反应详情

Following procedures essentially as described in Example 219, mix 11-bromomethylene-3,8-difluoro-6,11-dihydro-dibenzo[b,e]oxepine (E-isomer, 40 mg, 0.12 mmol), 1-(2-morpholin-4-yl-ethyl)-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1,3-dihydro-benzoimidazol-2-one (44 mg, 0.12 mmol), Na2CO3 (2M in water, 155 μL, 0.310 mmol), dioxane (1 mL), and Pd(PPh3)4 (7 mg, 0.006 mmol). Purify on silica gel (12 g), eluting with 2% to 5% (2M NH3/MeOH)/CH2Cl2 to afford 45 mg (78%) of the title compound as a white foam. HPLC (ISO80-10) t=1.86 min, 99%; MS [ES] 488 (M−H), 490 (M+H); 1H-NMR (DMSO-d6) δ 10.70 (s, 1H), 7.59 (dd, 1H, J=8.5, 7.1 Hz), 7.51 (dd, 1H, J=8.8, 2.6 Hz), 7.08 (td, 1H, J12.5, 4.3 Hz), 7.01 (m, 2H), 6.96 (d, 1H, J=7.9 Hz), 6.80 (td, 1H, J=12.0, 4.2 Hz), 6.73 (d, 1H, J=7.9 Hz), 6.62 (dd, 1H, J=10.3, 2.4 Hz), 6.58 (s, 1H), 5.72-4.85 (br d, 2H), 3.81 (t, 2H, J=6.4 Hz), 3.47 (t, 4H, J=4.4 Hz), 2.48 (m, 2H), 2.38 (s, 4H).

1. customPurify on silica gel (12 g)
2. washeluting with 2% to 5% (2M NH3/MeOH)/CH2Cl2