反应详情

温度

50 °C

A solution of Example 418C (145.6 mg, 0.404 mmol) in THF (0.25 mL) was treated with carbonyldiimidazole (65.5 mg, 0.404 mmol), heated to 50° C. for 1.5 hours, cooled to room temperature, treated with 2-(2-aminoethyl)-1-methylpyrrolidine. (58 μL, 0.404 mmol), stirred for 24 hours, and concentrated. The residue was dissolved in pyridine (0.5 mL), treated with LiI (162.2 mg, 1.212 mmol), heated in a microwave reactor at 150° C. for 25 minutes, concentrated, and purified by C18 reverse-phase HPLC using acetonitrile/water/0.1% TFA to provide the desired product. (58.7 mg, 29%). MS (ESI(−)) m/e 499 (M−H)-; 1H NMR (300 MHz, DMSO-d6) δ 9.74 (s, 1H), 8.21 (m, 1H), 7.66 (dd, 1H), 7.53 (ddd, 1H), 7.32 (t, 1H), 7.07 (td, 1H), 6.96 (d, 1H), 6.53 (d, 1H), 3.18 (m, 3H), 3.01 (m, 2H), 2.78 (s, 3H), 2.66 (m, 4H), 2.30 (m, 2H), 1.92 (m, 2H), 1.67 (m, 4H), 1.28 (m, 1H), 0.87 (m, 1H).

1. temperaturecooled to room temperature
2. concentrationconcentrated
3. dissolutionThe residue was dissolved in pyridine (0.5 mL)
4. temperatureheated in a microwave reactor at 150° C. for 25 minutes
5. concentrationconcentrated
6. custompurified by C18 reverse-phase