反应详情

温度

130 °C

General Procedure G. To a solution of N-(3,4-difluorobenzyl)-2-isopropyl-6-hydroxy-1-(pyridin-2-ylmethyl)-1H-indole-3-carboxamide (Compound 220, 30 mg, 0.069 mmol) in N,N-dimethylacetamide (1.50 ml) stirring at room temperature, was added potassium hydroxide (80 mg, 1.43 mmol) and the reaction stirred for 5 minutes. 3-bromopyridine (0.05 mL, 0.08 g, 0.51 mmol) and then Copper powder (9.0 mg, 0.14 mmol) was then directly added and the resulting mixture heated at 120-140° C. for 18 h. The reaction was cooled to room temperature, quenched with water, extracted with EtOAc, washed with brine, dried over Na2SO4, and concentrated under reduced pressure. The residue was purified by flash column chromatography on silica gel (50% EtOAc-hexanes, 100 % EtOAc) to yield N-(3,4-difluorobenzyl)-2-isopropyl-1-(pyridin-2-ylmethyl)-6-(pyridin-3-yloxy)-1H-indole-3-carboxamide (Compound 222) as a yellow solid (2.3 mg). 1H NMR (300 MHz, METHANOL-d4) δ ppm 1.34 (d, J=7.0 Hz, 6 H), 4.59 (s, 2 H), 5.55 (s, 2 H), 6.72 (d, J=8.2 Hz, 1 H), 6.92 (dd, J=8.6, 2.2 Hz, 1 H), 7.02 (d, J=2.0 Hz, 1 H), 7.19-7.42 (m, 6 H), 7.62-7.74 (m, 2 H), 8.14-8.24 (m, 2 H), 8.49 (d, J=5.0 Hz, 1 H).

1. temperatureThe reaction was cooled to room temperature
2. customquenched with water
3. extractionextracted with EtOAc
4. washwashed with brine
5. dry with materialdried over Na2SO4
6. concentrationconcentrated under reduced pressure
7. customThe residue was purified by flash column chromatography on silica gel (50% EtOAc-hexanes, 100 % EtOAc)