Synthesis of 4‐methylfuro[3′,2′:5,6]benzofuro[3,2‐c]pyridine

Abstract

4‐Methylfuro[3′,2′:5,6]benzofuro[3,2‐c]pyridine (3) was synthetized from 2‐acetylfuro[3,2‐f]benzo[b]furan (4) or from 2‐acetyl‐5,6‐dihydrofuro[3,2‐f]benzo[b]furan (10). The key step involves a rearrangement‐cyclization of azides 6 and 12 to form 4‐methylfuro[3′,2′:5,6]benzofuro[3,2‐c]pyridin‐1(2H) one (7) and 8,9‐dihydro‐4‐methylfuro[3′,2′:5,6]benzofuro[3,2c]pyridin‐1(2H)‐one (13). Introduction of an aminoalkyl chain on carbon 1 was effected by substitution of 1‐chloro‐4‐methylfuro[3′,2′:5,6]benzofuro[3,2‐c]pyridine (8).

Enantiospecific Synthesis and Pharmacological Evaluation of a Series of Super-Potent, Conformationally Restricted 5-HT2A/2C Receptor Agonists

“…Representative Procedure for Aromatization of Substituted 2,3,6,7-Tetrahydrobenzo[1,2- b ;4,5- b ‘ ]difurans to Benzo[1,2- b ;4,5- b ‘ ]difurans: ( R ) - (+)- N -Trifluoroacetyl-1-(benzo[1,2- b ;4,5- b ‘ ]difuran-4-yl)-2-aminopropane (( R )- 16). A solution of DDQ (0.42 g, 1.85 mmol) in dioxane (8 mL) was slowly added to a solution of protected amine ( R )- 15 (0.20 g, 0.63 mmol) in dioxane (10 mL) . The solution was heated at reflux for 24 h, at which time TLC indicated reaction completion.…”

“…The aromatic counterpart of this "non-parasubstituted" amphetamine analogue was synthesized by oxidation of (R or S)-15 with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) to produce the aromatized amide (R or S)-16. 14 Subsequently, alkaline hydrolysis and acidification was used to obtain the hydrochloride salt of (R or S)-6a.…”

“…A solution of DDQ (0.42 g, 1.85 mmol) in dioxane (8 mL) was slowly added to a solution of protected amine (R)-15 (0.20 g, 0.63 mmol) in dioxane (10 mL). 14 The solution was heated at reflux for 24 h, at which time TLC indicated reaction completion. The reaction was then cooled to room temperature and the precipitate that formed was removed by vacuum filtration.…”

“…The N -protected arylalkylamine ( R or S )- 15 was hydrolyzed in base and then acidified to afford the hydrochloride salt of the unsubstituted product ( R or S )- 5a . The aromatic counterpart of this “non- para -substituted” amphetamine analogue was synthesized by oxidation of ( R or S )- 15 with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) to produce the aromatized amide ( R or S )- 16 . Subsequently, alkaline hydrolysis and acidification was used to obtain the hydrochloride salt of ( R or S )- 6a .…”