Synthesis of isotope‐labeled HSP90 inhibitor: [13CD3] and [14C]‐TAK‐459

¹³CD₃]‐TAK‐459 (1A), an HSP90 inhibitor, was synthesized from ¹³CD₃]‐sodium methoxide in three steps in an overall yield of 29%. The key intermediate ¹³CD₃]‐2‐methoxy‐6‐(4,4,5,5‐tetramethyl‐1,3,2‐dioxaborolan‐2‐yl)pyridine was synthesized in two steps from 2,6‐dibromopyridine and stable isotope‐labeled sodium methoxide. ¹⁴C]‐TAK‐459 (1B) was synthesized from ¹⁴C(U)]‐guanidine hydrochloride in five steps in an overall radiochemical yield of 5.4%. The key intermediate, ¹⁴C]‐(R)‐2‐amino‐7‐(2‐bromo‐4‐fluorophenyl)‐4‐methyl‐7,8‐dihydropyrido4,3‐d]pyrimidin‐5(6H)‐one, was prepared by microwave‐assisted condensation.