反应详情

To a N,N-dimethylformamide (10 mL) suspension of sodium hydride (97%, 0.784 g, 32.7 mmol) was added methyl 2-oxoindoline-5-carboxylate (2.34 g, 12.3 mmol). The formed mixture was stirred for 10 min at room temperature followed by the addition of 4-[(6-chloro-1-oxidopyridin-3-yl)methyl]morpholine (1.87 g, 8.2 mmol). The resulting reaction mixture was set under N2 atmosphere and stirred for 1 h at 135° C. The N,N-dimethylformamide solution was diluted with saturated aqueous sodium hydrogen carbonate (30 mL) and extracted with chloroform, and ethyl acetate (containing 5% methanol). The combined organic phases were concentrated in vacuo. The remaining N,N-dimethylformamide was removed by co-evaporation with toluene. The residue was dissolved in ethyl acetate/chloroform, (150 mL, 2:1), and phosphorus trichloride (4.5 g, 33 mmol) was added. The reaction mixture was stirred for 1 h at 60° C., and then cooled to room temperature. The mixture was poured into a saturated aqueous sodium hydrogen carbonate solution followed by extraction of the aqueous phase with chloroform (4×). The combined organic extracts were concentrated in vacuo, and the residue was purified on a silica gel column using chloroform/methanol, (10:1), as the eluent to afford 1.05 g (35% yield) of the title compound as a yellow-brown solid: 1H NMR (DMSO-d6, 400 MHz) δ 10.83 (br s, 1H), 8.11 (s, 1H), 8.04 (s, 1H), 7.91 (d, J=8.0 Hz, 1H), 7.63 (t, J=8.0 Hz, 2H), 7.00 (d, J=8.0 Hz, 1H), 3.87 (s, 3H), 3.62 (br s, 4H), 3.41 (s, 2H), 2.42 (br s, 4H); MS (EI) m/z 368 (M++1).

1. customThe resulting reaction mixture
2. stirringstirred for 1 h at 135° C
3. extractionextracted with chloroform, and ethyl acetate (containing 5% methanol)
4. concentrationThe combined organic phases were concentrated in vacuo
5. customThe remaining N,N-dimethylformamide was removed by co-evaporation with toluene
6. dissolutionThe residue was dissolved in ethyl acetate/chloroform, (150 mL, 2:1),
7. stirringThe reaction mixture was stirred for 1 h at 60° C.
8. temperaturecooled to room temperature
9. extractionfollowed by extraction of the aqueous phase with chloroform (4×)
10. concentrationThe combined organic extracts were concentrated in vacuo
11. customthe residue was purified on a silica gel column