2,2-Dimethoxypropane → Cdc7-IN-15

Participants

Reaction Conditions

Reaction Steps

A mixture of 3-amino-5-bromothiophene-2-carboxamide (1.99 g, 9.0 mmol), 2,2-dimethoxypropane (10 mL), CSA (209 mg, 0.90 mmol), MgSO4 (2.17 g, 18 mmol) and DMA (10 mL) was stirred at 90° C. for 2 h. After removal of MgSO4 by filtration, saturated aqueous NaHCO3 was added to the filtrate. 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 brown crystalline solid was obtained. A flask was charged with this solid, tert-butyl 3-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylate (6.0 g, 19.5 mmol), sodium carbonate (2.3 g, 38.3 mmol), 1,2-dimethoxyethane (30 mL) and water (15 mL). The flask was purged with argon. Then, 1,1′-bis(diphenylphosphino)ferrocenepalladium (II) dichloride dichloromethane adduct (626 mg, 0.766 mmol) was added to the mixture. The flask was purged with argon again. After stirring at 100° C. for 3.5 h, 8 M aqueous NaOH (2.0 mL) was added. After stirring at 100° C. for 1 h, the organic materials were extracted with EtOAc/THF. The combined extracts were dried over Na2SO4 and filtered. After removal of the solvent at reduced pressure, the residue was purified by column chromatography (Purif, silica gel, EtOAc to 90:10 EtOAc/MeOH) to give the title compound (1.97 g, 86%) as a brown solid:

Provenance & Evidence