反应详情

A mixture of (1S,2S)-2-fluoro-N-(7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)isoquinolin-3-yl)cyclopropanecarboxamide (56.5 mg; 0.159 mmol), (3-bromo-4-methylpyridin-2-yl)methanol (75 mg; 0.37120 mmol), bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II) (9.1 mg; 0.013 mmol), potassium carbonate (65.2 mg; 0.472 mmol), dioxane (2.0 mL; 23 mmol), and water (0.2 mL; 10 mmol) was subjected to microwave irradiation at 100° C. for 60 minutes. The reaction mixture was diluted with ethyl acetate, washed with water and brine, dried over magnesium sulfate, filtered, and evaporated in vacuo. The crude reaction mixture was purified via reverse-phase preparatory HPLC and lyophilized to yield 3.9 mg (7%) of the title compound. LCMS (ESI): RT (min)=2.16, M+H=352.2, method=H; 1H NMR (400 MHz, DMSO) δ 10.96 (s, 1H), 9.15 (s, 1H), 8.53 (s, 1H), 8.48 (d, J=5.0 Hz, 1H), 7.97 (d, J=8.5 Hz, 1H), 7.94 (s, 1H), 7.57 (d, J=8.4 Hz, 1H), 7.34 (d, J=5.0 Hz, 1H), 4.95 (m, 2H), 4.25 (s, 2H), 2.28 (m, 1H), 2.07 (s, 3H), 1.77-1.61 (m, 1H), 1.28-1.12 (m, 1H).

1. customirradiation at 100° C. for 60 minutes
2. washwashed with water and brine
3. dry with materialdried over magnesium sulfate
4. filtrationfiltered
5. customevaporated in vacuo
6. customThe crude reaction mixture
7. customwas purified via reverse-phase preparatory HPLC