Hydrochloric Acid → (2-Bromo-pyridin-4-yl)-[5-(4-dimethylamino-piperidin-1-yl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-benzoimidazol-2-yl]-methanone

Participants

Reaction Conditions

Reaction Steps

(2-Bromo-pyridin-4-yl)-[5-(4-dimethylamino-piperidin-1-yl)-1H-benzoimidazol-2-yl]-methanone (11.9 g, 27.8 mmol) was dissolved in 200 mL of dry THF. This solution was cooled at 0° C. and NaH 60% dispersion (1.34 g, 33.3 mmol) was added in portions. The mixture stirred at 0° C. for 30 minutes and then the 2-(trimethylsilyl)ethoxymethyl chloride (5.56 g, 33.3 mmol) was added dropwise. The mixture was allowed to warm at room temperature while stirring overnight. 2M Aqueous HCl (300 mL) was carefully added and then the aqueous mixture was washed with EtOAc (3×100 mL). The aqueous phase was then neutralised with saturated aqueous NaHCO3 and then extracted with CHCl3/iPrOH (3:1; 3×250 mL). The combined CHCl3/i-PrOH fractions were dried (Na2SO4) and then evaporated to dryness. Purification by SiO2 chromatography (dichloromethane/NH3 2.0M in MeOH; 98:2 to 90:10) gave the title compound as a dark red oil (11.2 g, yield 72%; as a mixture of two regioisomers). MS(ESI) m/z 558, 560.2 (M+H)+.

Provenance & Evidence