反应详情

温度

80 °C

A suspension of 2,2,2-trimethylacetamide (0.149 g, 1.469 mmol) in DCE (4 mL) was treated with oxalyl chloride (0.129 mL, 1.469 mmol), heated at 80° C. for 1 h, cooled to RT, added drop-wise to a solution of 4-((6-aminopyridin-3-yl)oxy)-N-isopropylpicolinamide (0.2 g, 0.734 mmol) and DIEA (0.641 mL, 3.67 mmol) in dioxane (4 mL) and stirred at RT overnight. The mixture was diluted with EtOAc, washed with satd. NaHCO3, water, and brine, and the combined aqueous washes were back-extracted with EtOAc. The combined organics were dried over Na2SO4, concentrated to dryness and purified by silica gel chromatography (EtOAc/DCM) to afford N-isopropyl-4-((6-(3-pivaloylureido)pyridin-3-yl)oxy)picolinamide (0.241 g, 82%). 1H NMR (400 MHz, DMSO-d6): δ 11.24 (s, 1H), 10.45 (s, 1H), 8.50-8.49 (m, 2H), 8.30 (d, J=2.9 Hz, 1H), 8.11 (d, J=9.0 Hz, 1H), 7.78 (dd, J=9.0, 2.9 Hz, 1H), 7.40 (d, J=2.6 Hz, 1H), 7.21 (dd, J=5.6, 2.7 Hz, 1H), 4.05-4.04 (m, 1H), 1.21 (s, 9H), 1.15 (d, J=6.5 Hz, 6H); MS (ESI) m/z: 400.2 (M+H+).

1. temperaturecooled to RT
2. washwashed with satd
3. extractionNaHCO3, water, and brine, and the combined aqueous washes were back-extracted with EtOAc
4. dry with materialThe combined organics were dried over Na2SO4
5. concentrationconcentrated to dryness
6. custompurified by silica gel chromatography (EtOAc/DCM)