Ethyl Acetate → 3-(2-methoxyethyl)-N-(6-methyl-5-((2-(1-methyl-1H-imidazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxoimidazolidine-1-carboxamide

Participants

Reaction Conditions

Reaction Steps

A mixture of Example C5 (0.150 g, 0.370 mmol), N-methyl-4-(tributylstannyl)imidazole (0.178 g, 0.480 mmol) and Pd(PPh3)4 (0.021 g, 0.018 mmol) in toluene (4 mL) was sparged with Ar and heated at 105° C. overnight. The mixture was cooled to RT, treated with 10% KF and EtOAc, stirred for 2 h and the solids removed via filtration through diatomaceous earth. The filtrate was extracted with EtOAc (3×) and the combined organics were washed with 10% KF, then brine, dried over Na2SO4 and concentrated to dryness. The material was treated with MeCN, sonicated, the solid removed via filtration and the filtrate concentrated to dryness and purified via silica gel chromatography (MeOH/DCM). The material was suspended in MeCN, sonicated and the solid collected via filtration. The filtrate was concentrated to dryness and further 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 EtOAc (3×) and the combined organics were dried over Na2SO4, concentrated to dryness and combined with the above-isolated solid to afford 3-(2-methoxyethyl)-N-(6-methyl-5-((2-(1-methyl-1H-imidazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxoimidazolidine-1-carboxamide (61 mg, 36%). 1H NMR (400 MHz, DMSO-d6): δ 10.89 (s, 1 H), 8.35 (d, J=5.7 Hz, 1 H), 7.91 (d, J=8.8 Hz, 1H), 7.67 (d, J=1.3 Hz, 1 H), 7.64 (d, J=8.8 Hz, 1 H), 7.59 (d, J=1.3 Hz, 1 H), 7.16 (d, J=2.6 Hz, 1 H), 6.74 (dd, J=5.7, 2.6 Hz, 1 H), 3.84-3.78 (m, 2 H), 3.67 (s, 3 H), 3.54-3.47 (m, 4 H), 3.41-3.37 (m, 2 H), 3.26 (s, 3 H), 2.23 (s, 3H); MS (ESI) m/z: 452.2 (M+H+).

Provenance & Evidence