HCID 57474480, compound → HCID 178511926, compound

Participants

Reaction Steps

1-(4-(1H-imidazol-1-yl)butyl)-6-nitro-1H-indole (compound 166, 145 mg, 0.510 mmol) was dissolved in anhydrous ethanol (7 mL) in a dry argon purged flask. Palladium, 10 wt % on activated carbon (54.2 mg, 0.051 mmol) is quickly added and the atmosphere from the flask evacuated by vacuum pump and replaced with hydrogen from a balloon. The atmosphere is evacuated from the flask and replaced with hydrogen twice more and the mixture stirred under a hydrogen atmosphere at room temperature. After 3 hours, thin layer chromatography in a solvent system of (10% 2M NH3 in methanol/90% dichloromethane) shows complete conversion to compound 167, 1-(4-(1H-imidazol-1-yl)butyl)-1H-indol-6-amine, which is utilized without isolation. The mixture is filtered through a pad of celite to remove insolubles, the pad washed with anhydrous ethanol (7 mL) and the ethanolic solution of the amine 167 is charged to a small, argon purged flask fitted with a magnetic stir bar. Thiophene-2-carboximidothioic acid methyl ester hydroiodide (189.1 mg, 0.663 mmol) is added to the flask and the reaction was stirred under Ar at ambient temperature for 20 hours, at which time the solution was diluted with diethyl ether (100 ml) resulting in the formation of a sticky solid which could not be isolated via filtration. As a result the product was washed off the funnel with methanol, combined with the filtrate and solvents evaporated to leave a crude residue. The residue was partitioned between H2O and ethyl acetate and 3M sodium hydroxide solution added to adjust pH to 9. The mixture was transferred to a separatory funnel and the organic layer collected. The aqueous layer was further extracted with ethyl acetate and the combined organic layers were washed with brine, dried over magnesium sulfate, filtered, concentrated and the residue purified via chromatography on silica gel (2.5% 2M NH3 in methanol/97.5% dichloromethane) to yield yellow solid, compound 168 (101 mg, 54.5% yield); 1H-NMR (DMSO-d6) δ 7.74 (d, 1H, J=3.0), 7.60 (d, 1H, J=5.2), 7.56 (s, 1H), 7.45 (d, 1H, J=8.3), 7.21 (d, 1H, J=3.0), 7.13-7.06 (m, 2H), 6.92 (s, 1H), 6.85 (s, 1H), 6.59 (d, 1H, J=8.0), 6.42-6.30 (br, 2×m, 3H), 4.17-4.06 (m, 2H), 3.99-3.92 (m, 2H), 1.75-1.58 (m, 4H); MS (ESI+): 364 (M+1, 100%).

Provenance & Evidence