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

Participants

Reaction Steps

A mixture of Example C2 (0.42 g, 1.02 mmol), N,N-dimethyl-3-azetidinamine dihydrochloride (0.176 g, 1.02 mmol) and N-methylpyrrolidine (0.182 g, 2.13 mmol) in dioxane (5 mL) was heated at 80° C. overnight, cooled to RT, concentrated to dryness and purified via silica gel chromatography (MeOH/DCM). The resultant material was dissolved in MeCN/H2O, frozen and lyophilized to afford 3-(dimethylamino)-N-(4-((6-(3-pivaloylureido)pyridin-3-yl)oxy)pyridin-2-yl)azetidine-1-carboxamide as a yellowish-white solid (59 mg, 11%). 1H NMR (400 MHz, DMSO-d6): δ 11.22 (s, 1H), 10.45 (s, 1H), 9.51 (s, 1H), 8.23 (d, J=2.9 Hz, 1H), 8.13 (d, J=5.7 Hz, 1H), 8.08 (d, J=9.0 Hz, 1H), 7.72 (dd, J=9.0, 2.9 Hz, 1H), 7.46 (d, J=2.38 Hz, 1H), 6.63 (dd, J=5.7, 2.4 Hz, 1H), 4.17-4.03 (m, 4H), 3.95-3.82 (br s, 1H), 2.62 (s, 6H), 1.21 (s, 9H); MS (ESI) m/z: 456.2 (M+H+).

Provenance & Evidence