反应详情
EQUATION
反应方程式
REACTANTS
反应物
PRODUCTS
生成物
CONDITIONS
反应条件
- 温度
- 70 °C
PROCEDURE
实验过程
A mixture of methyl 2-(6-([1,1′-biphenyl]-3-yl)-4-(4-fluorophenyl)-2-isopropyl-8,8-dimethyl-5,6,7,8-tetrahydro-1,6-naphthyridin-3-yl)-2-(tert-butoxy)acetate (intermediate 8) (10 mg, 0.017 mmol), lithium hydroxide monohydrate (2.12 mg, 0.05 mmol) and 1N NaOH (0.17 mL) were stirred at 70° C. for 16 h. The mixture was then filtered and purified by preparative HPLC (10% CH3CN/90% H2O/0.1% CF3CO2H, Xterra 19×100 mm, C18, 5 μm column) to give 2-(6-([1,1′-biphenyl]-3-yl)-4-(4-fluorophenyl)-2-isopropyl-8,8-dimethyl-5,6,7,8-tetrahydro-1,6-naphthyridin-3-yl)-2-(tert-butoxy)acetic acid (4.2 mg, 41% yield) as a white solid. 1H NMR (500 MHz, CD3OD) δ ppm 7.62-7.47 (m, 3H), 7.46-7.38 (m, 3H), 7.38-7.29 (m, 3H), 7.26 (t, J=7.9 Hz, 1H), 7.02 (d, J=7.3 Hz, 1H), 6.96 (s, 1H), 6.77 (dd, J=8.2, 1.5Hz, 1H), 4.92 (d, br. s., 1H), 4.07 (d, J=15.6 Hz, 1H), 3.71 (d, J=15.6 Hz, 1H), 3.63 (dt, J=12.8, 6.4 Hz, 1H), 3.49 (d, J=12.5Hz, 1H), 3.37 (br. s., 1H), 1.48 (d, J=3.7 Hz, 6H), 1.32 (d, J=6.4 Hz, 3H), 1.20 (d, J=6.7 Hz, 3H), 1.01 (s, 9H). 19F NMR (500 MHz, CD3OD) δ ppm −115.74. LCMS (M+H) calcd for C37H42FN2O3: 581.3. found: 581.5.
WORKUP
后处理
- filtrationThe mixture was then filtered
- custompurified by preparative HPLC (10% CH3CN/90% H2O/0.1% CF3CO2H, Xterra 19×100 mm, C18, 5 μm column)