Pyridine → N-(6-ethyl-5-((2'-methyl-[2,4'-bipyridin]-4-yl)oxy)pyridin-2-yl)-2-oxo-3-(tetrahydro-2H-pyran-4-yl)imidazolidine-1-carboxamide

Participants

Reaction Steps

A 0° C. solution of Example B1 (0.19 g, 1.116 mmol) and pyridine (0.26 mL, 3.21 mmol) in DCM (5 mL) was treated drop-wise with phosgene (20% in toluene, 1.4 mL, 2.65 mmol), warmed to RT over 0.5 h, then treated slowly with a solution of 6-ethyl-5-((2′-methyl-[2,4′-bipyridin]-4-yl)oxy)pyridin-2-amine (0.13 g, 0.424 mmol) and pyridine (0.16 mL, 1.978 mmol) in DCM (5 mL) and stirred at RT overnight. The mixture was treated with satd. NaHCO3, extracted with EtOAc (4×) and the combined organics were dried over MgSO4, concentrated to dryness, purified via silica gel chromatography (MeOH/DCM), then re-purified via reverse-phase chromatography (MeCN/H2O with 0.1% TFA). The organics were removed under reduced pressure, the aqueous residue treated with satd. NaHCO3, extracted with DCM (5×) and the combined organics were dried over MgSO4 and concentrated to dryness to afford N-(6-ethyl-5-((2′-methyl-[2,4′-bipyridin]-4-yl)oxy)pyridin-2-yl)-2-oxo-3-(tetrahydro-2H-pyran-4-yl)imidazolidine-1-carboxamide (8 mg, 4%). 1H NMR (400 MHz, DMSO-d6): δ 10.93 (s, 1 H), 8.56 (d, J=5.7 Hz, 1 H), 8.52 (d, J=5.3 Hz, 1 H), 7.93-7.89 (m, 2 H), 7.67 (d, J=2.4 Hz, 1 H), 7.68-7.66 (m, 1 H), 7.64 (s, 1 H), 6.86 (dd, J=5.7, 2.4 Hz, 1 H), 3.94-3.78 (m, 5 H), 3.49-3.34 (m, 4 H), 2.58 (q, J=7.5 Hz, 2 H), 2.53 (s, 3H), 1.78-1.66 (m, 2 H), 1.64-1.57 (m, 2 H), 1.12 (t, J=7.5 Hz, 3H); MS (ESI) m/z: 503.3 (M+H+).

Provenance & Evidence