反应详情

A solution of 1-pyrrolidinylacetic 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 silica gel chromatography (MeOH/EtOAc). The material was further purified via preparative TLC (MeOH/DCM/TEA) to afford N-((5-((2-(2-(pyrrolidin-1-yl)acetamido)pyridin-4-yl)oxy)pyridin-2-yl)carbamoyl)pivalamide (31 mg, 15%). 1H NMR (400 MHz, DMSO-d6): δ 11.23 (s, 1H), 10.44 (s, 1H), 9.98 (s, 1H), 8.26 (d, J=2.9 Hz, 1H), 8.20 (d, J=5.8 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), 6.74 (dd, J=5.8, 2.4 Hz, 1H), 3.27 (s, 2H), 2.58 (s, 4H), 1.73-1.71 (m, 4H), 1.21 (s, 9H); MS (ESI) m/z: 441.2 (M+H+).

1. concentrationconcentrated to dryness
2. extractionextracted with DCM (4×)
3. washthe combined organics were washed with brine
4. dry with materialdried over Na2SO4
5. concentrationconcentrated to dryness
6. custompurified via silica gel chromatography (MeOH/EtOAc)
7. customThe material was further purified via preparative TLC (MeOH/DCM/TEA)