Reaction Steps
Benzoic acid 29 (150 mg, 0.34 mmol) was dissolved in anhydrous DMF (5 mL), DIEA (0.12 mL, 0.69 mmol) and HBTU (171 mg, 0.45 mmol) were successively added and the reaction mixture was stirred at 20° C. for 10 min. Benzylamine (0.16 mL, 1.4 mmol) was added and the reaction mixture was stirred at 20° C. for 1 h. The mixture was diluted with EtOAc (150 mL), washed with H2O (3×50 mL), washed with brine (50 mL) and dried. The solvent evaporated and the residue was purified by column chromatography, eluting with a gradient (50-100%) of EtOAc/pet. ether followed by a gradient (1-4%) MeOH/DCM, to afford amide 57 (117 mg, 66%) as a white solid: mp (DCM/MeOH) 234-237° C.; 1H NMR δ (t, J=5.9Hz, 1H, CONH), 8.01 (br d, J=8.6Hz, 2 H, H-2, H-6), 7.87 (br d, J=8.7Hz, 2 H, H-3, H-5), 7.85 (dt, J=8.8, 2.1Hz, 2 H, H-2′, H-6′), 7.72 (dt, J=8.7, 2.1Hz, 2 H, H-3′, H-5′), 7.34 (s, 2 H, H-2″, H-6″), 7.33 (s, 2 H, H-3″, H-5″), 7.22-7.28 (m, 1 H, H-4″), 4.74 (s, 2 H, CH2SO2), 4.49 (d, J=5.9Hz, 2 H, CH2NH), 2.21 (s, 3 H, CH3); 13C NMR δ 165.3, 158.0, 150.0, 139.4, 137.7, 135.6, 132.2 (2), 130.3 (2), 128.6, 128.2 (2), 128.1, 128.0 (2), 127.2 (2), 126.7, 125.6, 125.3 (2), 52.6, 42.6, 9.7; MS m/z 526.5, 528.5 (MH+, 100%). Anal. calcd for C25H21BrN2O4S: C, 57.15; H, 4.03; N, 5.33. Found: C, 57.34; H, 3.74; N, 5.50%.
