1-Methylpyrrolidine → HCID 86275386, compound

Participants

Reaction Steps

A mixture of Example C2 (0.120 g, 0.29 mmol), 1-methyl-4-(piperidin-4-yl)piperazine (0.053 g, 0.290 mmol) and N-methylpyrrolidine (0.012 g, 0.15 mmol) in dioxane (5 mL) was heated at 80° C. for 2 days. The reaction mixture was concentrated to dryness. The residue was dissolved in DCM and stirred with sat'd NaHCO3. The aqueous layer was back-extracted with DCM (3×) and the organic phases combined, dried (Na2SO4) and concentrated to afford a light brown oil. The crude residue was purified via silica gel chromatography (MeOH/DCM/Et3N) to afford a light yellow oil, which was dissolved in MeCN/H2O, frozen and lypholized overnight to afford 4-(4-methylpiperazin-1-yl)-N-(4-((6-(3-pivaloylureido)pyridin-3-yl)oxy)pyridin-2-yl)piperidine-1-carboxamide as a white solid (63 mg, 40%). 1H NMR (400 MHz, DMSO-d6): δ 11.22 (s, 1H), 10.44 (s, 1H), 9.22 (s, 1H), 8.23 (d, J=2.9 Hz, 1H), 8.12-8.05 (m, 2H), 7.71 (dd, J=9.0, 2.9 Hz, 1H), 7.36 (d, J=2.4 Hz, 1H), 6.59 (dd, J=5.7, 2.4 Hz, 1H), 4.13-4.02 (m, 2H), 3.38-3.31 (m, 1H), 2.77-2.64 (m, 2H), 2.52-2.26 (m, 8H), 2.16 (s, 3H), 1.75-1.62 (m, 2H), 1.31-1.23 (m, 2H), 1.21 (s, 9H); MS (ESI) m/z: 539.4 (M+H+).

Provenance & Evidence