反应详情

温度

160 °C

Benzylamine (9.1 mL, 83.8 mmol, 20 eq) was added to 4-(2-chloropyridin-4-yloxy)-3-fluorobenzenamine (Compound B of Example 20, 1.0 g, 4.19 mmol, 1.0 eq), copper powder (0.266 g, 4.19 mmol, 1.0 eq) and K2CO3 (0.578 g, 4.19 mmol, 1.0 eq) in a sealed tube and the reaction mixture was heated to 160° C. for 12 h. The reaction mixture was cooled to room temperature and quenched with saturated aqueous NaCl solution. The solution was extracted with ethyl acetate (3×100 mL), the combined organic extracts dried (Na2SO4), filtered and concentrated in vacuo. The residue was purified by preparative reverse phase HPLC (YMC C-18 ODS-A S10 50×500 mm, eluting 10-90% aqueous MeOH with 0.1% TFA, 30 minute gradient) and the appropriate fractions were concentrated in vacuo. The concentrate was neutralized with saturated aqueous NaHCO3 solution and extracted with CH2Cl2 (3×100 mL). The combined organic extracts were dried (Na2SO4), filtered and concentrated in vacuo to afford the title compound (0.675 g, 52%) as a solid. 1H NMR (CD3OD) δ 7.78-7.80 (m, 1H), 7.28-7.30 (m, 5H), 6.80-6.90 (m, 1H), 6.52-6.55 (m, 2H), 6.18-6.20 (m, 1H), 5.87-5.88 (m, 1H), 4.40 (s, 2H); MS(ESI+) m/z 310 (M+H)+; HRMS(ESI+) calcd.: 310.1356, found: 310.1360.

1. temperatureThe reaction mixture was cooled to room temperature
2. customquenched with saturated aqueous NaCl solution
3. extractionThe solution was extracted with ethyl acetate (3×100 mL)
4. dry with materialthe combined organic extracts dried (Na2SO4)
5. filtrationfiltered
6. concentrationconcentrated in vacuo
7. customThe residue was purified by preparative reverse phase HPLC (YMC C-18 ODS-A S10 50×500 mm, eluting 10-90% aqueous MeOH with 0.1% TFA, 30 minute gradient)
8. concentrationthe appropriate fractions were concentrated in vacuo
9. extractionextracted with CH2Cl2 (3×100 mL)
10. dry with materialThe combined organic extracts were dried (Na2SO4)
11. filtrationfiltered
12. concentrationconcentrated in vacuo