tert-Butanol → HCID 59013889, compound

Participants

Reaction Steps

To a solution of 4-(4-chloro-[1,2,5]thiadiazol-3-yl)-piperazine-1-carboxylic acid (3,5-bis-trifluoromethyl-phenyl)-amide (103.7 mg, 0.226 mmol, prepared in Example 10b) and 1M solution of potassium tert-butoxide in tert-butanol (0.70 mL, 0.70 mmol) was added 2-chloro-4-pyridinemethanol (64.5 mg, 0.448 mmol, prepared in Example 16a). The resulting suspension was stirred at room temperature for 2 h. The crude reaction mixture was diluted with methanol and purified by preparative HPLC (0.1% TFA in water, 0.1% TFA in acetonitrile). The pure fractions were combined and the acetonitrile/TFA was removed in vacuo. The remaining aqueous solution was made basic with NaHCO3 and the free based product was extracted into EtOAc. The organic phase was concentrated in vacuo yielding pure product N-[3,5-bis(trifluoromethyl)phenyl]-4-(4-{[(2-chloropyridin-4-yl)methyl]oxy}-1,2,5-thiadiazol-3-yl)piperazine-1-carboxamide (33.4 mg, 26.1% yield). 1H NMR (CDCl3) 8.43 (d, 1H), 7.90 (s, 2H), 7.55 (s, 1H), 7.38 (s, 1H), 6.68 (s, 1H), 5.49 (s, 2H), 3.66 (d, 8H) ppm.

Provenance & Evidence