Reaction Steps
A solution of 2-(1-ethyl-1H-pyrazol-4-yl)-8-(((3S,4S)-4-(fluoromethyl)pyrrolidin-3-yl)amino)imidazo[1,2-b]pyridazine-7-carboxamide, TFA (15 mg, 0.031 mmol), 1-cyanocyclopropanecarboxylic acid (6.85 mg, 0.062 mmol), HATU (17.59 mg, 0.046 mmol) and DIPEA (0.027 ml, 0.154 mmol) in DMF (0.4 ml) in a reaction vial was stirred at room temperature for 135 min. The crude material was purified via preparative LC/MS (Method A). Fractions containing the desired product were combined and dried via centrifugal evaporation to afford the title compound of Example 56 (8.5 mg, 59.2% yield). 1H NMR (500 MHz, DMSO-d6, two rotamers) δ 10.74 (d, J=8.9 Hz, 1H), 10.70 (d, J=8.4 Hz, 1H), 8.49 (br. s., 1H), 8.47 (br. s., 1H), 8.29 (br. s., 1H), 8.28 (br. s., 1H), 8.17 (s, 2H), 8.02 (br. s., 2H), 7.90 (s, 2H), 7.43 (br. s., 2H), 6.14 (br. s., 1H), 6.06 (br. s., 1H), 4.75 (d, J=5.4 Hz, 1H), 4.69 (d, J=6.4 Hz, 2H), 4.59 (d, J=6.9 Hz, 2H), 4.29 (dd, J=9.9, 5.9 Hz, 1H), 4.17 (q, J=7.4 Hz, 4H), 3.91-3.80 (m, 3H), 3.76 (dd, J=12.4, 8.9 Hz, 1H), 3.55 (d, J=10.9 Hz, 1H), 3.47 (dd, J=12.4, 7.4 Hz, 1H), 3.15 (dd, J=13.1, 6.2 Hz, 1H), 3.10-2.99 (m, 1H), 1.63 (br. s., 2H), 1.60-1.49 (m, 6H), 1.40 (t, J=7.2 Hz, 6H). HPLC/LCMS (Method F): m/z 466.21 ([M+H]+), Rt. 1.118 min.
