Amino Diol Based Asymmetric Syntheses of a Fused Benzazepine as a Selective D1 Dopamine Receptor

Abstract

A six-step practical synthesis of (6aS,13bR)-11-chloro-6,6a,7,8,9,13b-hexahydro-7-methyl-5H-benzo[d]naphtho[2,1-b]azepin-12-ol, a selective D1 dopamine receptor, is developed starting from (1S,2S)-phenyl-2-amino-1,3-propanediol. An acid-promoted stereo- and regioselective cyclization of the benzazepine ring was established. Three double reactions in which two functional groups are transformed in a single step were developed. These include the double hydrolysis, the double reduction, and the cyclization and demethylation. The use of practical and economical reagents reduced the cost significantly.