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

Article abstract of DOI:10.1002/jhet.5570320408

In this work, the synthesis of 6,7,8,9-tetrahydro-N,N-di-n-propyl-1H-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 typo 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-1H-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-toluenesulfonyl)-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.