Potassium Carbonate → 1-methyl-N-(4-((6-(3-pivaloylureido)pyridin-3-yl)oxy)pyridin-2-yl)pyrrolidine-3-carboxamide

Participants

Reaction Steps

A solution of 1-methyl-pyrrolidine-3-carboxylic acid (0.082 g, 0.638 mmol) in thionyl chloride (3 mL, 41.1 mmol) and DCM (3 mL) was stirred at RT for 3 h, concentrated to dryness, suspended in THF (5 mL), added to a 0° C. solution of Example C1 (0.15 g, 0.455 mmol) and DIEA (0.239 mL, 1.366 mmol) in THF (5 mL), allowed to warm to RT and stirred overnight. The mixture was treated with 10% K2CO3, extracted with DCM (4×) and the combined organics were washed with brine, dried over Na2SO4, concentrated to dryness and purified via preparative TLC (MeOH/DCM/TEA) to afford 1-methyl-N-(4-((6-(3-pivaloylureido)pyridin-3-yl)oxy)pyridin-2-yl)pyrrolidine-3-carboxamide (113 mg, 56%). 1H NMR (400 MHz, DMSO-d6): δ 11.23 (s, 1H), 10.54 (s, 1H), 10.44 (s, 1H), 8.25 (d, J=2.9 Hz, 1H), 8.19 (d, J=5.7 Hz, 1H), 8.09 (d, J=9.0 Hz, 1H), 7.74 (dd, J=9.0, 2.9 Hz, 1H), 7.64 (d, J=2.4 Hz, 1H), 6.72 (dd, J=5.7, 2.4 Hz, 1H), 3.11 (m, 1H), 2.71 (t, J=8.5 Hz, 1H), 2.45-2.32 (m, 3H), 2.21 (s, 3H), 1.96-1.84 (m, 2H), 1.21 (s, 9H); MS (ESI) m/z: 441.2 (M+H+).

Provenance & Evidence