反应详情

温度

110 °C

A sealed tube equipped with a magnetic stirrer was charged with (4-fluoro-2-{6-oxo-8-thia-4,5-diazatricyclo[7.4.0.02,7]trideca-1(9),2(7),3-trien-5-yl}-6-(tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)methyl acetate (200 mg, 0.44 mmol), 6-chloro-N-(5-(4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-yl)imidazo[1,2-b]pyridazin-8-amine 105a (155 mg, 0.44 mmol), tricyclohexylphosphine (112 mg, 0.4 mmol), Pd2(dba)3 (28 mg, 0.024 mmol), Cs2CO3 (261 mg, 0.8 mmol), and dioxane (25 mL). After three cycles of vacuum/argon flush, the reaction mixture was heated at 110° C. for 16 h. The mixture was evaporated in vacuo and the residue was extracted with ethyl acetate (10 mL×2). The combined ethyl acetate extract was concentrated under reduced pressure and the residue was purified with reverse-phase prep-HPLC to afford 112 (26 mg, 12%). MS: [M+H]+ 680. 1H NMR (500 MHz, DMSO) δ 9.95 (s, 1H), 8.49 (s, 1H), 8.24 (s, 1H), 8.17 (s, 1H), 8.04 (s, 1H), 7.67 (s, 1H), 7.45-7.53 (m, 4H), 4.54-4.57 (m, 3H), 4.45-4.47 (m, 2H), 4.33 (d, J=12.5, 2H), 3.35-3.46 (m, 1H), 3.13-3.17 (m, 4H), 2.83-2.94 (m, 4H), 2.47-2.50 (m, 4H), 1.82-1.87 (m, 4H)

1. customA sealed tube equipped with a magnetic stirrer
2. customAfter three cycles of vacuum/argon flush
3. customThe mixture was evaporated in vacuo
4. extractionthe residue was extracted with ethyl acetate (10 mL×2)
5. extractionThe combined ethyl acetate extract
6. concentrationwas concentrated under reduced pressure
7. customthe residue was purified with reverse-phase prep-HPLC