p-Toluenesulfonic acid → HCID 66743650, compound

Participants

Reaction Steps

A mixture of 5-bromo-3-(methylamino)thiophene-2-carboxamide (235 mg, 1.00 mmol), 1,1,1-trifluoroacetone (2.00 mL, 22.3 mmol), PTSA (19.0 mg, 0.100 mmol), MgSO4 (120 mg, 1.00 mmol) and DMF (2 mL) was microwave-irradiated at 130° C. for 2 h then at 140° C. for 4 h. Then, the mixture was poured into saturated aqueous NaHCO3 (100 mL). Extraction with EtOAc (100 mL×2), washing with brine, drying over MgSO4, filtration and concentration under reduced pressure gave a dark solid. This residue was mixed with sodium carbonate (530 mg, 5.00 mmol), 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (582 mg, 3.00 mmol), 1,2-dimethoxyethane (2.5 mL) and water (5 mL). The mixture was purged with argon. Then, 1,1′-bis (diphenylphosphino)ferrocenepalladium (II) dichloride dichloromethane adduct (82 mg, 0.10 mmol) was added, and the mixture was purged with argon again. This mixture was refluxed overnight. Then, the mixture was poured into saturated aqueous NaHCO3 and extracted with EtOAc, and the extract was dried over MgSO4, filtered and concentrated at reduced pressure to give a dark oil. This residue was purified by column chromatography (Purif, silica gel, hexane to EtOAc) to give a dark solid (29 mg). This solid was triturated with EtOAc/hexane and collected by filtration to afford the title compound (13.6 mg, 4.3%) as a beige solid:

Provenance & Evidence