Sodium hydride → 2-[1-[9-Chloro-1-(2,4-dichlorophenyl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazol-6-yl]propoxy]ethanol

Participants

Reaction Steps

To a solution of 1-[9-chloro-1-(2,4-dichlorophenyl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazol-6-yl]propan-1-ol (150.0 mg, 0.365 mmol) in N,N-dimethylformamide (1.5 mL) was added sodium hydride (23.4 mg, 0.584 mmol) at 0° C. After 30 min, to the mixture was added (2-bromomethoxy)-tert-butyldimethylsilane (0.39 mL, 1.83 mmol). The reaction mixture was stirred at room temperature for 3 hrs. The mixture was quenched with aqueous saturated ammonium chloride and extracted with ethyl acetate (×3). The combined organic layer was washed with water (×2) and brine (×1), dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo. The residue was purified by silica gel column chromatography eluting with a 0-50% ethyl acetate/n-hexane gradient mixture. To a solution of silyl ether (76.3 mg, 0.134 mmol) in tetrahydrofuran (1.0 mL) was added tetrabutylammonium fluoride (1.0 M solution in tetrahydrofuran, 0.27 mL, 0.268 mmol) at 0° C. The reaction mixture was stirred at room temperature for 2 hrs. The starting material wasn't consumed completely. To the mixture was added tetrabutylammonium fluoride (1.0 M solution in tetrahydrofuran, 0.13 mL, 0.134 mmol) at 0° C. The reaction mixture was stirred at room temperature for 2 hrs. The mixture was quenched with aqueous saturated ammonium chloride and extracted with ethyl acetate (×3). The combined organic layer was washed with brine (×1), dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo. The residue was purified by silica gel column chromatography eluting with a 0-50% ethyl acetate/n-hexane gradient mixture to give the title compound as an amorphous (35.6 mg, 0.0783 mmol, 21% (2 steps)).

Provenance & Evidence