Synthesis of 5‐fluoro‐3‐[3‐[4‐(2‐[14C]‐5‐methoxy‐4‐pyrimidinyl)‐1piperazinyljpropypiperazinyl]propyl]‐1H‐indole dihydrochloride

Abstract

AbstractThe synthesis of 5‐Fluoro‐3‐[3‐[4‐(2‐[14C]‐5‐methoxy‐4‐pyrimi‐dinyl)‐1‐piperazinyl]propyl]‐1H‐indole dihydrochloride (5) was achieved by coupling [14C] formamidine acetate (1) and dimethylmethoxymalonate in methanol containing sodium methoxide at 60°C to provide 2‐[14C] 4,6‐dihydroxy‐5‐methoxyprimidine (2). Reaction of (2) with phosphorous oxychloride produced the unstable chloro‐compound (3) which was reacted with 5‐Fluoro‐3‐(3‐N‐piperazinylpropyl) indole to give 5‐Fluoro‐3[3‐[4‐(2‐[14C]‐6‐chloro‐5‐methoxy‐4‐pyrimidinyl)‐1‐piperazinyl] propyl]‐1H‐indole (4). Catalytic reduction of (4) and addition of 2 equivalents of hydrochloric acid resulted in the title compound as the dihydrochloride (5).