| Abstract
| - SR 121463 A, 1, is a promising nonpeptide prototype for potent and selective antagonism of thevasopressin V2 receptor subtype and, thus, a candidate for control of the clinically debilitatingcondition of hyponatremia and its associated syndromes. In the present work, we present a noveland stereoselective synthesis that stems from the preparation of three key intermediates: thesubstituted benzenesulfonyl chloride 2, the N-protected oxindole 3, and protected dibromide 4. Thesynthesis of 1 has been achieved in good overall yield, each step proceeding in greater than 80%yield. In addition, intermediate 2 and the syn isomer of 1 were prepared with complete control ofstereochemistry. The latter reduction appears to proceed by lithium cation mediated chelationcontrol. Molecular mechanics calculations with the MM3* and MMFF force fields underscoregeometric and energetic aspects of the reaction.
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