反应详情

温度

160 °C

A mixture of 6-methyl-2,3-pyridinediamine (2.1 g, 17 mmol), 2-chloro-6-(trifluoromethyl)nicotinic acid (3.8 g, 17 mmol) and Cu (1 g, 17 mmol) in HOC2H5OBu was stirred at 160° C. overnight. When LCMS showed the reaction was complete, the mixture was filtered and concentrated to give a crude product, which was dissolved in THF (100 ml) in a flask equipped with a condenser and a nitrogen balloon. A solution of borane-Me2S (10 M, 10 ml, 0.1 mol) was added dropwise, and the resulting mixture was refluxed for 20 h before it was cooled, acidified to pH=1 with concentrated HCl, and refluxed for another 3 hours. The mixture was neutralized to pH=8 with saturated aqueous sodium bicarbonate, and the product was extracted with ethyl acetate (200 ml×3). The combined organic phases were washed with water and brine, dried over sodium sulfate and concentrated under reduced pressure. The residue was purified on silica gel eluting with pet ether:ethyl acetate (10:1) to afford the product 2-methyl-7-(trifluoromethyl)-10,11-dihydro-5H-dipyrido[2,3-b:2′,3′-e][1,4]diazepine. 1H-NMR A27111 H02393-117-1 (400 MHz, DMSO) δ 10.83 (br, 1H, NH), 7.45 (d, J=7.6 Hz, 1H, Ar—H), 7.40 (d, J=8 Hz, 1H, Ar—H), 7.16 (d, J=7.6 Hz, 1H, Ar—H), 6.61 (t, J=7.6 Hz, 1H, Ar—H), 4.23 (s, 2H, CH2), 2.51 (s, 3H, CH3).

1. filtrationthe mixture was filtered
2. concentrationconcentrated
3. customto give a crude product, which
4. customequipped with a condenser
5. temperaturethe resulting mixture was refluxed for 20 h before it
6. temperaturewas cooled
7. temperaturerefluxed for another 3 hours
8. extractionthe product was extracted with ethyl acetate (200 ml×3)
9. washThe combined organic phases were washed with water and brine
10. dry with materialdried over sodium sulfate
11. concentrationconcentrated under reduced pressure
12. customThe residue was purified on silica gel eluting with pet ether:ethyl acetate (10:1)