Acetic Acid → HCID 86687530, compound

Participants

Reaction Steps

To a flask containing an ice cold suspension of N-(4-methoxybenzyl)thiazol-2-amine (40.2 mg, 0.182 mmol) in THF (668 μl) was added lithium bis(trimethylsilyl)amide (1M in THF) (191 μl, 0.191 mmol) drop wise over 10 min. The mixture was stirred for 15 min prior to the drop wise addition of a solution of 4-(2-methoxy-4-(trifluoromethyl)phenyl)cinnoline-7-sulfonyl chloride (70 mg, 0.174 mmol) in THF (0.7 ml). The solution was allowed to stir for 1 hr (ice melt) providing a brown solution. To the mixture was added acetic acid (about 100 μl) and the mixture dried under reduced pressure. To the crude material was added DCM (1 ml) followed by TFA (0.3 ml) and the mixture stirred at room temperature for 2 hrs. The mixture was dried under reduced pressure and the crude material purified with a 25 g spherical silica column (15 μm spherical, Interchim) ramping EtOAc in heptane (0 to 70%, 10% DCM isocratic throughout) providing product which was lyophilized from MeOH/H2O to afford 4-(2-methoxy-4-(trifluoromethyl)phenyl)-N-(thiazol-2-yl)cinnoline-7-sulfonamide (34 mg, 0.073 mmol, 41.9% yield) as a light yellow solid. 1H NMR (400 MHz, DMSO-d6) μ ppm 3.79 (s, 3H) 6.91 (d, J=4.50 Hz, 1H) 7.32 (d, J=4.60 Hz, 1H) 7.51-7.60 (m, 2H) 7.66 (d, J=7.53 Hz, 1H) 7.77-7.84 (m, 1H) 8.08 (dd, J=8.90, 1.86 Hz, 1H) 8.87 (dd, J=1.81, 0.54 Hz, 1H) 9.45 (s, 1H) 13.03 (br. s., 1H). m/z (ESI) 467.2 (M+H)+.

Provenance & Evidence