Trifluoroacetic acid → HCID 178510346, compound

Participants

Reaction Conditions

Reaction Steps

In a 1 dram vial was added 6-chloro-8-((4-methoxybenzyl)(phenyl)amino)imidazo[1,2-b]pyridazine-7-carbonitrile (0.019 g, 0.049 mmol) from (1e), (trans)-cyclohexane-1,4-diamine (0.011 g, 0.097 mmol), cesium carbonate (0.048 g, 0.146 mmol), Pd(OAc)2 (0.547 mg, 2.437 μmol), (R)-(−)-1-[(S)-2-(dicyclohexylphosphino)ferrocenyl]ethyldi-tert-butylphospine [JOSI-Phos] (1.351 mg, 2.437 μmol) and the solids were pump/purged with argon (3×). Dioxane (1.0 ml, 0.05 M) was added and the reaction was heated at 100° C. overnight. Upon cooling, the mixture was filtered through a frit and the resulting solution was concentrated to dryness. To this residue was added TFA (1.0 ml) and the solution was stirred for 18 hours, concentrated and purified by HPLC to provide the titled compound (0.0031 g, 18% yield) as a TFA salt. 1H NMR (500 MHz, MeOH) δ ppm 7.78 (1H, s), 7.57 (1H, s), 7.43-7.51 (2H, m), 7.31-7.40 (3H, m), 3.77-3.89 (1H, m), 3.06-3.20 (1H, m), 2.18-2.29 (2H, m), 2.09 (2H, m), 1.36-1.62 (4H, m). LC/MS, m/z 348 (M+1). HPLC Rt, 1.78 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.

Provenance & Evidence