Potassium Phosphate, Tribasic → HCID 86270035, compound

Participants

Reaction Steps

A solution of Pd2(dba)3 (0.029 g, 0.032 mmol) and Me4t-BuXPhos (0.034 g, 0.072 mmol) in toluene (0.6 mL) and dioxane (1.2 mL) was heated at 120° C. for 3 min, cooled to RT, added to a degassed suspension of N-(5-((2-chloropyridin-4-yl)oxy)-4-methylpyridin-2-yl)-3-ethyl-2-oxoimidazolidine-1-carboxamide (0.3 g, 0.798 mmol), 4-methyl imidazole (0.085 g, 1.038 mmol) and K3PO4 (0.339 g, 1.597 mmol) in toluene (1.2 mL) and dioxane (2.4 mL) and heated at 110° C. overnight. The mixture was treated with additional catalyst (synthesized from Pd2(dba)3 (0.029 g, 0.032 mmol) and Me4t-BuXPhos (0.034 g, 0.072 mmol) in toluene (0.6 mL) and dioxane (1.2 mL) as above) and heated at 110° C. overnight. The mixture was cooled to RT, treated with satd. NaHCO3, extracted with EtOAc (5×) and the combined organics were dried over Na2SO4, concentrated to dryness and purified twice via silica gel chromatography (MeOH/DCM). The material was further purified via reverse-phase chromatography (MeCN/H2O with 0.1% TFA); the organics were removed under reduced pressure and the aqueous residue was treated with satd. NaHCO3 and extracted with DCM (3×). The combined organics were dried over Na2SO4 and concentrated to dryness to afford 3-ethyl-N-(4-methyl-5-((2-(4-methyl-1H-imidazol-1-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxoimidazolidine-1-carboxamide (112 mg, 32%). 1H NMR (400 MHz, DMSO-d6): δ 10.93 (s, 1 H), 8.39 (d, J=1.4 Hz, 1 H), 8.30 (d, J=5.8 Hz, 1 H), 8.13 (s, 1 H), 8.02 (s, 1 H), 7.64 (s, 1 H), 7.33 (d, J=2.2 Hz, 1 H), 6.73 (dd, J=5.8, 2.2 Hz, 1 H), 3.80 (t, J=8.3 Hz, 2H), 3.46 (t, J=8.2 Hz, 2 H), 3.26-3.25 (q, J=7.2 Hz, 2 H), 2.15 (s, 3 H), 2.13 (s, 3 H), 1.09 (t, J=7.2 Hz, 3H); MS (ESI) m/z: 422.2 (M+H+).

Provenance & Evidence