反应详情

To a solution of 2-bromo-3-nitrobenzoic acid (500 mg, 2.03 mmol) in DMF (3 mL) was added cyclopropylamine (0.14 mL, 2.03 mmol), N-ethyl-N-isopropyl-propan-2-amine (0.34 mL, 2.03 mmol) and (1H-benzo[d][1,2,3]triazol-1-yloxy)-tripyrrolidin-1-ylphosphonium hexafluorophosphate(V) (1.27 g, 2.44 mmol). The resulting mixture was stirred at rt for 24 h. The reaction mixture was diluted with EtOAc, washed with water, brine, dried over magnesium sulfate, and concentrated in vacuo. The residue was subjected to flash chromatography on a silica gel column using 0 to 100% gradient of EtOAC:DCM (1:1) in DCM as eluent to give a crude product mixture. To the crude mixture in THF (10 mL) was added cyclopropylamine (0.141 mL, 2.03 mmol) and the resulting mixture was heated under N2 at 60° C. for 18 h. The reaction mixture was diluted with EtOAc, washed with water, brine and dried over magnesium sulfate. After being concentrated in vacuo, the residue was purified by flash chromatography on silica gel using 0 to 100% gradient of EtOAC:DCM (1:1) in DCM as eluent to give N-cyclopropyl-2-(cyclopropylamino)-3-nitrobenzamide: 1H NMR (400 MHz, CDCl3) δ 8.27 (1H, s), 8.01 (1H, d, J=8.0 Hz), 7.45 (1H, d, J=8.0 Hz), 6.62 (1H, t, J=8.0 Hz), 5.98 (1H, s), 2.90-2.65 (2H, m), 0.90-0.78 (2H, m), 0.75-0.65 (2H, m), 0.58-0.50 (2H, m), 0.48-0.40 (2H, m); LC-MS (ESI) m/z 262.1 [M+H]+.

1. washwashed with water, brine
2. dry with materialdried over magnesium sulfate
3. concentrationconcentrated in vacuo
4. customDCM (1:1) in DCM as eluent to give a crude product mixture
5. temperaturethe resulting mixture was heated under N2 at 60° C. for 18 h
6. washwashed with water, brine
7. dry with materialdried over magnesium sulfate
8. concentrationAfter being concentrated in vacuo
9. customthe residue was purified by flash chromatography on silica gel using 0 to 100% gradient of EtOAC