p-Toluenesulfonic acid → HCID 66743248, compound

Participants

Reaction Conditions

Reaction Steps

A mixture of 5-bromo-3-[(2-hydroxyethyl)amino]thiophene-2-carboxamide (100 mg, 0.377 mmol), acetone (1.0 mL), PTSA (6.5 mg, 0.038 mmol) and acetic acid (1.0 mL) was stirred at 70° C. for 1 h. The mixture was poured into saturated aqueous NaHCO3. The organic materials were extracted with EtOAc. The combined extracts were washed with brine, dried over Na2SO4 and filtered. After removal of the solvent at reduced pressure, a pale brown amorphous solid was obtained. A flask was charged with the amorphous, 1,2-dimethoxyethane (3.0 mL), tert-butyl 3-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylate (349 mg, 1.13 mmol), sodium carbonate (113 mg, 1.89 mmol) and water (1.5 mL). The flask was purged with argon. Then, 1,1′-bis(diphenylphosphino)ferrocenepalladium (II) dichloride dichloromethane adduct (31 mg, 0.038 mmol) was added to the mixture. The flask was purged with argon. After stirring at 100° C. for 1 h, 8 M aqueous NaOH (1.0 mL) was added. After stirring at 100° C. for 1.5 h, the organic materials were extracted with EtOAc/THF. The combined extracts were washed with brine, dried over Na2SO4 and filtered. After removal of the solvent at reduced pressure, the residue was purified by column chromatography (Purif, silica gel, 90:10 hexane/EtOAc to EtOAc then to 90:10 EtOAc/MeOH), then crystallized from MeOH/EtOAc/hexane) to give the title compound (40 mg, 35%) as a pale brown solid:

Provenance & Evidence