Synthesis of further amino-halogen-substituted phenyl-aminoethanols

Starting from clenbuterol as a lead structure, new 4-amino-phenyl-aminoethanol analogues have been synthesized by different approaches. In these compounds one or both of the chlorine atoms of clenbuterol are replaced by other residues. This has led to compounds with high intrinsic beta 2-mimetic and/or beta 1-blocking activities. 1-(4-Amino-3-chloro-5-trifluoromethyl-phenyl)-2-tert.-butylamino-ethanol hydrochloride (mabuterol) has been selected for clinical development. A detailed description is given also of the syntheses of intermediary new acetophenone derivatives as well as of the resolution of mabuterol into its enantiomers.