反应详情

To a 2 dram vial was added crude N6-((trans)-4-aminocyclohexyl)-N8-(4-methoxybenzyl)-N8-phenyl-3-(prop-1-ynyl)imidazo[1,2-b]pyridazine-6,8-diamine (0.065 g, 0.13 mmol) from (1b) and a 1:1 mixture of TFA and CH2Cl2 (2 ml). The reaction was stirred for 2 hours, concentrated, diluted with MeOH and purified by preparative HPLC to provide the titled compound (0.0025 g, 5%) as a TFA salt. 1H NMR (400 MHz, MeOD) δ ppm 7.44 (2H, dd, 8 Hz), 7.33 (2H, d, 8 Hz), 7.18-7.26 (1H, m), 7.18-7.25 (2H, m), 6.39 (1H, s), 3.68-3.82 (1H, m), 3.06-3.21 (1H, m), 2.23-2.35 (2H, m), 2.18 (3H, s), 1.46-1.62 (2H, m), 1.25-1.41 (2H, m). LC/MS, m/z 361 (M+1). HPLC Rt, 2.30 min. Waters Sunfire C18 column (4.6×50 mm). 0%-100% B. Solvent B: (90% MeOH, 10% H2O, 0.1% TFA). Solvent A: (10% MeOH, 90% H2O, 0.1% TFA). Gradient, start % B=0, final % B=100, gradient time 4 min, hold at 100% B 1 min, flow rate 4 mL/min.

1. concentrationconcentrated
2. additiondiluted with MeOH
3. custompurified by preparative HPLC