反应详情

N,N-Diisopropylethylamine (18.0 μL, 0.103 mmol) was added to a solution of 2-(2-(2-(2-((4-(Piperidin-3-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)pyridin-3-yl)acetamide (39) (17 mg, 0.034 mmol) in DMF (5 mL). The mixture was stirred for 5 min then bromoethane (4.0 μL, 0.051 mmol) was added and stirring was continued for 24 h at room temperature. A further portion of bromoethane (4.0 μL, 0.051 mmol) was added and the reaction mixture was stirred for an additional 16 hours at room temperature. The volatiles were evaporated in vacuo and the residue partitioned between ethyl acetate (10 mL) and saturated aqueous sodium hydrogen carbonate (10 mL). The layers were separated and the aqueous layer extracted with ethyl acetate (2×10 mL). The combined organic layers were washed with water (10 mL), brine (10 mL) and dried over Na2SO4. Filtration then removal of the solvent under reduced pressure afforded a beige solid which was purified by mass-directed preparative HPLC to afford the title compound (40) (6.2 mg, 36%) as a white solid; 1H NMR (400 MHz, d4-MeOH) δ 8.54 (s, 1H), 8.38 (dd, J=4.8, 1.5 Hz, 1H), 7.69-7.66 (m, 3H), 7.28-7.19 (m, 3H), 3.68 (s, 2H), 3.59-3.46 (m, 2H), 3.38-3.22 (m, partially obscured by d4-MeOH), 3.19-3.08 (m, 2H), 3.04-2.80 (m, 3H), 2.12-1.99 (m, 2H), 1.99-1.70 (m, 2H), 1.34 (t, J=7.3 Hz, 3H). LCMS Method C: rt=4.20 min, m/z=513.2 [M+H]+, 511.2 [M−H]−.

1. stirringstirring
2. waitwas continued for 24 h at room temperature
3. stirringthe reaction mixture was stirred for an additional 16 hours at room temperature
4. customThe volatiles were evaporated in vacuo
5. customthe residue partitioned between ethyl acetate (10 mL) and saturated aqueous sodium hydrogen carbonate (10 mL)
6. customThe layers were separated
7. extractionthe aqueous layer extracted with ethyl acetate (2×10 mL)
8. washThe combined organic layers were washed with water (10 mL), brine (10 mL)
9. dry with materialdried over Na2SO4
10. filtrationFiltration
11. customremoval of the solvent under reduced pressure
12. customafforded a beige solid which
13. customwas purified by mass-directed preparative HPLC