Triethylamine → 4-(2-Bromo-5-fluorophenoxy)-1-[5-(1H-pyrrol-3-yl)-1,2,4-oxadiazol-3-yl]piperidine

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Reaction Steps

To a mixture of pyrrole-3-carboxylic acid hydrate (93 mg, 0.723 mmol) in THF (2007 μL) was added oxalyl chloride (264 μL, 3.01 mmol) followed by DMF (10 μL) at 0° C. The mixture was warmed to rt and stirred for 0.5 h. The solvent was evaporated, the residue diluted with THF (1 mL), evaporated again and dried under high vacuum. The residue was diluted with THF (2007 μL), 4-(2-bromo-5-fluorophenoxy)-N′-hydroxypiperidine-1-carboximidamide (200 mg, 0.602 mmol) was added followed by triethylamine (252 μL, 1.806 mmol). The mixture was stirred at rt for 0.5 h, then heated at 80° C. for 1 h. The mixture was cooled to RT and then sodium hydride (72.2 mg, 1.806 mmol) was added. The mixture was stirred at RT for 0.5 h and then heated at 80° C. for 1 h. The solvent was evaporated and the residue diluted with water (2 mL). The aqueous layer was extracted with EtOAc (3×2 mL). The combined organic fractions were dried over Na2SO4 and the solvent was evaporated. Purification by Combiflash chromatography (SiO2-12 g, gradient elution of 30-60% EtOAc/hexanes over 25 min) afforded the title product. 1H NMR (500 MHz, acetone-d6): δ7.61 (s, 2H), 7.11 (s, 1H), 6.99 (s, 1H), 6.75 (s, 1H), 6.65 (s, 1H), 4.89 (s, 1H), 3.76 (s, 2H), 3.54 (s, 2H), 1.99-1.82 (m, 2H), 2.10 (s, 2H). MS: m/z 407, 409 (MH+).

Provenance & Evidence