bis[N,N,N',N'-tetramethyl-3-(10H-phenothiazin-10-yl)propane-1,3-diamine] fumarate

Originator

Jenotone,Coopers

Uses

elephant care

Manufacturing Process

Phenothiazine (20 g) is heated under reflux for 1 hour with sodium amide (5 g) in xylene (80 ml). A solution of 1,3-bis(dimethylamino)-2-chloropropane (27 g) (prepared by a method analogous to that described in Ingold and Rothstein J.C.S. 1931, 1676) in xylene (30 ml) is then added over 2 hours. Heating is continued for a further 1 hour and then the mixture is taken up in water (270 ml) and hydrochloric acid (d=1.19; 20 ml). The decanted acid layer is treated with caustic soda (d 1.33; 25 ml) and the base is extracted with ether (2 x 50 ml) which is then dried over potassium carbonate. On distillation there is obtained at 218-220°C/0.6 mm Hg a mixture (20 g) containing a major proportion of 10-[2,3-bis(dimethylamino)-1- propyl]phenothiazine and a minor proportion of 10-[1,3-bis(dimethylamino)-1- propyl]phenothiazine.
A mixture of bases (11 g) obtained is dissolved in isopropanol (25 ml). Ether (25 ml) containing dry hydrogen chloride (2 g) is added, the mixture is left to crystallise overnight in a refrigerator and the product is filtered off, washed and dried. There is thus obtained a salt (2.5 g), M.P. 244°C, which is 10-[1,3- bis(dimethylamino)-1-propyl]phenothiazine hydrochloride.
On evaporation of the mother liquors from the above hydrochloride a residue is obtained from which is isolated its isomer, 10-[2,3-bis(dimethylamino)-1- propyl]phenothiazine, the base crystallising from ethanol and melting at 58°C. The structure of these two isomers has been confirmed by comparison of their infra-red adsorption spectra with those of related products of known structure.
In practice it is usually used as fumarate.

Therapeutic Function

Spasmolytic