,055,894, a solution consisting of 3.4 grams (0.01mol) of 2-oxo-3-carboethoxy-9,10-dimethoxy-1,2,3,4,6,7-hexahydro- 11b-H-benzopyridocoline and 0.8 grams (0.011 mol) of freshly distilled diethylamine dissolved in 50 ml of xylene was refluxed under a nitrogen atmosphere for 24 hours. After cooling to room temperature, the reaction mixture was successively extracted with four 100 ml portions of water. The aqueous phase was then discarded and the xylene layer was passed through a paper filter containing a bed of sodium sulfate and activated charcoal. The resulting filtrate was then heated under reduced pressure (65 mm Hg) via a water bath at 50°C in order to remove the xylene solvent, and the residual oil so obtained was cooled to approximately 5°C and held at that point until a semisolid formed (required approximately 16 hours). Recrystallization of the semisolid from aqueous ethanol in the presence of activated charcoal afforded light yellow crystals of 2-oxo-3-(N,N-diethylcarboxamido)-9,10-dimethoxy- 1,2,3,4,6,7-hexahydro-11b-H-benzopyridocoline, MP 150°-152°C.
Then, as described in US Patent 3,053,845, one hundred grams (0.278 mol) of 2-oxo-3-(N,N-diethylcarboxamido)-9,10-dimethoxy-1,2,3,4,6,7-hexahydro- 11b-H-benzopyridocoline was dissolved in 1,500 ml of hot methanol and the resulting solution was allowed to cool to room temperature. After removal of all the dissolved oxygen therein by saturation of the solution with dry nitrogen, 5.0 grams of Adams' platinum oxide catalyst was introduced into the system in one portion while still maintaining same under a nitrogen atmosphere.
The reaction flask and its contents were then shaken at room temperature under slightly greater than one atmosphere of hydrogen pressure until the total hydrogen uptake was completed. Dissolved hydrogen gas was then removed from the reaction solution by saturation of same with respect to dry nitrogen, while the platinum black was removed by means of gravity filtration. Concentration of the resulting filtrate under reduced pressure on a steam bath then afforded a nearly quantitative yield of 2-hydroxy-3-(N,Ndiethyicarboxamido)-9,10-dimethoxy-1,2,3,4,6,7-hexahydro-11b-Hbenzopyridocoline as a yellow crystalline solid (mixture of the axial and equatorial forms).
A mixture consisting of 2 grams of 2-hydroxy-3-(N,N-diethylcarboxamido)- 9,10-dimethoxy-1,2,3,4,6,7-hexahydro-11 b-H-benzopyridocoline (OH-axial) hydrochloride (prepared by treating the base with hydrogen chloride gas in absolute ether) dissolved in 7 ml of acetic anhydride containing 3 ml of pyridine was heated at 100°C for 2 hours under a nitrogen atmosphere. At the end of this period, a crystalline precipitate had formed and the resultant mixture was subsequently diluted with an equal volume of diethyl ether and filtered.
The crystalline hydrochloride salt so obtained, i.e., the solid material collected on the filter funnel, was then converted to the corresponding free base by distribution in 10 ml of a benzene-aqueous 5% sodium carbonate system. The product recovered from the benzene extracts was then recrystallized from diisopropyl ether to afford 1.46 grams of 2-acetoxy-3-(N,Ndiethylcarboxamido)-9,10-dimethoxy-1,2,3,4,6,7-hexahydro-11b-Hbenzopyridocoline (CH3COO-axial), MP 130°-131.5°C.

brand name

Emete-con (Roerig); Quantril (Roerig).

Therapeutic Function

Tranquilizer, Antinauseant