COMBINATORIAL APPROACHES TO PHARMACOPHORIC HETEROCYCLES - A SOLID-PHASE SYNTHESIS OF 3,1-BENZOXAZINE-4-ONES

An efficient solid-phase synthesis of 3,1-benzoxazine-4-ones is descri bed. Immobilized amino acid based functionalized urea derivatives 2 un dergo a high yielding heterocyclization under mild conditions in prese nce of coupling reagents (DIC, TsCl/Py, or Ac2O) to afford 3,1-benzoxa zine-4-ones 6. The method offers broad scope for structural and chemic al diversity, and is amenable for combinatorial synthesis of 3,1-benzo xazine-4-ones libraries with potential for discovery of novel serine p rotease inhibitors. (C) 1998 John Wiley & Sons, Inc.