反应详情

温度

50 °C

To N-((2,2-dimethyl-1,3-dioxolan-4-yl)methyl)-5-(5-phenyl-4-((pyridin-2ylmethyl)amino)phthalazin-1-yl)nicotinamide (0.0200 g, 0.0370 mmol) was added TFA (0.00282 mL, 0.0370 mmol) at room temperature and was heated at 50° C. for 4 h. TFA was removed under reduced pressure and reaction mixture was diluted with saturated NaHCO3 (50 mL). The reaction mixture was extracted with EtOAc (3×30 mL). The combined organic extracts were dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The resulting residue was purified by preparative HPLC (Condition 14 as described in general methods) to afford N-(2,3-dihydroxypropyl)-5-(5-phenyl-4-((pyridin-2-ylmethyl)amino)phthalazin-1-yl)nicotinamide (0.0120 g, 65%). LCMS (Condition 7): retention time 1.59 min, [M+1]=507.2. HPLC (Condition 25): retention time 5.23 min, Purity 97.90%. 1H NMR (400 MHz, DMSO-d6) δ 3.21-3.49 (m, 4 H), 3.63-3.72 (m, 1 H), 4.55-4.60 (m, 1 H), 4.66 (d, J=4.0 Hz, 2 H), 4.84 (br s, 1 H), 6.32 (dd, J=4.0 Hz, J=4.4 Hz, 1 H), 7.22 (dd, J=4.8 Hz, J=6.8 Hz, 1 H), 7.28 (d, J=8.0 Hz, 1 H), 7.50-7.58 (m, 5 H), 7.68-7.73 (m, 2 H), 7.80 (dd, J=1.6 Hz, J=8.4 Hz, 1 H), 7.93 (dd, J=7.2 Hz, J=8.4 Hz, 1 H), 8.23 (d, J=4.8 Hz, 1 H), 8.51 (t, J=2.0 Hz, 1 H), 8.75 (t, J=5.6 Hz, 1 H), 8.98 (d, J=2.0 Hz, 1 H), 9.16 (d, J=2.0 Hz, 1 H).

1. customTFA was removed under reduced pressure and reaction mixture
2. additionwas diluted with saturated NaHCO3 (50 mL)
3. extractionThe reaction mixture was extracted with EtOAc (3×30 mL)
4. dry with materialThe combined organic extracts were dried over anhydrous Na2SO4
5. filtrationfiltered
6. concentrationconcentrated under reduced pressure
7. customThe resulting residue was purified by preparative HPLC (Condition 14 as described in general methods)