反应详情

温度

70 °C

Compound 258 (0.100 g, 0.20 mmol) was suspended in dioxane (4.8 mL) and methanol (4.8 mL). A solution of lithium hydroxide, monohydrate (0.0092 g, 0.22 mmol) in 2.0 mL of water was added to the suspension. The reaction was warmed to 70° C. After 1 hour, solvent was removed in vacuo. The residue was dissolved in water (3 mL). Dichloromethane was added (1 mL) and the pH was brought to ca. pH 10 with dilute NaOH. The organics were removed and the aqueous was brought to ca. pH 4 with dilute HCl. The resulting precipitate was filtered. Purification by RP-HPLC on C18 column (10-90% CH3CN in water with 0.1% TFA) provided compound 259 (5 mg) as a TFA salt. 1H NMR (500 MHz, DMSO-d6) δ 1.28-1.41 (m, J=12.17, 12.01, 12.01, 3.18 Hz, 2 H) 1.68-1.94 (m, 5 H) 1.99-2.09 (m, 2 H) 2.09-2.19 (m, 2 H) 2.21-2.34 (m, 4 H) 2.81 (t, 11.49 Hz, 2 H) 3.71 (d, J=12.23 Hz, 2 H) 5.53 (quin, J=9.11 Hz, 1 H) 7.72 (d, J=9.05 Hz, 1 H) 7.98 (br. s., 1 H) 8.06 (d, J=8.56 Hz, 1 H) 8.11-8.18 (m, 1 H) 8.25 (dd, J=4.65, 2.93 Hz, 1 H) 9.51 (s, 1 H) 11.43 (br. s., 1 H) ppm. LCMS-ESI (POS), M/Z, M+1: Found 490.1, Calculated 490.2.

1. customsolvent was removed in vacuo
2. dissolutionThe residue was dissolved in water (3 mL)
3. additionDichloromethane was added (1 mL)
4. customThe organics were removed
5. filtrationThe resulting precipitate was filtered
6. customPurification by RP-HPLC on C18 column (10-90% CH3CN in water with 0.1% TFA)