1,3,4,5-Tetrahydrobenz[cd]indoles and related compounds. Part III

Abstract

Syntheses of derivatives of the isomeric 4-amino-? ,3,4,5-tetrahydrobenz[cd]indol-5-ols (1) and (6) and the structurally similar 4-amino-2a,3,4,5-tetrahydroacenaphthen-5-ols ( 2 2 ) and (28), and of certain N-alkyl and NN-dimethyl derivatives are described. Preparation of the tetrahydrobenz[cd] indole series was made possible by the use of the tosyl group for protection of the indole imino-group.

N-Arylsulfonylindole Derivatives as Serotonin 5-HT6Receptor Ligands

“…The fact that substitution of the phenyl ring by either electronwithdrawing or electron-donating groups did not improve affinity over the unsubstituted compound (19) was also found by Glennon and co-workers. 16 Replacement of the phenyl ring by the bulkier 2-naphthyl group (25) or by a 2-thiophene (26) gave compounds with only slightly reduced affinity, and the sulfonyl moiety could be replaced by a carbonyl group as in 27 with 11-fold loss in affinity.…”

“…4-Amino-1-(4-methyl)benzenesulfonyl-1,3,4,5-tetrahydrobenz[ cd ]indol-5-ol (17) . To a solution of sodium borohydride (1 g) in absolute ethanol (75 mL) was added dropwise via cannula a suspension of (±)-4-amino-3,4-dihydro-1-[(methylphenyl)sulfonyl]benz[ cd ]indol-5(1 H )one hydrochloride ( 16 ) 25 (4.55 g) in absolute ethanol (150 mL) over 15 min, keeping the internal temperature below 3 °C. The resulting mixture was stirred at −2 °C for 1 h 40 min under nitrogen before it was carefully acidified with 2 N aqueous HCl (28 mL).…”

“…trans-4-(Dimethylamino)-1-(4-methylbenzenesulfonyl)-1,3,4,5-tetrahydrobenz[ cd ]indol-5-ol (49) . A solution of 17 (3.97 g, 11.59 mmol) in absolute ethanol (150 mL), aqueous formaldehyde (38% w/v; 9.2 mL) and glacial acetic acid (92 mL) was hydrogenated at 30 psi over 10% palladium on carbon (1.56 g) for 65 h. The catalyst was removed by filtration and washed with absolute ethanol, and the filtrate was evaporated. The residue was dissolved in dichloromethane (40 mL) and washed with 10% aqueous NaHCO 3 (100 mL).…”

“…The tetrahydrobenz[ cd ]indole derivatives were synthesized from (±)-4-amino-3,4-dihydro-1-[(4-methylbenzyl)sulfonyl]-1,3,4,5-tetrahydrobenz[ cd ]indol-5(1 H )-one hydrochloride ( 16 ) by reduction of the ketone with sodium borohydride to give a 9:1 mixture of trans/cis amino alcohols ( 17 ) (Scheme ). The mixture was then dimethylated by reductive alkylation, and the trans isomer ( 49 ) was separated from the cis isomer by column chromatography.…”

Synthesis and Reactivity of Uhle’s Ketone and Its Derivatives

“…As described in Scheme 23, the tricyclic compounds were obtained starting from N-sulfonyl--amino-Uhle's ketone 117. 44 Reduction of -amino ketone 117 with NaBH 4 gave a 9:1 mixture of trans/cis-amino alcohol 118 in almost quantitative yield, highlighting once again the good propensity of the ketone towards reduction as already pointed out by Uhle in the seminal paper showing its reduction with lithium aluminum hydride in ether solution in an excellent yield.…”