Lithium Hexamethyldisilazide → [4-(3-Chloro-pyrazin-2-yloxy)-phenyl]-(6-fluoro-1H-benzoimidazol-2-YL)-methanone

Participants

Reaction Steps

A solution of 4-(3-Chloro-pyrazin-2-yloxy)-benzoic acid ethyl ester (20 g, 84.7 mmol) and 6-fluoro benzoimidazole-1-carboxylic acid tert-butyl ester (21.2 g, 76.3 mmol) in freshly dried THF (150 mL) was cooled to −78° C. LiHMDS (106 mL, 106 mmol) was added slowly to it over 1.2 h. The reaction mixture was stirred at the same temperature for 3.5 h. The reaction was brought to −20° C. and slowly quenched with addition of 2N HCl until pH 3-4. The resulting mixture was stirred at RT for 1 h, extracted with ethyl acetate (3×200 mL), and washed with water (2×100 mL). The organic layer was dried (Na2SO4) and concentrated. To the crude product was added methanol (70 mL). After stirring for 1 h, the solid was collected by filtration to give the title compound. MS (ESI, pos. ion) m/z: 369.2 (M+1). IC50 (uM) +.

Provenance & Evidence