HCID 59004612, compound → HCID 178480160, compound

Participants

Reaction Steps

Compound 12 (95 mg, 0.212 mmol) was dissolved in anhydrous ethanol (10 mL) in a dry argon purged flask. Palladium, 10 wt % on activated carbon (22.6 mg, 0.0212 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 2M NH3 in MeOH:CH2Cl2, 5:95 shows complete conversion to 13, which is utilized without isolation. The mixture is filtered through a pad of celite to remove insolubles, the pad washed with anhydrous ethanol (5 mL) and the ethanolic solution of the amine 13 is charged to a small, argon purged flask fitted with a magnetic stirbar. Thiophene-2-carboximidothioic acid methyl ester hydroiodide (78.6 mg, 0.276 mmol) is added to the flask and the reaction was stirred under argon at ambient temperature for 44 hours. The solution was diluted with diethyl ether (100 ml) and cooled in an ice bath. No precipitate formed thus the solvent was evaporated. The residue was partitioned between H2O and ethyl acetate and 1M 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 sulphate, filtered, concentrated and the crude freebase purified via chromatography on silica gel (2M NH3 in MeOH:CH2Cl2, 2.5:97.5 to 5:95) to yield compound 14 (60 mg, 53.7%) as a yellow solid. 1H NMR (DMSO-d6) δ 1.36-48 (m, 2H), 1.53-1.60 (m, 3H), 1.80-1.86 (m, 1H), 1.92-2.05 (m, 2H), 2.08 (s, 3H), 2.87-2.93 (m, 1H), 4.00 (t, 2H, J=8.0 Hz), 4.19 (s, 2H), 6.12 (s, 1H), 6.23 (brs, 2H), 6.63-6.67 (m, 1H), 6.93 (s, 1H), 7.07-7.10 (m, 1H), 7.26 (d, 1H, J=8.6 Hz), 7.31-7.41 (m, 4H), 7.5 8 (d, 1H, J=5.3 Hz), 7.71 (d, 1H, J=3.7 Hz); ESI-MS (m/z, %): 527 (MH+, 100%).

Provenance & Evidence