Tevahdron: Asyrnmerry Vol. 3. No. 4. p,,.539-554.1992 o9574166/92s5.co+.oo Printed in Grcu Briuin PcrguMnPrasLtd S-[l-(2,3-Diaminophenoxy)]-3’-(N-t-butylamino)propan-2t-ol - Simplified Asymmetric Synthesis with CD and Chiral HPLC Analysis Franklin Aigbirhio, Victor W. Pike*, Eric Francottel, Stephen L. Waters,Beaulah Banfleld2, Knut A. Jaeggil and Alex Drake2 MRc ~clo@on unit. Hammersmith Hospital, Dwanc Roa& LQldon W12 OHS, U.K. Qlmmacatical Rwaxh, Ciba Geigy AO. 4002 Basel. Switzabmd. ~artment of Chemistry, Birkbeck College, Gordon Street, Loodon. WCIH OAI. U.K. zyxwvutsrqponmlkjihgfedcbaZ (Received 5 Febr uar y 1992) Key w or ds: S-[I-f ZJ-diamh@ noxy)]-3’-(N-t -b~ uy~ )pr ~ 2’-d; asymmet r ic synt hesir ; chir ol HPLC; CD: S-[car bmyl- W]CGP 12177 A bsfrsc/: S-[ 1~2.3-Dieminophcnoxy)]-3’-(N-1-butyl~~o)~~-~~l is important as a pnxursor in the radiosynthesis of a t zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA ~ C-lab&xl ntdioligaod (S-lcurfwnyl-ttC1CGP 12177) for the study of preceptors io living mao. The asymmeti synthesis of this pnxursor has been simplified based oo the textion of readily available 2-mniu~3- nitropheaol and the chiral auxiliary, S-glycidyl-3-niuob Ipbcmate, followed by treatment of the resulmt S- epoxide with I-butylamine and reduction with hydrogen in the pnxetwe of palladium on carbon. Chiral HPLC methods have been successfully developed to monitor the emmtiomcric purity of the chill auxiliary and of all intermediates itt the. asymmetric synthesis. All intenncdiatcs and products have teeo stodicd by CD. It has been dcmc+utrated by chiral HPLC that S-CGP 12177 can be prepared in > 98.4% e.e. from the synthesised S-precursor. R- CGP 12177 (e.e. > 96.2%) was pqmrcd analogously. INTRODUCTION R,S-CGP 12177 (I) is a potent hydrophilic antagonist at jkulreoergic nxeptors. It has low non-specific binding to membranes and low cellular uptakel.2 and so only binds to cell-surface receptors rather than to internal&d receptors.1 The labelling of R,S-CGP 12177 (I) with the cyclotron-produced positron-emitting radionuclide, carbon-l 1 (Q/Z = 20.4 min),s was soon found to provide a promising radioligand for studying cell- surface B-adtenergic receptors in human heart in vivo by the quantitative and atraumatic technique of positron 539