1-Methylpyrrolidine → N-(4-((6-(3-pivaloylureido)pyridin-3-yl)oxy)pyridin-2-yl)azetidine-1-carboxamide

Participants

Reaction Steps

A mixture of Example C2 (0.265 g, 0.641 mmol), azetidine hydrochloride (0.120 g, 1.282 mmol) and N-methylpyrrolidine (0.065 g, 0.769 mmol) in dioxane (6 mL) was heated at 80° C. overnight, cooled to RT, concentrated to dryness and purified 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, extracted with EtOAc (4×) and the combined organics were dried over Na2SO4 and concentrated to dryness to afford N-(4-((6-(3-pivaloylureido)pyridin-3-yl)oxy)pyridin-2-yl)azetidine-1-carboxamide (70 mg, 25%). 1H NMR (400 MHz, DMSO-d6): δ 11.21 (s, 1H), 10.43 (s, 1H), 9.09 (s, 1H), 8.23 (d, J=2.9 Hz, 1H), 8.11-8.06 (m, 2H), 7.71 (dd, J=9.0, 2.9 Hz, 1H), 7.48 (d, J=2.4 Hz, 1H), 6.59 (dd, J=5.7, 2.4 Hz, 1H), 3.92 (t, J=7.5 Hz, 4H), 2.12-2.10 (m, 2H), 1.21 (s, 9H); MS (ESI) m/z: 413.2 (M+H+).

Provenance & Evidence