Sodium hydride → 7-(4-methyl-1H-imidazol-1-yl)-5-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)imidazo[1,2-c]pyrimidine

Beteiligte Stoffe

Reaktionsschritte

To a flask charged with 4-methyl-1H-imidazole (0.117 g, 1.43 mmol) and 1 mL of N,N-dimethylformamide was added sodium hydride (60% in oil dispersion) (0.0514 g, 1.29 mmol) at 0° C. with stirring. The reaction mixture was then placed under nitrogen and allowed to warm to ambient temperature and stirred for 30 minutes. To the reaction was added 7-chloro-5-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)imidazo[1,2-c]pyrimidine (Preparation G; 0.100 g, 0.286 mmol) and argon was bubbled through the reaction for 5 minutes. The reaction was sealed and heated to 100° C. The reaction was diluted with dichloromethane (50 mL) and 5 mL of aqueous saturated sodium bicarbonate was added. The reaction mixture was stirred for 20 minutes, then concentrated to dryness under reduced pressure at 50° C. and dried on high vacuum overnight. The crude material was taken up in 1:1 ethyl acetate: dichloromethane with 5% methanol (100 mL) and sonicated for 1 hour. This suspension was filtered, the cake was washed with EtOAc (50 mL) and the rinse was then concentrated under reduced pressure. The resulting residue was purified by silica gel chromatography eluting with 1% methanol in dichloromethane containing 0.5% ammonium hydroxide to obtain 7-(4-methyl-1H-imidazol-1-yl)-5-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)imidazo[1,2-c]pyrimidine (0.053 g, 0.077 mmol, 27% yield). MS (apci) m/z=396.2 (M+H).

Herkunft & Nachweise