反应详情

温度

100 °C

Example 100. A solution of 9-(isoxazol-5-yl)-3,4,7,8-tetrahydro-[1,4]diazepino[7,1-a]isoquinoline-2,5-dione (90 mg, 0.31 mmol) in DCE (4 mL) was treated with POCl3 (57 μL, 0.61 mmol) and the mixture was heated to 100° C. for 1 h. The mixture was then allowed to cool to RT, poured onto H2O and extracted with DCM. The org. phases were then dried over Na2SO4, filtered and concentrated in vacuo. The brown residue obtained was taken up in DCE (4 mL) and 4-cyclopropyl-1H-imidazole (50 mg, 0.46 mmol) and pyridine (74 μL, 0.91 mmol) were then added. The mixture was heated to 110° C. for 1 h, and then allowed to cool to RT, poured onto H2O and extracted with DCM. The org. layers were then dried over Na2SO4, filtered and concentrated in vacuo. Purification by flash chromatography (SiO2, cHex/AcOEt 100:0 to 0:100 and DCm/MeOH 99:1 to 90:10) afforded the title compound (42 mg) as a pale red solid. UPLC-MS: MS 386.2 (M+H+); UPLC rt 0.85 min. 1H NMR (400 MHz, CHLOROFORM-d): δ ppm 0.67-0.79 (m, 2 H); 0.80-0.91 (m, 2 H); 1.80-1.91 (m, 1 H); 3.17 (t, J=6.06 Hz, 2 H); 3.90 (t, J=6.19 Hz, 2 H); 4.37 (s, 2 H); 6.47 (s, 1 H); 6.63 (s, 1 H); 7.18 (s, 1 H); 7.50 (t, J=7.83 Hz, 1 H); 7.70-7.83 (m, 2 H); 7.88 (s, 1 H); 8.38 (s, 1 H).

1. temperatureto cool to RT
2. additionpoured onto H2O
3. extractionextracted with DCM
4. dry with materialphases were then dried over Na2SO4
5. filtrationfiltered
6. concentrationconcentrated in vacuo
7. customThe brown residue obtained
8. temperatureThe mixture was heated to 110° C. for 1 h
9. temperatureto cool to RT
10. additionpoured onto H2O
11. extractionextracted with DCM
12. dry with materiallayers were then dried over Na2SO4
13. filtrationfiltered
14. concentrationconcentrated in vacuo
15. customPurification by flash chromatography (SiO2, cHex/AcOEt 100:0 to 0:100 and DCm/MeOH 99:1 to 90:10)