p-Toluenesulfonic acid → ethyl 6-((6-bromo-1H-benzo[d][1,2,3]triazol-1-yl)methyl)imidazo[1,2-b]pyridazine-2-carboxylate

Participants

Reaction Conditions

Reaction Steps

A mixture of 6-((6-bromo-1H-benzo[d][1,2,3]triazol-1-yl)methyl)pyridazin-3-amine 10G (4.8 g, 15.73 mmol), ethyl 3-bromo-2-oxopropanoate (4.60 g, 23.60 mmol) and NaHCO3 (4.0 g) in dioxane was heated at 60° C. for 1 hr. Additional ethyl 3-bromo-2-oxopropanoate (1.5 g, 7.87 mmol, 0.5 eq) was added and stirred at 60° C. for an additional hour. The reaction mixture was filtered and rinsed with dioxane. 4-Methylbenzenesulfonic acid (2.71 g, 15.73 mmol) was added to the filtrate, and the reaction was heated at 75° C. for 2 hrs. The reaction was evaporated to dryness via rotary evaporation and the resulting residue was dissolved in EtOAc. The organic phase was washed with saturated NaHCO3 followed by 0.1 N NaOH (3×150 mL). The solution was dried with MgSO4, filtered, concentrated to dryness and purified by MPLC (10% MeOH/CH2Cl2) to provide the title compound, ethyl 6-((6-bromo-1H-benzo[d][1,2,3]triazol-1-yl)methyl)imidazo[1,2-b]pyridazine-2-carboxylate 13A (4.7 g, 11.6 mmol, 50%). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.30 (t, J=7.07 Hz, 3 H) 4.30 (q, J=7.07 Hz, 2 H) 6.26 (s, 2 H) 7.33 (d, J=9.60 Hz, 1 H) 7.59 (dd, J=8.72, 1.64 Hz, 1H) 8.08 (d, J=8.84 Hz, 1 H) 8.23 (d, J=9.60 Hz, 1 H) 8.31 (d, J=1.26 Hz, 1 H) 8.77 (s, 1 H). MS:m/z 401.2 (M+H)+.

Provenance & Evidence