Example 85
To crude (1s,4s)-4-(6-cyclopropoxy-5-iodo-2H-indazol-2-yl)cyclohexan-1-ol (Int IV-1) (70 mg, 0.2 mmol), dppp (7 mg, 0.02 mmol), TEA (98 μL, 0.7 mmol), and imidazo[1,2-b]pyridazin-3-amine (54 mg, 0.4 mmol) in MeCN (5 mL) was added Pd(OAc)2 (5 mg, 0.02 mmol) and the resulting mixture was stirred under a 15 atm CO atmosphere at 90° C. After 12 h the reaction mixture was allowed to cool to rt and the solvent was removed in vacuo. The resulting residue was purified using C18-flash chromatography (eluting with 0% to 100% MeCN in water (0.1% FA)) to afford 6-cyclopropoxy-2-((1s,4s)-4-hydroxycyclohexyl)-N-(imidazo[1,2-b]pyridazin-3-yl)-2H-indazole-5-carboxamide (7 mg, 9%) as a pale-yellow solid. 1H NMR (300 MHz, DMSO-d6) δ 10.94 (s, 1H), 8.65 (dd, 1H), 8.63 (s, 1H), 8.62 (s, 1H), 8.15 (dd, 1H), 8.07 (s, 1H), 7.55 (s, 1H), 7.22 (dd, 1H), 4.43-4.59 (m, 2H), 4.20-4.29 (m, 1H), 3.86-3.93 (m, 1H), 2.22-2.39 (m, 2H), 1.72-1.95 (m, 4H), 1.57-1.72 (m, 2H), 1.07-1.15 (m, 2H), 0.97-1.07 (m, 2H). m/z (ESI+), [M+H]+=433.
