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Synthesis of 6,7,8,9‐tetrahydro‐ N,N ‐di‐ n ‐propyl‐1 H ‐benz[g] indol‐7‐amine, a potential dopamine receptor agonist
Author(s) -
Demopoulos Vassilis J.,
Gavalas Antonis,
Rekatas George,
Tani Ekaterini
Publication year - 1995
Publication title -
journal of heterocyclic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.321
H-Index - 59
eISSN - 1943-5193
pISSN - 0022-152X
DOI - 10.1002/jhet.5570320408
Subject(s) - chemistry , agonist , stereochemistry , sulfonamide , acetaldehyde , bioisostere , amine gas treating , medicinal chemistry , pyrrole , indole test , aldol condensation , acetal , chemical synthesis , receptor , organic chemistry , ethanol , catalysis , biochemistry , in vitro
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.