Reaction Steps
To a suspension of Example 412C (150 mg, 0.31 mmol) in DMF (3 mL) was added 4-hydroxypiperidine (63 mg, 0.62 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (120 mg, 0.62 mmol), HOBt (84 mg, 0.62 mmol) and triethylamine (87 μL, 0.62 mmol) at room temperature. The mixture was stirred at the same temperature for 15 h. Ethyl acetate was added, the mixture was washed with brine, water, and was concentrated. The residual oil was dissolved in THF (3 mL), and was treated with lithium hydroxide monohydrate (26 mg, 0.62 mmol) in water (1.5 mL). After stirring for 15 hours, the solution was separated by HPLC (Zorbax C-18) to give the title compound (132 mg, 55%). 1H NMR (300 MHz, DMSO-d6) δ 1.32 (m, 2H), 1.65 (m, 2H), 1.75 (m, 2H), 1.92 (m, 2H), 2.43 (m, 1H), 2.86 (t, J=10.6 Hz, 2H), 3.15 (m, 1H), 3.32 (m, 1H), 3.71 (m, 3H), 3.95 (m, 2H), 6.73 (d, J=8.5 Hz, 1H), 6.94 (d, J=7.2 Hz, 1H), 7.13 (d, J=7.8 Hz, 1H), 7.13 (s, 1H), 7.24 (d, J=15.2 Hz, 1H), 7.37 (t, J=8.1 Hz, 1H), 7.72 (d, J=15.2 Hz, 1H), 7.85 (d, J=8.5 Hz, 1H); MS (ESI+) m/z 535, 537 (M+H)+. Anal. calcd for C26H28N2Cl2SO4 0.25 TFA: C, 56.43; H, 5.05; N, 4.97. Found: C, 56.37; H, 5.00; N, 4.91.
