Synthesis of isotope‐labeled HSP90 inhibitor: [13CD3] and [14C]‐TAK‐459 |
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Authors: | Mihaela Plesescu Eric L. Elliott Yuexian Li Shimoga R. Prakash |
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Affiliation: | Department of Drug Metabolism and Pharmacokinetics, Isotope Chemistry Group, Millennium Pharmaceuticals Inc, Cambridge, MA, USA |
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Abstract: | [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‐dihydropyrido[4,3‐d]pyrimidin‐5(6H)‐one, was prepared by microwave‐assisted condensation. |
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Keywords: | [13CD3]‐TAK‐459 [14C]‐TAK‐459 microwave chemistry HSP90 inhibitor |
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