Trifluoroacetic acid → N6-(4-Aminocyclohexyl)-N8-phenyl-3-((E)-2-(4-pyridinyl)vinyl)imidazo[1,2-b]pyridazine-6,8-diamine
Reaction equation
[NH2:1][C@H:2]1[CH2:7][CH2:6][C@H:5]([NH:8][C:9]2[CH:10]=[C:11]([N:26](CC3C=CC(OC)=CC=3)[C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)[C:12]3[N:13]([C:15]([CH:18]=[CH:19][C:20]4[CH:25]=[CH:24][N:23]=[CH:22][CH:21]=4)=[CH:16][N:17]=3)[N:14]=2)[CH2:4][CH2:3]1.C(O)(C(F)(F)F)=O>ClCCl>[NH2:1][CH:2]1[CH2:3][CH2:4][CH:5]([NH:8][C:9]2[CH:10]=[C:11]([NH:26][C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)[C:12]3[N:13]([C:15](/[CH:18]=[CH:19]/[C:20]4[CH:25]=[CH:24][N:23]=[CH:22][CH:21]=4)=[CH:16][N:17]=3)[N:14]=2)[CH2:6][CH2:7]1Participants
4
Procedure
To N6-(trans-4-aminocyclohexyl)-N8-(4-methoxybenzyl)-N8-phenyl-3-(2-(pyridin-4-yl)vinyl)imidazo[1,2-b]pyridazine-6,8-diamine (30 mg) from step (1c) in dichloromethane at room temperature was added excess TFA. The mixture was stirred for 30 min, concentrated, and the resulting residue was purified by reverse phase preparative HPLC to provide the titled compound as a yellow solid (21 mg). NMR (400 MHz, DMSO-d6) δ ppm 9.05 (1H, s), 8.66 (2H, m), 7.78-7.90 (8H, m), 7.39-7.44 (4H, m), 7.16 (1H, m), 6.68 (1H, m), 6.26 (1H, s), 3.62 (1H, m), 3.08 (1H, m), 2.20 (2H, m), 2.02 (2H, m), 1.51-1.54 (2H, m), 1.25-1.29 (2H, m). LC/MS, m/e 426 (M+1). HPLC Rt, 1.89 min. YMC S5 ODSC18 column (4.6×50 mm). 0%-100% B. Solvent B: (90% MeOH, 10% H2O, 0.2% H3PO4)—Solvent A: (10% MeOH, 90% H2O, 0.2% H3PO4). Gradient, start % B=0, final % B=100, gradient time 4 min, hold at 100% B 1 min, flow rate 4 mL/min.