tert-Butyl 5-bromo-3,4-dihydroisoquinoline-2(1H)-carboxylate (0.20 g, 0.64 mmol), 4-(methoxycarbonylamino)phenylboronic acid (0.125 g, 0.641 mmol), potassium phosphate tribasic (0.476 g, 2.24 mmol) and tricyclohexylphosphine (0.018 g, 0.064 mmol) were placed in a pressure vial containing toluene (10 mL) and H2O (1.0 mL) which had been degassed with argon for 15 minutes. Pd(OAc)2 (7.19 mg, 0.032 mmol) was added, the vial was sealed, and heated at 100° C. for 12 h. After cooling to rt, the reaction mixture was diluted with EtOAc (50 mL), and filtered through a plug of celite. The filtrate was washed with H2O (50 mL). The aqueous phase was extracted with EtOAc (3×25 mL). Combined organic extract was washed with brine, dried (Na2SO4), filtered, and concentrated. Purification by silica gel chromatography gave tert-butyl 5-(4-(methoxycarbonylamino)phenyl)-3,4-dihydroisoquinoline-2(1H)-carboxylate as a colorless oil (75 mg, 31%). This material was treated with 50% TFA/DCM for 48 h and then concentrated. The resulting oil was dissolved in EtOAc and neutralized with saturated NaHCO3. The organic layer was washed with H2O, brine, dried over Na2SO4, filtered, and concentrated. The residue was oxidized as in Example 8B and then carried onto an Ugi reaction with Intermediate 2 and Intermediate 6 in a similar manner as Example 8 followed by TFA deprotection. Purification by reverse phase HPLC and freeze-drying afforded Example 39 (8 mg, 1.75%) as a white solid. 1H NMR (500 MHz, DMSO-d6) δ 12.70 (1H, br.s.), 10.81 (1H, s), 9.86 (1H, s), 9.76 (1H, s), 8.38 (1H, d, J=2.21 Hz), 7.88 (2H, d, J=8.83 Hz), 7.68-7.79 (4H, m), 7.63 (1H, d, J=7.57 Hz), 7.49-7.58 (3H, m), 7.33 (1H, t, J=7.72 Hz), 7.26-7.31 (2H, m), 7.22 (1H, d, J=7.57 Hz), 6.96 (1H, d, J=15.45 Hz), 5.88 (1H, s), 4.22-4.30 (1H, m), 3.72-3.80 (1H, m), 3.03-3.12 (1H, m), 2.86-2.94 (1H, m) ppm. MS (ESI) m/z: 678.0 (M+H)+. Analytical HPLC: RT=6.76 min.
