Reaction Steps
A solution of phosgene (15% in toluene, 1.440 g, 2.184 mmol) under Ar, was treated with a solution of Example B1 (0.149 g, 0.874 mmol) and pyridine (0.104 g, 1.310 mmol) in DCM (4 mL), stirred for 15 min, then concentrated to dryness. The residue was treated with a solution of Example A9 (0.129 g, 0.437 mmol) and TEA (0.221 g, 2.184 mmol) in DCM (4 mL), stirred for 0.5 h, then treated with water and EtOAc. The layers were separated, the aqueous layer extracted with additional EtOAc (1×) and the combined organics were washed with brine, dried over Na2SO4, concentrated to dryness and purified via reverse-phase chromatography (MeCN/H2O with 0.1% TFA). The organics were removed under reduced pressure and the aqueous residue was neutralized with satd. NaHCO3 and extracted with EtOAc (2×). The combined organics were washed with brine, dried over Na2SO4 and concentrated to dryness to afford N-(6-ethyl-5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxo-3-(tetrahydro-2H-pyran-4-yl)imidazolidine-1-carboxamide (130 mg, 60%). 1H NMR (400 MHz, DMSO-d6): δ 10.91 (s, 1 H), 8.33 (d, J=5.7 Hz, 1 H), 8.24 (s, 1 H), 7.94 (d, J=0.7 Hz, 1 H), 7.89 (d, J=8.8 Hz, 1 H), 7.59 (d, J=8.8 Hz, 1 H), 7.17 (d, J=2.4 Hz, 1 H), 6.58 (dd, J=5.7, 2.4 Hz, 1 H), 3.90-3.87 (m, 3 H), 3.83 (s, 3 H), 3.81-3.79 (m, 2 H), 3.45 (t, J=8.3 Hz, 2 H), 3.37 (dd, J=12.4, 10.5 Hz, 2 H), 2.56 (q, J=7.5 Hz, 2 H), 1.71 (qd, J=12.2, 4.5 Hz, 2 H), 1.62-1.58 (m, 2 H), 1.10 (t, J=7.5 Hz, 3H); MS (ESI) m/z: 492.3 (M+H+).
