反应详情

温度

100 °C

To a solution of 5-bromo-2-methyl-3-nitro-pyridine (1.58 g, 7.28 mmol) [prepared according to WO 2006/103449] in dimethylformamide (10 mL) was added dimethylformamide dimethyl acetal (1.65 mL, 12.37 mmol). The reaction mixture was stirred at 100° C. for 1 h, then cooled to room temperature and concentrated in vacuo. The residue was dissolved in glacial acetic acid (25 mL) and iron powder (3.25 g, 58.24 mmol) was added. The reaction mixture was stirred at 100° C. for 21 h, then it was cooled to room temperature. Methanol (25 mL) was added and the suspension was filtered and washed with Methanol. The filtrate was concentrated in vacuo. The residue was partitioned between saturated aqueous sodium bicarbonate and ethyl acetate. The organic layer was separated, dried over sodium sulfate, filtered, and adsorbed on silica gel. Purification on silica gel by flash chromatography using a gradient of 0-70% ethyl acetate/hexane provided 869 mg of the title compound as an ivory solid (60% yield): 1H NMR (DMSO-d6): δ 6.77 (s, 1H), 7.68 (s, 1H), 8.00 (s, 1H), 8.36 (s, 1H), 11.46 (broad s, 1H); MS (m/z) 197, 199 [M+H+]+.

1. temperaturecooled to room temperature
2. concentrationconcentrated in vacuo
3. dissolutionThe residue was dissolved in glacial acetic acid (25 mL)
4. stirringThe reaction mixture was stirred at 100° C. for 21 h
5. temperatureit was cooled to room temperature
6. filtrationthe suspension was filtered
7. washwashed with Methanol
8. concentrationThe filtrate was concentrated in vacuo
9. customThe residue was partitioned between saturated aqueous sodium bicarbonate and ethyl acetate
10. customThe organic layer was separated
11. dry with materialdried over sodium sulfate
12. filtrationfiltered
13. customPurification on silica gel by flash chromatography