Synthesis of 6,7,8,9‐tetrahydro‐<i>N,N</i>‐di‐<i>n</i>‐propyl‐1<i>H</i>‐benz[g] indol‐7‐amine, a potential dopamine receptor agonist

Abstract

Abstract In this work, the synthesis of 6,7,8,9‐tetrahydro‐ N,N ‐di ‐ n ‐propyl‐1 H ‐benz[ g ]indol‐7‐amine (1) is described. This compound was designed as an indole bioisostere to the known dopamine receptor agonist 5‐OH‐aminotetraline 2 . The key step of the synthesis was a Mukaiyama type aldol condensation between the dimethyl acetal of 1‐( p ‐toluenesulfonyl)pyrrole‐3‐acetaldehyde ( 4 ) and 4‐di‐ n ‐propylamino‐1‐trimethylsilyloxycyclohexene ( 8 ) followed by cycloaromatization to afford 1‐ p ‐toluenesulfonyl‐6,7,8,9‐tetrahydro‐ N,N ‐di‐ n ‐ propyl‐1 H ‐benz[ g ]indol‐7‐amine ( 10 ). Scission of the sulfonamide bond in 10 gave the target compound 1 . A byproduct which was isolated was assigned to the structure of 1‐( p ‐toluenesul‐fonyl)‐6‐[3‐[1‐( p ‐toluenesulfonyl)]pyrrolyl]indole ( 11 ). This compound was also synthesized in good yield by an acid catalyzed dimerization of the dimethyl acetal of 1‐( p ‐toluenesulfonyl)pyrrole‐3‐acetaldehyde ( 4 ). Preliminary screening of 1 indicated that it possesses central dopamine receptor agonist properties.