Synthesis of [4,6-3H]-2-pyridone and [3H]-RS-91309

Article abstract of DOI:10.1002/jlcr.2580360808

We describe herein, a novel synthesis of the previously unreported compound, 4,6-dibromo-2-pyridone (3) and its use in the preparation of [³H]-RS-91309, a potassium channel modulator. This key intermediate, (3), was reduced with carrier free tritium gas to furnish [4,6-³H]-2-pyridone (9) having a specific activity of 50 Ci/mmole. Condensation of (9) with epoxide (10), followed by elaboration of the resulting chromene methyl group of (12) gave [³H]-RS-91309 (14) whose specific activity was also 50 Ci/mmole. This chemistry, as well as the solution of several microscale related stoichiometry problems is discussed.