Pyridine → US9133183, Example 1

Participants

Reaction Conditions

Reaction Steps

A 0° C. solution of Example A2 (6.4 g, 23.94 mmol) and pyridine (6 mL, 74.2 mmol) in DCM (150 mL) was treated with a solution of Example B2 (8.36 g, 35.9 mmol) in DCM (10 mL), stirred at 0° C. for 5 min, warmed to RT and stirred for 1.5 h. The mixture was diluted with water, stirred for 15 min, and the layers separated. The organic layer was washed with water and the combined aqueous layers were extracted with DCM (4×). The combined organics were dried over Na2SO4, concentrated to dryness, treated with MeOH and concentrated again to dryness. The residue was dissolved in DCM, sonicated, treated with MTBE, sonicated and the resulting solid collected via filtration. The solid was treated with Et2O, sonicated and again collected via filtration to afford N-(5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxo-3-(tetrahydro-2H-pyran-4-yl)imidazolidine-1-carboxamide (8.93 g, 80%). 1H NMR (400 MHz, DMSO-d6): δ 10.96 (s, 1 H), 8.36 (d, J=5.7 Hz, 1 H), 8.25 (s, 1 H), 8.23 (d, J=2.9 Hz, 1 H), 8.07 (dd, J=9.0, 0.7 Hz, 1 H), 7.96 (d, J=0.7 Hz, 1 H), 7.72 (dd, J=9.0, 2.9 Hz, 1 H), 7.22 (d, J=2.4 Hz, 1 H), 6.69 (dd, J=5.7, 2.5 Hz, 1 H), 3.93-3.87 (m, 3 H), 3.84 (s, 3 H), 3.83-3.77 (m, 2 H), 3.49-3.43 (m, 2 H) 3.42-3.34 (m, 2 H), 1.78-1.64 (m, 2 H), 1.59 (m, 2 H); MS (ESI) m/z: 464.2 (M+H+).

Provenance & Evidence