triflupromazine

Manufacturing Process

Approximately 3.8 grams of sodamide is freshly prepared from 2.25 grams of sodium, 90 grams of liquid ammonia and a catalytic trace of ferric nitrate. The ammonia is allowed to evaporate. A solution of 19.1 grams of 2-trifluoromethylphenothiazine (prepared by the Bernthsen thionation of 3- trifluoromethyldiphenylamine) in 160 ml of dry benzene is added to the reaction flask followed by 18 grams of 3-chloro-1-dimethylaminopropane. The reaction mixture is heated at reflux for 20 hours. After washing the cooled mixture with 130 ml of water, the organic layer is extracted with several portions of dilute hydrochloric acid. The acid extracts are combined and neutralized with ammonium hydroxide solution. The oily free base is extracted into benzene and purified by distillation to give 19.6 grams of 10-(3'- dimethylaminopropyl)-2-trifluoromethylphenothiazine, boiling point 177° to 181°C at 1 mm. The free base (7 grams) is converted to the hydrochloride salt by reacting an alcoholic solution of the base with hydrogen chloride gas. Evaporation of the volatiles in vacuo leaves an amorphous solid which is recrystallized from ethanol/ether to pink crystals, MP 173° to 174°C, the hydrochloride salt of the free base prepared above.

Therapeutic Function

Tranquilizer

Safety Profile

Poison by ingestion, intravenous, and intraperitoneal routes. Experimental reproductive effects. Mutation data reported. When heated to decomposition it emits very toxic fumes of F-, NOx, and SOx. See also FLUORIDES.

Synthesis

Triflupromazine, 2-trifluoromethyl-10-(3-dimethylaminopropyl) phenothiazine (6.1.3), also is synthesized by the alkylation of 2-trifluoromethylphenothiazine using 3-dimethylaminopropylchloride in the presence of sodium amide [7–12].

Definition

ChEBI: A member of the class of phenothiazines that is 10H-phenothiazine having a trifluoromethyl subsitituent at the 2-position and a 3-(dimethylamino)propyl group at the N-10 position.

Brand name

Vesprin (Apothecon).