反应详情

Phosgene (20% in toluene, 0.613 g, 1.24 mmol) was treated with a solution of Example B1 (0.063 g, 0.37 mmol) and pyridine (0.1 mL, 1.24 mmol) in DCM (2 mL), stirred for 15 min, then concentrated to dryness. The residue was dissolved in DCM (2 mL), treated with a solution of 6-methyl-5-((2-(3-methylisoxazol-5-yl)pyridin-4-yl)oxy)pyridin-2-amine (0.07 g, 0.25 mmol) and TEA (0.17 mL, 1.24 mmol) in DCM (2 mL) and stirred at RT for 1 h. The mixture was treated with satd. NaHCO3, extracted with EtOAc (2×) and the combined organics were washed with brine, dried over Na2SO4, concentrated to dryness and purified via silica gel chromatography (MeOH/DCM) to afford N-(6-methyl-5-((2-(3-methylisoxazol-5-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxo-3-(tetrahydro-2H-pyran-4-yl)imidazolidine-1-carboxamide (75 mg, 63%). 1H NMR (400 MHz, DMSO-d6): δ 10.92 (s, 1 H), 8.55 (d, J=5.7 Hz, 1 H), 7.92 (d, J=8.8 Hz, 1 H), 7.67 (d, J=8.8 Hz, 1 H), 7.34 (d, J=2.5 Hz, 1 H), 6.98 (s, 1 H), 6.96 (dd, J=5.7, 2.5 Hz, 1 H), 3.95-3.77 (m, 5 H), 3.48-3.35 (m, 4 H), 2.28 (s, 3 H), 2.24 (s, 3 H), 1.71-1.70 (m, 2 H), 1.60 (d, J=12.5 Hz, 2 H); MS (ESI) m/z: 479.2 (M+H+).

1. concentrationconcentrated to dryness
2. dissolutionThe residue was dissolved in DCM (2 mL)
3. stirringstirred at RT for 1 h
4. additionThe mixture was treated with satd
5. extractionNaHCO3, extracted with EtOAc (2×)
6. washthe combined organics were washed with brine
7. dry with materialdried over Na2SO4
8. concentrationconcentrated to dryness
9. custompurified via silica gel chromatography (MeOH/DCM)