SYNTHESIS OF [4,6-H-3]-2-PYRIDONE AND [H-3] RS-91309

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