Reaction Steps
Following procedures essentially as described in Example 219, mix 11-bromomethylene-3,8-difluoro-6,11-dihydro-dibenzo[b,e]oxepine (E-isomer, 326 mg, 1.0 mmol), 5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1,3-dihydro-benzoimidazol-2-one (250 mg, 0.961 mmol), Na2CO3 (2M in water, 1.20 mL, 2.40 mmol), dioxane (7 mL), and Pd(PPh3)4 (58 mg, 0.051 mmol). Purify the crude product on silica gel (12 g) eluting with 50% to 70% THF/hexanes to afford two lots of yellow solid weighing 180 mg and 151 mg. Dissolve the 180 mg lot in boiling MeOH (20 mL), concentrate to 10 mL and cool to −26° C. to precipitate 165 mg (46%) of the title compound as a white solid. Repeat the recrystallization on the 151 mg lot to afford 98 mg (27%) of the title compound as a white solid. HPLC (ISO80-10) t=2.38 min, 97%; MS [ES] 375 (M−H), 377 (M+H); 1H-NMR (DMSO-d6) δ 10.57 (s, 1H), 10.46 (s, 1H), 7.57 (dd, 1H, J=8.4, 7.0 Hz), 7.49 (dd, 1H, J=9.2, 2.6 Hz), 7.08 (td, 1H, J=12.5, 4.3 Hz), 7.01 (d, 1H, J=5.7 Hz), 6.97 (s, 1H), 6.79 (td, 1H, J=12.0, 4.2 Hz), 6.73 (d, 1H, J=8.4 Hz), 6.67 (d, 1H, J=8.4 Hz), 6.61 (dd, 1H, J=10.6, 2.6 Hz), 6.52 (s, 1H), 5.78-4.78 (br d, 2H).
