5-Chlorosalicylic Acid → HCID 89545449, compound

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).

1. temperatureThe reaction mixture was heated
2. temperatureat reflux for 1 h, at which point a clear solution
3. customwas obtained
4. concentrationwas concentrated in vacuo
5. dissolutionThe residue was dissolved in dichloromethane (10 mL)
6. washwashed with 1 N hydrochloric acid (2×7 mL), water (2×7 mL) and brine (10 mL)
7. dry with materialThe organic phase was dried over anhydrous sodium sulfate
8. concentrationconcentrated in vacuo
9. customThe residue was purified by column chromatography
10. washeluting with a 10-60% gradient of ethyl acetate in hexanes

ORD record

ord-259bf4b06d64492abc0df0f8c4d658d6

Source dataset

uspto-grants-2016_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09365578B2