Triethylamine hydrochloride → 5-Fluoro-2-(4-fluorophenoxy)-N-[4-(2H-tetrazol-5-yl)benzyl]nicotinamide

Participants

Reaction Conditions

Reaction Steps

To a solution of N-(4-cyanobenzyl)-5-fluoro-2-(4-fluorophenoxy)nicotinamide (step 1, 220 mg, 0.60 mmol) in 1-methyl-pyrrolidin-2-one (5 mL) were added sodium azide (117 mg, 1.8 mmol) and triethylamine hydrochloride (248 mg, 1.8 mmol) at room temperature. This mixture was heated at 150° C. for 18 h. The reaction mixture was diluted with dichloromethane (100 mL), and the solution was washed with saturated sodium dihydrogenphosphate solution (50 mL). The organic phase was dried (sodium sulfate) and concentrated. The residue was purified by flash column chromatography on silica gel (50 g) eluting with dichloromethane/methanol/acetic acid (100/5/0.5) to give off white solids. The solids were triturated with ethyl acetate to afford 125 mg (50%) of the title compound as white solids: 1H-NMR (DMSO-d6) δ 9.18 (1H, t, J=5.8 Hz), 8.14 (1H, d, J=2.8 Hz), 7.99 (1H, dd, J=8.2, 2.8 Hz), 7.90 (2H, d, J=8.2 Hz), 7.51 (2H, d, J=8.2 Hz), 7.22–7.15 (4H, m), 4.56 (2H, d, J=5.8 Hz); MS (ESI) m/z 409 (M+H)+, 407 (M−H)−.

Provenance & Evidence