An improved synthesis of enantiomerically pure RWJ 69442, a development candidate for the treatment of benign prostatic hyperplasia

This report describes an improved synthesis of enantiomerically pure (S)-2- [4-(Dimethylamino)phenyl]-2,3-dihydro-N-[2-hydroxy-3-[4-[2-(1-methylethoxy) -phenyl]-1-piperazinyl]propyl]-1,3-dioxo-1H-isoindole-5-carboxamide (RWJ 69 442), a potent and selective alpha (1a)-adrenergic receptor antagonist for the treatment of benign prostatic hyperplasia. The synthesis highlights les s hazardous reagents, easier purification and higher enantiomeric purity. T he N-benzyl-N-t-butoxycarbonyl amine 6 could serve as an enantiomerically p ure chiral building block for asymmetric synthesis.