反应详情

To a solution of the TFA salt of 2-(2,6-dimethylphenyl)-4-((trans)-2,5-dimethylpiperazin-1-yl)-6-(5-isopropyl-2-methylphenyl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine TFA salt (0.113 g, 0.233 mmol), DIEA (0.33 mL, 1.87 mmol) and DCM (5 mL) was added Ac2O (0.044 mL, 0.467 mmol). The reaction was stirred at rt for 1 h before being diluted with EtOAc. The solution was washed with sat aq NaHCO3 and then brine before the organic layers were separated and then dried (Na2SO4), filtered and concentrated. The residue was then purified by FCC (35-45% EtOAc/heptane) to give racemic-1-(4-(2-(2,6-dimethylphenyl)-6-(5-isopropyl-2-methylphenyl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-yl)-(trans)-2,5-dimethylpiperazin-1-yl)ethanone. 1H NMR (400 MHz, DMSO-d6, at 100° C.) δ ppm 7.14-7.19 (m, 1 H) 7.05-7.12 (m, 3 H) 6.91 (d, J=1.39 Hz, 1 H) 6.86 (dd, J=7.71, 1.52 Hz, 1 H) 4.29 (dt, J=6.22, 3.27 Hz, 1 H) 4.12-4.18 (m, 1 H) 4.00-4.07 (m, 1 H) 3.50-3.58 (m, 1 H) 3.41-3.47 (m, 1 H) 3.39 (t, J=6.19 Hz, 2 H) 2.93 (br. s., 4 H) 2.84 (dt, J=13.80, 6.93 Hz, 1 H) 2.52 (br. s., 1 H) 2.25 (s, 3 H) 2.08 (s, 6 H) 2.01 (s, 3 H) 1.19 (dd, J=6.95, 2.40 Hz, 6 H) 1.10-1.17 (m, 6 H); MS (ESI+) m/z 526.4 (M+H)+.

1. washThe solution was washed with sat aq NaHCO3
2. custombrine before the organic layers were separated
3. dry with materialdried (Na2SO4)
4. filtrationfiltered
5. concentrationconcentrated
6. customThe residue was then purified by FCC (35-45% EtOAc/heptane)