thiopropazate

Originator

Dartal,Searle,US,1957

Definition

ChEBI: A phenothiazine derivative in which 10H-phenothiazine has a chloro subsitituent at the 2-position and a 3-[4-(2-acetoxyethyl)piperazin-1-yl]propyl group at N-10.

Manufacturing Process

A mixture of 155 parts of 2-chloro-10-(γ-chloropropyl)phenothiazine, 75 parts of sodium iodide, 216 parts of piperazine and 2,000 parts of butanone is refluxed for 8 hours, concentrated and extracted with dilute hydrochloric acid. The extract is rendered alkaline by addition of dilute potassium carbonate and extracted with ether. This ether extract is washed with water, dried over anhydrous potassium carbonate, filtered and evaporated. Vacuum distillation at 0.1 mm pressure yields 2-chloro-10-(γ-piperazinopropyl)phenothiazine at about 214°C to 218°C.
A mixture of 50 parts of the distillate, 25.6 parts of β-bromoethyl acetate, 10.7 parts of potassium carbonate and 400 parts of toluene is stirred at reflux temperature for 16 hours. The mixture is heated with water. The organic layer is separated, washed with water and extracted with dilute hydrochloric acid. The resulting extract is washed with benzene, rendered alkaline and extracted with benzene. The resulting benzene solution is dried over anhydrous potassium carbonate, filtered and concentrated. The residue is dissolved in 300 parts of ethanol and treated with 2.2 equivalents of a 25% solution of anhydrous hydrochloric acid in 2-propanol. The resulting crystals are recrystallized from 400 parts of ethanol and 10 parts of water. The dihydrochloride of N-(β-acetoxyethyl)-N'-[γ-(2'-chloro-10'- phenothiazine)propyl]piperazine melts unsharply at about 200°C to 230°C.

brand name

Thiopropazate is INN and BAN.

Therapeutic Function

Antipsychotic