2-[3-[4-(3-chlorophenyl)piperazin-1-yl]propyl]-4,5-diethyl-2,4-dihydro-3H-1,2,4-triazol-3-one monohydrochloride

Chemical Properties

White Solid

Originator

Etoperidone,ZYF Pharm

Uses

A psychotropic drug related structurally to trazodone. Antidepressant.

Manufacturing Process

(a). 3,4-Diethyl-δ2-1,2,4-triazolin-5-one (62 g) is dissolved in anhydrous dioxane (about 500 ml) and NaH (21 g) in a 50 percent oily suspension is added. The solution is heated for 30 min under reflux and NmetachlorophenyI- N'-(3-chloro-n-propyl)piperazine (119 g) is added under stirring. The solution is heated for 20 hours under reflux. The solvent is then eliminated under reduced pressure and the residue is treated with 2 N HCl. The solution is washed with ether so as to eliminate the oil present in the hydride solution, and made alkaline with 50% K2CO3. It is extracted with ether and dried, the solvent is eliminated and the residue is distilled under reduced pressure. 115 g of 2-(3-(4-(3-chlorophenyl)-1-piperazinyl)propyl)- 4,5-diethyl-2,4-dihydro-1,2,4-triazol-3-one are obtained. B.P. 230°C/0.5 mm.
2-(3-(4-(3-Chlorophenyl)-1-piperazinyl)propyl)-4,5-diethyl-2,4-dihydro-1,2,4- triazol-3-one hydrochloride was prepared by standard procedures, melting point 197-198°C (recrystallization from isopropanol).
(b). 3,4-Diethyl-δ2-1,2,4-triazolin-5-one (1 g) and 3-bromo-1-chloropropane (6.6 g) are added to a solution of Na (0.98 g) in methanol (20 ml). The solution is refluxed until the pH becomes neutral, poured into water, extracted with ether. The solvent is eliminated and the residual oil is distilled. 1-(3- Chloropropyl)-3,4-diethyl-δ2-1,2,4-triazolin-5-one boils at 121°C/0.05 mm.
1-(3-Chloropropyl)-3,4-diethyl-δ2-1,2,4-triazolin-5-one (1.0 g), NmetachlorophenyIpiperazine (0.9 g) and triethylamine (0.46 g) in toluene (25 ml) are refluxed for 12 hours. The solution is treated with 5 N NaOH, extracted with ether and steam-distilled. The residue is extracted with ether and the ethereal solution is treated with ethereal HCl. 2-(3-(4-(3- Chlorophenyl)-1-piperazinyl)propyl)-4,5-diethyl-2,4-dihydro-1,2,4-triazol-3- one hydrochloride has melting point 197-198°C (recrystallization from isopropanol).

Therapeutic Function

Antidepressant, Anxiolytic