Hydrochloride Pioglitazone Ketone Synthesis Method

Pioglitazone hydrochloride, a new type insulin sensitive reagent, belongs to thiazolidine-2, 4-dione compound. It is chiefly selected drug for treating 2 type diabetes. At present how to synthesis is one hot point of drug research for treating diabetes.After analyzing the existed synthesis route, we get a new reasonable synthesis route, then optimize the route and the reaction condition. The details of this route as follows:With the piperidine as catalyst, p-hydroxylbenzaldehyde condensed with thiazolidine-2,4-dione to give 5-(4-hydroxylbenzylidene) thiazolidine -2, 4-dione, which was reduced by hydrogen/Pd-C to afford 5-(4-hydroxybenzyl) thiazolidine- 2,4-dione.The dione subsequently reacted with potassium hydroxide and 2-(5-ethyl-2-pyridyl)ethyl sulfonate to produce pioglitazone, and finally with hydrochloride acid to obtain the hydrochloride salt.We separate or synthesis five impurity, 5-ethyl-2-vinyl-pyridine, 5-ethyl-2-hydroxylethyl -pyridine , 5-[(4-hydroxylbeny l)methyl]-thiazolidine- 2,4-dione, 5-[4-[2- ( 5-ethyl-2-pyridyl ) ethyloxyl] benzylidene]- thiazolidine- 2, 4-dione , 4-[2- ( 5-ethyl-2-pyridyl- ) ethyloxyl]phenyl maethanol, and discuss the condition to control these impurity.