5-Chlorosalicylic Acid → HCID 89545449, compound

Participants

Reaction Steps

To a suspension of 5-chlorosalicylic acid (0.96 g, 5.6 mmol) in dichloromethane (13 mL) was added thionyl chloride (2 mL, 28 mmol) and N,N-dimethylformamide (˜3 drops). The reaction mixture was heated at reflux for 1 h, at which point a clear solution was obtained. The mixture was allowed to cool to ambient temperature and was concentrated in vacuo. The residue was dissolved in dichloromethane (10 mL), and pyrazin-2-ylmethanamine (0.80 g, 4.6 mmol), N,N-diisopropylethylamine (1.6 mL, 9.3 mmol), and 4-(N,N-dimethylamino)pyridine (0.056 m, 0.5 mmol) were added. The reaction mixture was stirred at ambient temperature for 16 h, diluted with dichloromethane (70 mL) and washed with 1 N hydrochloric acid (2×7 mL), water (2×7 mL) and brine (10 mL). The organic phase was dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was purified by column chromatography eluting with a 10-60% gradient of ethyl acetate in hexanes to afford 5-chloro-2-hydroxy-N-(pyrazin-2-ylmethyl)benzamide as a yellow solid in 31% yield (0.379 g): 1H NMR (300 MHz, CDCl3) δ12.10 (s, 1H), 8.67 (s, 1H), 8.57 (s, 2H), 7.57 (br s, 1H), 7.46 (d, J=2.1 Hz, 1H), 7.34 (dd, J=8.9, 1.8 Hz, 1H), 6.93 (d, J=8.9 Hz, 1H), 4.78 (d, J=4.8 Hz, 2H); MS (ES+) m/z 264.0 (M+1), 266.0 (M+1).

Provenance & Evidence