反应详情

To a solution of tert-butyl 4-(4-((4-(2-(2-amino-2-oxoethyl)phenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)-3-methoxyphenyl)piperazine-1-carboxylate (I8) (0.276 g, 0.449 mmol) in dichloromethane (8 mL), was added trifluoroacetic acid (0.669 mL, 8.98 mmol) and the resulting mixture was stirred under a nitrogen atmosphere for 18 hours. The solvents were evaporated in vacuo to give a yellow residue which was dissolved in 3:1 chloroform/2-propanol and 1 M aqueous sodium hydroxide solution. The aqueous layer was extracted with 3:1 chloroform/2-propanol (3×15 mL) and the combined organic extracts were washed with water, brine, dried (magnesium sulfate), filtered and evaporated to give the title compound (1) (0.229 g, 99%) as a yellow foam; 1H NMR (300 MHz, d6-DMSO) δ 2.87-3.10 (m, 12 H), 3.46 (s, 2 H), 3.78 (s, 3 H), 4.32 (d, 1 H, J=4.2 Hz), 6.48 (dd, 1 H, J=2.2, 8.7 Hz), 6.61 (d, 1 H, J=2.1 Hz), 6.88 (brs, 1 H), 7.15-7.30 (m, 4 H), 7.38 (brs, 1 H), 7.46 (brs, 1 H), 8.51 (s, 1 H) and 8.81 (s, 1 H). LCMS Method B: rt 5.65 min; m/z 515.4 [M+H]+.

1. customThe solvents were evaporated in vacuo
2. customto give a yellow residue which
3. extractionThe aqueous layer was extracted with 3:1 chloroform/2-propanol (3×15 mL)
4. washthe combined organic extracts were washed with water, brine
5. dry with materialdried (magnesium sulfate)
6. filtrationfiltered
7. customevaporated