Potassium Hydroxide → HCID 71240555, compound

Participants

Reaction Steps

To a solution of 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, prepared as described in Example 17 (110 mg, 0.188 mmol) in methanol (5 mL) was added 25% sodium methoxide in methanol (40.6 mg, 0.188 mmol). The reaction was stirred for ca. 40 minutes at room temperature at which time the mixture was diluted with EtOAc and water. The layers were separated, and the organic layer was washed with brine, dried over Na2SO4, filtered, and concentrated. The resulting residue was added to a microwave vial, and diluted with EtOH (2 mL) and charged with KOH (ca. 100 mg, 1.75 mmol) and 28% ammonium hydroxide in water (1 mL, 7.25 mmol). The vial was sealed and heated via microwave irradiation at 100° C. for 45 minutes. The reaction mixture was cooled to room temperature and diluted with dichloromethane and brine. The 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 purified by silica gel flash chromatography (0-100% ethyl acetate/heptanes) and then further purified by reverse phase HPLC (20-100% MeCN/0.1% NH4OH in water to afford 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.

Provenance & Evidence