反应详情

温度

25 °C

In a 250 mL round-bottomed flask, 2-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-6-(5-(5-(4-hydroxy-4-methylpiperidine-1-carbonyl)pyridin-2-ylamino)-1-methyl-6-oxo-1,6-dihydropyridazin-3-yl)benzyl acetate (62 mg, 87.4 μmol) was combined with dioxane (5 ml) and 1M LiOH (1 ml) to give a brown solution. The reaction mixture was stirred at 25° C. for 5 h. The crude reaction mixture was concentrated in vacuo and partitioned between DCM and water. The aqueous layer was back-extracted with DCM (2×25 mL). The organic layers were combined, washed with sat NaCl (1×10 mL), dried over Na2SO4 and concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, 24 g, 0% to 8% MeOH in DCM), isolated as an off-white powder and dried under vacuum for 3 hrs at 25° C. The material was repurified by flash chromatography (silica gel, 24 g, 0% to 4% MeOH in DCM) to afford 0.008 g (14%) of the title compound as a white solid. (M+H)+=668 m/e. 1H NMR (300 MHz, CHLOROFORM-d) δ: 8.69 (s, 1H), 8.39-8.47 (m, 2H), 8.29 (d, J=2.3 Hz, 1H), 7.75 (dd, J=8.5, 2.1 Hz, 1H), 7.43-7.70 (m, 5H), 6.99 (d, J=8.7 Hz, 1H), 4.43 (br. s., 2H), 3.91 (s, 3H), 3.20-3.87 (m, 4H), 1.65 (br. s., 6H) 1.43 (s, 9H).

1. customto give a brown solution
2. customThe crude reaction mixture
3. concentrationwas concentrated in vacuo
4. custompartitioned between DCM and water
5. extractionThe aqueous layer was back-extracted with DCM (2×25 mL)
6. washwashed with sat NaCl (1×10 mL)
7. dry with materialdried over Na2SO4
8. concentrationconcentrated in vacuo
9. customThe crude material was purified by flash chromatography (silica gel, 24 g, 0% to 8% MeOH in DCM)
10. customisolated as an off-white powder
11. customdried under vacuum for 3 hrs at 25° C
12. customThe material was repurified by flash chromatography (silica gel, 24 g, 0% to 4% MeOH in DCM)