反应详情

温度

60 °C

To a RT solution of 2-fluoro-N-methyl-4-(3-(piperidin-4-yl)pyrazin-2-yl)benzamide trihydrochloride (1.00 g, 3.18 mmol, prepared according to Step 2 of Example 1) and triethylamine (2.00 ml, 14.35 mmol) in DMSO (10 ml) was added a solution of 7-fluoroquinolin-2-yl trifluoromethanesulfonate (1.10 g, 3.73 mmol, prepared according to Step 3 of Example 2) in DMSO (2 mL). The reaction mixture was heated at 60° C. for 2.5 h. The reaction was cooled RT and diluted with water. The mixture was extracted with CH2Cl2 (3×). The combined organic layers were washed with brine and dried over Na2SO4. The solution was filtered and the solution was evaporated onto silica gel and purified by flash chromatography (Isco (80 gram)) eluting with EtOAc:hexanes (0:1→3:1). The fractions containing product were concentrated in vacuo and the residue was stirred vigorously over Et2O for 3 h. The solid was filtered, washed with Et2O and dried to give 674 mg (46%) of the desired product. m/z=460 (M+1). 1H NMR (300 MHz, DMSO-d6) δ ppm 8.62 (d, J=2.34 Hz, 1H), 8.59 (d, J=2.34 Hz, 1H), 8.39 (br. s., 1H), 8.04 (d, J=9.21 Hz, 1H), 7.69-7.83 (m, 2H), 7.45-7.58 (m, 2H), 7.18-7.28 (m, 2H), 7.08 (td, J=8.77, 2.63 Hz, 1H), 4.66 (d, J=13.30 Hz, 2H), 3.13-3.29 (m, 1H), 2.86-3.03 (m, 2H), 2.82 (d, J=4.68 Hz, 3H), 1.72-1.97 (m, 4H).

1. temperatureThe reaction was cooled RT
2. extractionThe mixture was extracted with CH2Cl2 (3×)
3. washThe combined organic layers were washed with brine
4. dry with materialdried over Na2SO4
5. filtrationThe solution was filtered
6. customthe solution was evaporated onto silica gel
7. custompurified by flash chromatography (Isco (80 gram))
8. washeluting with EtOAc:hexanes (0:1→3:1)
9. additionThe fractions containing product
10. concentrationwere concentrated in vacuo
11. filtrationThe solid was filtered
12. washwashed with Et2O
13. customdried