Originator
Proketazine,Wyeth,US,1962
Manufacturing Process
As described in US Patent 3,023,146, in a round-bottomed flask were placed
35 g of 2-propionyl phenothiazine (0.14 mol) 7 g of 50% sodium hydride in
mineral oil (0.14 mol), and 240 cc of dimethyl formamide dried over sodium
hydride. The resultant solution was stirred at room temperature for 2 hours,
and then 88 g (0.56 mol) of trimethylene chlorobromide was added at once.
The mixture was stirred for 2 hours, heated at 60 to 70°C for 1 hour and
poured into 2 liters of H2O. The resulting suspension was extracted with ether,
the ether layer separated and the ether removed under vacuum. A gummy
mass remained which was dissolved in decalin and the solution was partly
distilled to remove excess chlorobromide. After removal of most of the decalin
under vacuum, the residue was treated with a large excess of N-(β-
hydroxyethyl)-piperazine and heated on a steam bath for 2 hours. This
material was extracted with dilute aqueous HCl, this acid layer neutralized
with aqueous base and the resulting oil extracted into ether. The ether layer
was washed with water until the washings were neutral and dried over
anhydrous potassium carbonate. On treatment with maleic acid in ether a
yellow solid separated which was recrystallized from isopropanol. This yellow
solid had MP 175° to 177°C.
