Reaction Steps
A solution of 1,1′-carbonyldiimidazole (79.6 mg, 0.491 mmol), 2-aminothiazole (48.2 mg, 0.481 mmol), and DIPEA (0.17 mL, 0.97 mmol) in CH2Cl2 (5 mL) and DMF (2 mL) was stirred at room temperature for 4 h. The mixture was concentrated to a minimum volume, diluted with DMF (3 mL), and COMPOUND 249 (150 mg, 0.482 mmol) was added and stirred at 60° C. for 20 hours. The solution was concentrated to dryness, treated with saturated aqueous NaHCO3 (30 mL) and H2O (10 mL), and extracted with CH2Cl2 (3×10 mL). The combined organic extracts were dried (Na2SO4), filtered, and concentrated. Purification of the crude material by flash chromatography on silica gel (CH2Cl2/MeOH/NH4OH, 90:5:5) followed by radial chromatography on a 1 mm TLC grade silica gel plate (CH2Cl2/MeOH/NH4OH, 96:2:2) provided COMPOUND 289 (27 mg, 13%) as a white solid. 1H NMR (CDCl3) δ 1.57-1.82 (m, 4H), 1.97 (d, 2H, J=11.7 Hz), 2.08 (s, 6H), 2.64-2.84 (m, 3H), 3.81 (s, 4H), 4.20 (d, 2H, J=12.9 Hz), 6.85 (d, 1H, J=3.6 Hz), 7.09 (dd, 2H, J=7.2, 5.1 Hz), 7.31 (d, 1H, J=3.6 Hz), 7.37 (d, 2H, J=7.5 Hz), 8.34 (d, 2H, J=4.5 Hz), 9.47 (br s, 1H); 13C NMR (CDCl3) 18.37, 27.47, 44.83, 54.97, 57.59, 113.16, 122.87, 133.78, 137.00, 138.47, 146.35, 153.46, 157.43, 161.07; ES-MS m/z 459 (M+Na). Anal. Calcd. for C23H28N6OS.0.3H2O.0.2 CH2Cl2: C, 60.71; H, 6.37; N, 18.31. Found: C, 61.05; H, 6.61; N, 17.94.
