Ammonia → HCID 178511871, compound

Participants

Reaction Steps

Compound 17 (250 mg, 0.686 mmol) and anhydrous ethanol (15 mL) were charged to a dry argon purged flask fitted with magnetic stirbar. Thiophene-2-carboximidothioic acid methyl ester hydroiodide (254.3 mg, 0.891 mmol) is added to the flask and the reaction was stirred under argon at ambient temperature for 48 hours at which time, thin layer chromatography in a solvent system of 2M NH3 in methanol:CH2Cl2, 5:95 (developed twice) shows incomplete consumption of 17. A condenser was added and the mixture heated to reflux for 5 hours. An additional amount of the thiophene-2-carboximidothioic acid methyl ester hydroiodide (0.2 eq) was added and stirring continued at 65° C. for an additional 24 hours. A further portion of thiophene-2-carboximidothioic acid methyl ester hydroiodide (0.2 eq) was added and stirring continued for an additional 18 hours at reflux. After cooling to room temperature, the solution was diluted with diethyl ether (150 ml) resulting in the formation of off-white precipitate that was collected on a sintered glass funnel and washed with ether. The solid was partitioned between H2O and ethyl acetate and 3M sodium hydroxide solution added to adjust pH to 9-10. 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 residue purified via chromatography on silica gel (2M NH3 in methanol:CH2Cl2, 2.5:97.5) to afford orange-yellow solid 18 (69 mg, 21.2%); 1H NMR (DMSO-d6) δ 8.35 (d, 2H, J=8.7 Hz), 7.93 (d, 2H, J=8.7 Hz), 7.73 (d, 1H, J=3.7 Hz), 7.60 (d, 1H, J=5.3 Hz), 7.51 (d, 1H, J=8.6 Hz), 7.10 (m, 1H), 7.07 (s, 1H), 6.80 (d, 1H, J=8.5 Hz), 6.66 (s, 1H), 6.32 (brs, 2H), 4.32 (t, 2H, J=6.5 Hz), 2.49 (m, 2H), 2.21 (m, 4H), 1.31 (m, 6H); ESI-MS (m/z, %): 474 (M+1, 100%).

Provenance & Evidence