反应详情

温度

140 °C

To a stirred solution of compound 2 (100 mg, 0.24 mmol) in toluene (5 mL) were added 3-bromopyridine (59.3 mg, 0.36 mmol), trans-1,2-diaminocyclohexane (11.2 mg, 0.098 mmol), K3PO4 (130 mg, 0.65 mmol), CuI (4.6 mg, 0.024 mmol) at RT under argon in a sealed tube. The solution was purged with argon; heated to 140° C. and stirred for 40 h. The mixture was cooled to RT, added n-hexane (6 mL), stirred for 5 minutes and then filtered. The filtrate was diluted with water (20 mL) and extracted with EtOAc (2×50 mL). The combined organic extracts were washed with water and brine solution, dried (Na2SO4), filtered and concentrated under reduced pressure to obtain the crude. This was purified (silica gel; 5-10% EtOAc/hexanes) to afford compound 3 (10 mg, 8.4%) as a pale brown solid. 1H NMR (400 MHz, CDCl3): 8.77 (br s, 2H), 7.81 (d, J=8.0 Hz, 1H), 7.68-7.62 (m, 1H), 7.53-7.50 (m, 1H), 7.25-7.23 (m, 1H), 7.17-7.11 (m, 1H), 6.96 (t, J=7.6 Hz, 1H), 6.82 (dt, J=8.4, 1.6 Hz, 1H), 4.40 (q, 2H), 1.65-1.60 (m, 1H), 1.41 (t, J=7.2 Hz, 3H), 0.91-0.82 (m, 4H); LC-MS (ESI): m/z 485.5 (M+H+).

1. customThe solution was purged with argon
2. temperatureThe mixture was cooled to RT
3. additionadded n-hexane (6 mL)
4. stirringstirred for 5 minutes
5. filtrationfiltered
6. additionThe filtrate was diluted with water (20 mL)
7. extractionextracted with EtOAc (2×50 mL)
8. washThe combined organic extracts were washed with water and brine solution
9. dry with materialdried (Na2SO4)
10. filtrationfiltered
11. concentrationconcentrated under reduced pressure
12. customto obtain the crude
13. customThis was purified (silica gel; 5-10% EtOAc/hexanes)