Dimethylformamide → 2-(pyridin-3-yl)-N-{3-[4-(trifluoromethoxy)phenyl]pyrazolo[1,5-a]pyrimidin-2-yl}acetamide

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Reaction Steps

3-Pyridylacetic acid hydrochloride (41.6 mg, 0.239 mmol) was suspended in dichloromethane (3.0 mL). Oxalyl chloride (24 μL, 0.28 mmol) and a drop of dimethylformamide were added and the mixture was stirred at ambient temperature for 90 minutes. The reaction mixture was concentrated under vacuum. To this residue was added a solution of the product from Example 1C (59 mg, 0.2 mmol) in pyridine (2.0 mL). The mixture was stirred at ambient temperature for 1 hour and then at 40° C. for 1 hour. The reaction mixture was concentrated under vacuum and purified by reverse-phase HPLC [Waters XBridge™ RP18 column, 5 μm, 30×100 mm, flow rate 40 mL/minute, 30-100% gradient of methanol in buffer (0.1 M aqueous ammonium bicarbonate, adjusted to pH 10 with ammonium hydroxide)] to afford 24 mg (29%) of the title compound. 1H NMR (400 MHz, CD3OD) δ ppm 8.86 (d, J=5.8 Hz, 1H), 8.52-8.59 (m, 2H), 8.44-8.49 (m, 1H), 7.79-7.89 (m, 1H), 7.71-7.74 (m, 2H), 7.33-7.44 (m, 1H), 7.20-7.23 (m, 2H), 7.07 (dd, J=7.0, 4.1 Hz, 1H), 3.81 (s, 2H); MS (ESI) m/z 414 (M+H)+.

Provenance & Evidence