Pyridine → 4-Chloro-2-(2-chloro-6-fluorophenyl)-thiazolo[5,4-c]pyridine

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Reaction Steps

A mixture of 2-chloro-N-(2-chloro-3-fluoro-pyridin-4-yl)-6-fluorobenzimidoyl chloride (80 mg, 0.25 mmol), thiourea (76 mg, 1.0 mmol) and pyridine (82 μL, 1.0 mmol) in anhydrous isopropanol (1.5 mL) was heated under reflux, under nitrogen, for 3.5 hours. The reaction mixture was allowed to cool to ambient temperature and then triethylamine (1 mL) was added. The resultant mixture was heated under reflux for a further 1 hour then cooled to ambient temperature. The mixture was concentrated to dryness under reduced pressure and the residue was triturated with DCM, filtered and left to air dry. The crude product was purified by silica gel flash chromatography (0-10% EtOAc in cyclohexane) to give the desired compound as a white solid (65 mg, 86% yield). 1H NMR (400 MHz, CDCl3): δ 8.52 (d, J=5.6 Hz, 1H), 7.99 (d, J=5.6 Hz, 1H), 7.50 (td, J=8.3, 5.8 Hz, 1H), 7.41 (dt, J=8.2, 1.1 Hz, 1H), 7.21 (ddd, J=9.0, 8.4, 1.1 Hz, 1H). LCMS (Method C): RT=3.90 min, m/z: 299 [M+H+].

Provenance & Evidence