Ammonia → HCID 178480155, compound

Participants

Reaction Steps

Compound 20 (97 mg, 0.266 mmol) and anhydrous ethanol (10 mL) were charged to a dry argon purged flask fitted with magnetic stirbar. Thiophene-2-carboximidothioic acid methyl ester hydroiodide (98.7 mg, 0.346 mmol) is added to the flask and the reaction was stirred under argon at ambient temperature for 46 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 20. 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) and ethanol (10 mL) were added and stirring continued for an additional 72 hours at reflux. Thin layer chromatography in a solvent system of 2M NH3 in methanol:CH2Cl2, 5:95 (developed twice) shows incomplete consumption of 20. A further portion of thiophene-2-carboximidothioic acid methyl ester hydroiodide (1.0 eq) was added and the mixture heated to reflux for 6 hours then stirred at ambient temperature for 48 hours. The mixture was filtered through a sintered glass funnel to remove insolubles, the filtrate concentrated and the residue purified using dry silica gel column chromatography eluting with 30 mL portions of solvent system (2M NH3 in methanol:CH2Cl2, 5:95) to afford an orange oil 21 (35 mg, 27.8%); 1H NMR (DMSO-d6) δ 8.36 (d, 2H, J=8.6 Hz), 8.18 (s, 1H), 7.86 (d, 2H, J=8.8 Hz), 7.75 (d, 1H, J=3.2 Hz), 7.61 (d, 1H, J=5.3 Hz), 7.52 (d, 1H, J=8.8 Hz), 7.14-7.05 (2×m, 2H), 6.85-6.80 (m, 1H), 6.69 (s, 1H), 4.29 (m, 2H), 2.91-2.84 (m, 1H), 2.08 and 2.06 (2×s, 3H), 2.03-1.93 (m, 1H), 1.90-1.78 (m, 1H), 1.72-1.63 (m, 1H), 1.61-1.43 (m, 3H), 1.37-1.20 (m, 2H); ESI-MS (m/z, %): 474 (M+1, 100%).

Provenance & Evidence