Combinatorial chemistry. Preparation of phenoxypropanolamines

An efficient solid-phase parallel synthesis of aryloxypropanolamines is des cribed. Mitsunobu coupling was used to attach (R)-(+)- and (S)-(-)-glycidol to resin-bound phenols, then the epoxide ring was opened with amines. A 25 -member array was synthesized on Wang resin with a sarcosine handle. The ov erall yield was about 70%. A 'split and mix' approach was used to prepare a 5800-member bead bound combinatorial library on Pink amide resin. Magic an gle NMR was used to monitor the reaction progress on the resin. Analysis by LC-MS revealed that > 70% of the beads examined contained an identifiable product that was > 70% pure by HPLC. (C) 2000 Elsevier Science Ltd. All rig hts reserved.