Reaction Steps
To a solution of COMPOUND 249 (0.100 g, 0.322 nmol) in CH2Cl2 (5 mL) was added 1H-benzoimidazole-4-carbonyl chloride (0.118 g, 0.653 mmol) (White, A. W. et al. J. Med. Chem. 2000, 43, 4084-4097) and Et3N (0.37 g, 0.37 mmol). After the mixture was stirred overnight water (10 mL) was added, and the mixture was extracted with CH2Cl2 (3×20 mL). The extracts were combined and dried over anhydrous Na2SO4. After filtration the solvent was removed by evaporation under vacuum, and the residue was purified by flash chromatography on silica gel columns (column 1, 6:1 EtOAc/MeOH; column 2, 100:5:1 CH2Cl2/MeOH/NH4OH), affording a white solid (0.080 g, 56%). Conversion to the HBr salt using General Procedure D gave a white solid. 1H NMR (D2O) δ 1.55-1.84 (m, 2H), 1.95-1.99 (m, 1H), 2.18-2.22 (m, 1H), 2.45 (s, 6H), 2.88-3.20 (m, 3H), 3.72-3.77 (m, 1H), 4.32 (s, 4H), 4.63-4.70 (m, 1H), 7.61-7.67 (m, 2H), 7.74-7.80 (m, 2H), 7.89-7.93 (m, 1H), 8.28 (d, 2H, J=8.1 Hz), 8.50 (d, 2H, J=5.7 Hz), 9.20 (s, 1H); 13C NMR (D2O) δ 17.41, 27.50, 28.20, 42.48, 47.56, 51.01, 60.02, 117.02, 121.50, 125.51, 126.16, 127.09, 127.71, 131.38, 137.93, 138.77, 140.71, 148.67, 151.08, 167.43. ES-MS m/z 455 (M+Na). Anal. Calcd. for C27H30N6O.3.5HBr.0.25H2O.0.3C4H10O: C, 42.07; H, 5.20; N, 10.44; Br, 34.74. Found: C, 41.86; H, 5.18; N, 10.39; Br, 34.98.
