2,2-Dimethoxypropane → HCID 86662299, compound

Participants

Reaction Conditions

Reaction Steps

A mixture of 5-bromo-3-[(2,2-difluoroethyl)amino]thiophene-2-carboxamide (130 mg, 0.456 mmol), 2,2-dimethoxypropane (1 mL), CSA (11 mg, 0.046 mmol), MgSO4 (110 mg, 0.912 mmol) and DMA (1 mL) was stirred at 90° C. for 2 h. Then, saturated aqueous NaHCO3 and EtOAc were added to quench the reaction. The organic materials were extracted with EtOAc. The combined extracts were washed with water and brine, dried over Na2SO4 and filtered. After removal of the solvent at reduced pressure, a colorless crystalline solid was obtained. A flask was charged with the solid, 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 (422 mg, 1.37 mmol), sodium carbonate (137 mg, 2.28 mmol) and water (1.5 mL). The flask was purged with argon. Then, 1,1′-bis (diphenylphosphino)ferrocenepalladium (II) dichloride dichloromethane adduct (37 mg, 0.046 mmol) was added to the mixture. The flask was purged with argon. After stirring at 100° C. for 2 h, 8 M aqueous NaOH (0.5 mL) was added. After stirring at 100° C. for 1 h, 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, the residue was purified by column chromatography (Purif, silica gel, 80:20 hexane/EtOAc to EtOAc), then crystallized from EtOAc/hexane to give the title compound (78 mg, 52%) as a yellow solid:

Provenance & Evidence