Trimethylsilyl cyanide → HCID 16743582, compound

Participants

Reaction Steps

At 0° C. to a solution of N-((5-chloropyridin-2-yl)(3-fluoro-5-(trifluoromethyl)phenyl)methylene)-4,5-dimethylthiazol-2-amine (848 mg, 2.05 mmol) in MeOH (10 mL) was added ZnCl2 (214 mg, 1.43 mmol), followed by the addition of TMSCN (830 μL, 6.19 mmol). The reaction was allowed to slowly warm up to room temperature and heated at 65° C. for 18 h. The reaction mixture was cooled down to room temperature and concentrated. The residue was diluted by addition of DCM. The solid was removed by filtration and the filtrate was concentrated. A portion of the residue was purified by ISCO chromatography (12 g column) using hexanes/EtOAc (0-300%) over 22 min. Methyl 2-(5-chloropyridin-2-yl)-2-(4,5-dimethylthiazol-2-ylamino)-2-(3-fluoro-5-(trifluoromethyl)phenyl)acetate eluted at a retention time of 7-8 min. LCMS RT=3.25 min [M+H] 473.84 (Phenomenex Luna C18 column, 4.6×50 mm eluting with 10-90% MeOH/H2O over 4 minutes containing 0.1% TFA; 4 mL/min, monitoring at 220 nm). NMR: 400 MHz 1H (CDCl3) 7.74 ppm, 1H, s; 7.67 ppm, 1H, dd, J=8.57, 2.42 Hz; 7.56 ppm, 1H, m; 7.30 ppm, 2H, m; 3.76 ppm, 3H, m; 2.09 ppm, 6H, m.

Provenance & Evidence