Water → (S)-6-(5-isopropyl-2-methylphenyl)-4-(4-methoxy-3,3-dimethylpiperidin-1-yl)-2-(3-methyl-1H-indol-4-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine

Participants

Reaction Conditions

Reaction Steps

To a solution of (S)-6-(5-isopropyl-2-methylphenyl)-4-(4-methoxy-3,3-dimethylpiperidin-1-yl)-2-(3-methyl-1-tosyl-1H-indol-4-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine (135 mg, 0.195 mmol) in methanol (2 mL) in a microwave vial was added KOH (100 mg, 1.75 mmol) followed by 28% ammonium hydroxide in water (1 mL, 7.25 mmol). The vial was sealed and heated via microwave irradiation at 80° C. for 75 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 (0-70% ethyl acetate/heptanes) to furnish (S)-6-(5-isopropyl-2-methylphenyl)-4-(4-methoxy-3,3-dimethylpiperidin-1-yl)-2-(3-methyl-1H-indol-4-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine. 1H NMR (400 MHz, DMSO-d6) δ ppm 0.92 (s, 3 H) 0.98 (s, 3 H) 1.18 (d, J=6.8 Hz, 6 H) 1.51-1.62 (m, 1 H) 1.91-1.99 (m, 1 H) 2.01 (s, 3 H) 2.21 (s, 3 H) 2.78-2.88 (m, 2 H) 2.91-3.08 (m, 4 H) 3.29 (s, 3 H) 3.31-3.41 (m, 3 H) 3.60-3.71 (m, 1 H) 4.07 (s, 2 H) 6.86 (d, J=7.3 Hz, 1 H) 6.96 (s, 1 H) 7.07-7.15 (m, 3 H) 7.20 (d, J=7.1 Hz, 1H) 7.41 (d, J=7.8 Hz, 1 H) 10.89 (br. s., 1 H); MS (ESI+) m/z 538.4 (M+H)+.

Provenance & Evidence