Hydrochloric Acid → 4-chloro-6-(5-isopropyl-2-methylphenyl)-2-(3-methyl-1-tosyl-1H-indol-4-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine

Participants

Reaction Conditions

Reaction Steps

Ethanol (4 mL) was added to 6-(5-isopropyl-2-methylphenyl)-4-methoxy-2-(3-methyl-1-tosyl-1H-indol-4-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine (0.92 g, 1.58 mmol) and then 12 N aqueous HCl (2 mL, 24 mmol) was added and the mixture was heated to 68° C. for ca. 15 hours. The reaction was then cooled to room temperature, diluted with dichloromethane, and neutralized via the slow addition of saturated aqueous sodium bicarbonate. The resulting layers were separated and the aqueous layer was extracted two additional times with dichloromethane. The organic layers were combined, dried over Na2SO4, filtered, and concentrated. The resulting residue was then dissolved in dichloromethane (20 mL) and cooled to 0° C. and N-chloromethylene-N,N-dimethyl ammonium chloride (Vilsmeier reagent) (0.41 g, 3.21 mmol) was added. The reaction was then placed at room temperature for 25 minutes. The reaction was then diluted with dichloromethane and saturated aqueous sodium bicarbonate. The resulting layers were separated and the aqueous layer was extracted one additional time with dichloromethane. The organic layers were combined, dried over Na2SO4 filtered and concentrated. The resulting residue was purified by silica gel flash chromatography (0-45% ethyl acetate/heptanes) to provide 4-chloro-6-(5-isopropyl-2-methylphenyl)-2-(3-methyl-1-tosyl-1H-indol-4-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine. MS (ESI+) m/z 585.2 (M+H)+.

Provenance & Evidence