2,2-Dimethoxypropane → HCID 66743896, compound

Participants

Reaction Conditions

Reaction Steps

A mixture of 5-bromo-3-[(pyridin-3-ylmethyl)amino]thiophene-2-carboxamide (175 mg, 0.56 mmol), 2,2-dimethoxypropane (1.5 mL), CSA (13 mg, 0.056 mmol), MgSO4 (150 mg) and DMA (1.5 mL) was microwave-irradiated at 120° 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 water and brine, dried over Na2SO4 and filtered. After removal of the solvent at reduced pressure, a brown solid was obtained. A flask was charged with this solid, 1,2-dimethoxyethane (5.0 mL), tert-butyl 3-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylate (518 mg, 1.68 mmol), sodium carbonate (168 mg, 2.80 mmol) and water (2.5 mL). The flask was purged with argon. Then, 1,1′-bis(diphenylphosphino)ferrocenepalladium (II) dichloride dichloromethane adduct (41 mg, 0.056 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 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, 80:20 hexane/EtOAc to EtOAc then to 90:10 EtOAc/MeOH), then crystallized from MeOH/EtOAc) to give the title compound (64 mg, 32%, 3 steps) as a pale yellow solid:

Provenance & Evidence