反应详情

温度

40 °C

To the crude reaction mixture from Step 2 was added 2.0 M of dimethylamine in tetrahydrofuran (0.15 mL). The resulting mixture was then stirred at 40° C. After 1.5 hours, 2.0 M of dimethylamine in tetrahydrofuran (0.20 mL), triethylamine (0.05 mL, 0.4 mmol), and 1 mL N,N-dimethylformamide were added and the reaction mixture was heated at 50° C. After an additional hour, the reaction was poured into dichloromethane and washed once with saturated aqueous NaHCO3, dried over MgSO4, filtered, and evaporated in vacuo. The crude product was purified via reverse phase HPLC and lyophilized to yield 17.6 mg (22%) of N-(3-(3-(cyclopropanecarboxamido)isoquinolin-7-yl)-4-methylphenyl)-4-(1-(dimethylamino)ethyl)benzamide. LCMS (ESI): RT (min)=4.090, M+H=493.2, method=E; 1H NMR (400 MHz, DMSO-d6) δ 10.90 (s, 1H), 10.20 (s, 1H), 9.19 (s, 1H), 8.50 (s, 1H), 8.02 (s, 1H), 7.92 (overlapping, 3H), 7.79 (d, J=1.9 Hz, 1H), 7.77-7.67 (m, 2H), 7.44 (d, J=8.2 Hz, 2H), 7.32 (d, J=8.4 Hz, 1H), 3.35 (q, J=6.8 Hz, 1H), 2.26 (s, 3H), 2.11 (s, 7H), 1.29 (d, J=6.7 Hz, 3H), 0.85 (m, 4H).

1. temperaturethe reaction mixture was heated at 50° C
2. waitAfter an additional hour
3. washwashed once with saturated aqueous NaHCO3
4. dry with materialdried over MgSO4
5. filtrationfiltered
6. customevaporated in vacuo
7. customThe crude product was purified via reverse phase HPLC