Example 31
To a solution of 6-amino-4-((2-methoxy-3-(2-methyl-2H-1,2,3-triazol-4-yl)phenyl)amino)-N-(methyl-d3)pyridazine-3-carboxamide (30 mg, 0.084 mmol), and 1-Propanephosphonic anhydride, in 50% DMF solution (160 mg, 0.252 mmol) in DMF (1 mL) and TEA (0.059 mL, 0.420 mmol) was added to 2,2-difluorocyclopropane-1-carboxylic acid (15.37 mg, 0.126 mmol) and the resulting mixture was stirred at 50° C. for 1 h., whereupon LC-MS indicated the reaction was complete. The mixture was diluted to 2 mL with DMF, filtered and purified by prep HPLC. Concentration of the pure fractions afforded 6-(2,2-difluorocyclopropane-1-carboxamido)-4-((2-methoxy-3-(2-methyl-2H-1,2,3-triazol-4-yl)phenyl)amino)-N-(methyl-d3)pyridazine-3-carboxamide (10.3 mg, 0.022 mmol, 26.3% yield). MS (M+1) m/z: 462.4 (M+H)+. LC retention time 1.28 [C] 1H NMR (500 MHz, DMSO-d6) δ 11.53 (s, 1H), 11.02 (s, 1H), 9.17 (s, 1H), 8.12 (s, 1H), 8.09 (s, 1H), 7.72 (d, J=7.6 Hz, 1H), 7.48 (d, J=7.9 Hz, 1H), 7.32 (t, J=7.9 Hz, 1H), 4.24 (s, 3H), 3.66 (s, 3H), 3.07-2.99 (m, 1H), 2.07-1.97 (m, 2H).
