反应详情

A mixture of Example C1 (0.15 g, 0.455 mmol), cyanoacetic acid (0.080 mL, 1.206 mmol), TBTU (0.258 g, 0.804 mmol) and DIEA (0.35 mL, 2.009 mmol) in DMF (5 mL) was stirred at RT overnight, 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 N-((5-((2-(2-cyanoacetamido)pyridin-4-yl)oxy)pyridin-2-yl)carbamoyl)pivalamide (126 mg, 79%). 1H NMR (400 MHz, DMSO-d6): δ 11.24 (s, 1H), 10.92 (s, 1H), 10.44 (s, 1H), 8.26 (d, J=2.9 Hz, 1H), 8.22 (d, J=5.8 Hz, 1H), 8.10 (d, J=9.0 Hz, 1H), 7.75 (dd, J=9.0, 2.9 Hz, 1H), 7.56 (s, 1H), 6.76 (dd, J=5.7, 2.4 Hz, 1H), 3.93 (s, 2H), 1.21 (s, 9H); MS (ESI) m/z: 397.2 (M+H+).

1. extractionextracted with DCM (4×)
2. washthe combined organics were washed with brine
3. dry with materialdried over Na2SO4
4. concentrationconcentrated to dryness
5. custompurified via preparative TLC (MeOH/DCM/TEA)