Reaction Steps
To a solution of methyl 4-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-3-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzoate (2.0 g, 5.05 mmol) in dioxane (40 mL) was added Pd(dppf)2Cl2 (77 mg, 0.10 mmol), 2-bromo-N,N-dibutyl-1-((2-(trimethylsilyl) ethoxy)methyl)-1H-imidazole-4-carboxamide (910 mg, 2.10 mmol) and K3PO4 (1.34 g, 6.31 mmol). The reaction mixture was degassed for 30 min, heated at 100° C. for 16 h and concentrated in vacuo. The resulting residue was dissolved in EtOAc and washed with water, dried over Na2SO4, and concentrated to give the crude product. The crude material was purified by flash chromatography (gradient from 0% to 80%, EtOAc/hexanes) to provide the title compound (800 mg, 57%). 1H NMR (CD3OD, 1:1 mixture of amide rotamers) δ 8.23 (dd, J=6.4, 1.6 Hz, 1H), 8.13-8.12 (m, 1H), 7.98 (dd, J=14.4, 8.0 Hz, 1H), 7.78 (s, 0.5H), 7.67 (s, 0.5H), 7.24-7.12 (m, 3.5H), 6.93 (d, J=7.2 Hz, 0.5H), 5.39 (s, 1H), 5.30 (s, 1H), 4.85-4.75 (m, 2H), 4.58-4.35 (m, 1H), 3.99 (s, 3H), 3.71-3.62 (m, 3H), 3.56 (t, J=6.0 Hz, 2H), 3.45-3.36 (m, 2H), 2.90-2.80 (m, 2H), 1.65-1.31 (m, 8H), 1.00-0.91 (m, 5H), 0.80-0.73 (m, 3H), 0.04 (s, 4.5H), 0.02 (s, 4.5H); MS (ESI−) m/z 646.2 (M−H)−.
