反应详情

tert-Butyl 4-(4-((4-((3-(2-ethoxy-2-oxoethyl)pyrazin-2-yl)ethynyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylate (I102) (I87 mg, 0.306 mmol) was dissolved in DMF (20 mL), triethylamine (0.1 mL) and a slurry of 10% Pd/C (0.100 g) in DMF (2 mL) was added. The mixture was purged with 3×vacuum/hydrogen cycles, and then stirred vigorously under a hydrogen atmosphere. After 17 hours the mixture was filtered through celite, and the celite washed with ethyl acetate (200 mL). The combined filtrates were washed with 1:1 water:saturated brine (4×100 mL), dried (sodium sulphate) and evaporated to give the title compound (I103) (142 mg, 76%) as a yellow oil; 1H NMR (400 MHz, d4-MeOD) δ 8.51 (d, J=0.6 Hz, 1H), 8.42 (d, J=2.6 Hz, 1H), 8.34 (d, J=2.6 Hz, 1H), 7.48 (d, J=8.3 Hz, 2H), 7.20-7.13 (m, 2H), 4.21 (dd, J=11.4, 1.8 Hz, 2H), 4.15 (q, J=7.1 Hz, 2H), 3.97 (s, 2H), 3.37 (s, 4H), 2.87 (br s), 2.70 (tt, J=11.9, 3.3 Hz, 1H), 1.83 (d, J=12.4 Hz, 2H), 1.59 (ddd, J=25.6, 12.9, 4.4 Hz, 2H), 1.48 (s, 9H), 1.21 (t, J=7.1 Hz, 3H). LCMS Method C: rt 6.76 min; m/z 615.1 [M+H]+, 559.1 [M−tBu+2H]+, 515.1 [M−Boc+2H]+.

1. customThe mixture was purged with 3×vacuum/hydrogen cycles
2. filtrationAfter 17 hours the mixture was filtered through celite
3. washthe celite washed with ethyl acetate (200 mL)
4. washThe combined filtrates were washed with 1:1 water
5. dry with materialsaturated brine (4×100 mL), dried (sodium sulphate)
6. customevaporated