Sodium Bicarbonate → HCID 58293764, compound

Participants

Reaction Conditions

Reaction Steps

A round-bottom flask was charged with 5-bromo-3-(1-(2,3-difluoro-4-methylphenyl)-1H-tetrazol-5-yl)pyridin-2-amine (Compound 1073, 3.672 g, 10 mmol), tert-butyl 4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate (Compound 1098, 4.150 g, 11.00 mmol) and DME (100 mL) was bubbled with nitrogen gas for 20 min. A 1.2 M aqueous solution of sodium bicarbonate (25.00 mL, 30.00 mmol) was added and nitrogen flow was continued for another 40 min before addition of PdCl2(dppf)2 (731.7 mg, 1.000 mmol). The suspension was heated at 70° C. for 15 hours, filtered though a layer of diatomaceous earth, and the filtrate washed with brine. The volatiles were removed by vacuum evaporation to afford a residue that was purified by silica gel chromatography, eluting with 20-100% EtOAc/hexanes, to produce tert-butyl 4-(4-(6-amino-5-(1-(2,3-difluoro-4-methylphenyl)-1H-tetrazol-5-yl)pyridin-3-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate as a yellow solid (Compound 1102, 4.0 g, 74%).

Provenance & Evidence