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

Participants

Reaction Steps

A mixture of Example C2 (0.42 g, 1.02 mmol), 4-(dimethylamino)piperidine dihydrochloride (0.204 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 4-(dimethylamino)-N-(4-((6-(3-pivaloylureido)pyridin-3-yl)oxy)pyridin-2-yl)piperidine-1-carboxamide as a yellowish solid (64 mg, 13%). 1H NMR (400 MHz, DMSO-d6): δ 11.17 (s, 1H), 10.40 (s, 1H), 9.23 (s, 1H), 8.18 (d, J=2.9 Hz, 1H), 8.07 (d, J=5.7 Hz, 1H), 8.03 (d, J=9.0 Hz, 1H), 7.66 (dd, J=9.0, 2.9 Hz, 1H), 7.32 (d, J=2.4 Hz, 1H), 6.56 (dd, J=5.7, 2.4 Hz, 1H), 4.13-4.01 (m, 2H), 3.37-3.11 (br s, 1H), 2.74-2.62 (m, 2 H), 2.28 (s, 6H), 1.76-1.70 (m, 2H), 1.29-1.24 (m, 2H), 1.16 (s, 9H); MS (ESI) m/z: 484.3 (M+H+).

Provenance & Evidence