Analogs of propranolol. Synthesis of 3‐alkylamino‐1‐(3‐benzo[ b ]thienyloxy)‐2‐propanols

The synthesis by two alternative routes of 1‐(3‐benzo[ b ]thienyloxy)‐3‐isopropylamino‐2‐propanol hydrochloride ( 1a HCl), a thiophenic isoster of Propranolol, and related compounds, is reported. The protecting and enolizing properties of the 2‐methoxycarbonyl group on benzo[ b ]thiophene‐3‐one, along with its facile removal, are utilized in the first route. In the second one, conversion of 3‐bromobenzo[ b ]thiophene in 1‐(3‐benzo[ b ]thienyloxy)‐2,3‐ o ‐isopropylidenepropane is the key step. On the other hand, hydrolysis of 1‐(3‐benzo[ b ]furanyloxy)‐2,3‐ o ‐isopropylidenepropane to the corresponding diol, in order to obtain a furanic isoster of Propranolol (17a ), was unsuccessful.