反应详情

温度

55 °C

A mixture of Example 476D (20 mg, 0.05 mmol) in DMF (1.0 mL) was treated with macroporous polystyrene bound DCC resin (105 mg, 0.14 mmol), 1-hydroxybenzotriazole hydrate (7 mg, 0.05 mmol), diisopropylethylamine (0.026 mL, 0.15 mmol) and 2-(aminoethyl)-1-methylpyrrolidine (0.010 mL, 0.07 mmol), heated to 55° C. for 16 hours, and concentrated. The concentrate was dissolved in 0.5 mL 2:1 dioxane/water, treated with LiOH (13 mg, 0.3 mmol), and heated to 160° C. for 27.5 minutes in a microwave reactor. The reaction mixture was concentrated and the residue was purified by C18 reverse-phase HPLC using acetonitrile/water/0.1% TFA to provide the desired product. MS (DCI) m/e 512 (M+H)+; 1H NMR (500 MHz, DMSO-d6) δ 12.89 (br s, 1H), 9.37 (br s, 1H), 7.99 (t, 1H), 7.61 (d, 2H), 7.54 (t, 1H), 7.46-7.43 (m, 3H), 7.31 (s, 1H), 6.28 (d, 1H), 3.23 (m, 4H), 3.08 (m, 1H), 2.84 (d, 3H), 2.75 (m, 2H), 2.65 (m, 2H), 2.30 (m, 1H), 2.04 (m, 2H), 1.90 (m, 1H), 1.71-1.63 (m, 6H).

1. concentrationconcentrated
2. dissolutionThe concentrate was dissolved in 0.5 mL 2:1 dioxane/water
3. temperatureheated to 160° C. for 27.5 minutes in a microwave reactor
4. concentrationThe reaction mixture was concentrated
5. customthe residue was purified by C18 reverse-phase