Reaction SMILES: [NH2:1][C@H:2]1[CH2:7][CH2:6][C@H:5]([NH:8][C:9]2[CH:10]=[C:11]([N:28]([CH:38]3[CH2:40][CH2:39]3)CC3C=CC(OC)=CC=3)[C:12]3[N:13]([C:15]([C:18]([NH:20][C:21]4[CH:26]=[CH:25][N:24]=[C:23]([F:27])[CH:22]=4)=[O:19])=[CH:16][N:17]=3)[N:14]=2)[CH2:4][CH2:3]1.[CH:41](=O)[CH3:42].C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(O)(C(F)(F)F)=O>C(Cl)Cl>[CH:38]1([NH:28][C:11]2[C:12]3[N:13]([C:15]([C:18]([NH:20][C:21]4[CH:26]=[CH:25][N:24]=[C:23]([F:27])[CH:22]=4)=[O:19])=[CH:16][N:17]=3)[N:14]=[C:9]([NH:8][C@H:5]3[CH2:6][CH2:7][C@H:2]([NH:1][CH2:41][CH3:42])[CH2:3][CH2:4]3)[CH:10]=2)[CH2:39][CH2:40]1
Reactant: CC=O
Reactant: COc1ccc(CN(c2cc(N[C@H]3CC[C@H](N)CC3)nn3c(C(=O)Nc4ccnc(F)c4)cnc23)C2CC2)cc1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Solvent: CC(=O)O
Product: CCN[C@H]1CC[C@H](Nc2cc(NC3CC3)c3ncc(C(=O)Nc4ccnc(F)c4)n3n2)CC1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
To a solution of 6-((trans)-4-aminocyclohexylamino)-8-(cyclopropyl(4-methoxybenzyl)amino)-N-(2-fluoropyridin-4-yl)imidazo[1,2-b]pyridazine-3-carboxamide (60.0 mg, 0.110 mmol), acetaldehyde (14.56 mg, 0.331 mmol) and acetic acid (13.23 mg, 0.220 mmol) in DCM (2 mL) was stirred at room temperature for 5 minutes, then sodium triacetoxyborohydride (46.7 mg, 0.220 mmol) was added and the reaction was stirred at 25° C. for 2 hrs. The reaction mixture was concentrated down and treated with TFA (0.509 mL, 6.61 mmol) at 65° C. for 1 hr, concentrated, diluted in methanol and purified by preparative HPLC (Phenomenex Axia Luna 5 micron 30×100 mm) 30% B (Solvent B=90% MeOH-10% H2O-0.1% TFA) to 100% B in A (Solvent A=10% MeOH-90% H2O-0.1% TFA) to isolate 8-(cyclopropylamino)-6-((trans)-4-(ethylamino)cyclohexylamino)-N-(2-fluoropyridin-4-yl)imidazo[1,2-b]pyridazine-3-carboxamide (19.3 mg, 0.043 mmol, 38.7% yield). LC/MS (BEH C18 2.1×50 mm 1.7u, Phenomenex Luna 5 micron C18 4.6×30 mm, 0 to 100 B in 2.2 min with 1 min hold time, Flow rate=2 mL/min, detection at 254 nm, Solvent A: 100% water/0.05% TFA; Solvent B: 100% ACN/0.05% TFA). Rt=0.67 minutes [M+H]=453.2. 1H NMR (400 MHz, DMSO-d6) δ ppm 11.52 (1H, s), 8.21 (1H, d, J=5.52 Hz), 7.96 (1H, s), 7.60 (1H, d, J=1.51 Hz), 7.51 (2H, s), 6.86-7.03 (1H, m), 5.98 (1H, s), 3.57-3.76 (1H, m), 2.56 (2H, d, J=7.03 Hz), 2.33-2.47 (1H, m), 2.02-2.20 (2H, m), 1.80-2.02 (2H, m), 1.18-1.37 (2H, m), 1.04-1.18 (2H, m), 1.01 (3H, t, J=7.03 Hz), 0.69-0.85 (2H, m), 0.53-0.71 (2H, m) and 8-(cyclopropylamino)-6-((trans)-4-(diethylamino)cyclohexylamino)-N-(2-fluoropyridin-4-yl)imidazo[1,2-b]pyridazine-3-carboxamide (25.6 mg, 0.053 mmol, 48.4% yield).). LC/MS (BEH C18 2.1×50 mm 1.7u, Phenomenex Luna 5 micron C18 4.6×30 mm, 0 to 100 B in 2.2 min with 1 min hold time, Flow rate=2 mL/min, detection at 254 nm, Solvent A: 100% water/0.05% TFA; Solvent B: 100% ACN/0.05% TFA). Rt=0.69 minutes [M+H]=481.3. 1H NMR (400 MHz, DMSO-d6) δ ppm 11.33-11.48 (1H, m), 8.29-8.48 (1H, m), 8.21 (1H, d, J=5.52 Hz), 7.98 (1H, s), 7.64 (1H, d, J=1.25 Hz), 7.53-7.63 (1H, m), 7.51 (1H, s), 6.97-7.11 (1H, m), 6.00 (1H, s), 3.62-3.81 (1H, m), 2.97-3.14 (1H, m), 2.92 (4H, q, J=7.28 Hz), 2.15-2.32 (2H, m), 1.95-2.09 (2H, m), 1.49-1.67 (2H, m), 1.27-1.46 (2H, m), 1.02-1.30 (6H, m), 0.71-0.85 (2H, m), 0.56-0.72 (2H, m)