Reaction Steps
To a stirred solution of 49 (100 mg, 0.19 mmol) and triethylamine (107 μl, 0.77 mmol) in DCM (10 ml) under nitrogen was added chloroacetyl chloride (19 μl, 0.23 mmol), and the reaction mixture was stirred at rt for 25 min. N,N-Dimethylethylene diamine (134 μl, 1.16 mmol) was added, and the reaction mixture was stirred at rt overnight, heated at 40° C. for 5 h, then at rt. The reaction mixture was concentrated, diluted with water and few drops of 1N NaOH and sonicated. The resulting gel was collected by filtration, rinsed with water and air-dried. The crude product was purified three times by Biotage [Snap 30 g cartridge KP-C18-HS (reverse phase) ×2: MeOH/water (Millipore): 20/80 to 95/05 over 40 CV; Analogix SF 25-40 g cartridge; 2% of ammonium hydroxide in MeOH/DCM: 1/99 to 50/50 over 60 CV], to afford the desired compound 549 (13 mg, 0.02 mmol, 10% yield) as a pale yellow sticky solid. 1H NMR (500 MHz, DMSO-d6) δ (ppm): 8.75 (s, 1H), 8.56 (bd, J=1.7 Hz, 1H), 8.51 (d, J=5.4 Hz, 1H), 8.32 (s, 1H), 8.24 (d, J=8.1 Hz, 1H), 7.87 (dd, J=8.2, 1.9 Hz, 1H), 7.72 (dd, J=13.6, 2.4 Hz, 1H), 7.37 (t, J=9.1 Hz, 1H), 7.20 (bd, J=8.9 Hz, 1H), 6.64 (d, J=5.4 Hz, 1H), 6.61 (bd, J=1.9 Hz, 1H), 3.58 (s, 2H), 3.50-3.36 (m, 4H), 3.33 (s, 2H), 2.59-2.51 (m, 1H), 2.52 (t, J=6.3 Hz, 2H), 2.43-2.31 (m, 4H), 2.27 (t, J=6.3 Hz, 2H), 2.10 (s, 6H), 0.70-0.58 (m, 2H), 0.47-0.37 (m, 2H), one NH secondary amine is missing. MS (m/z): 647.6 (M+H).
