反应详情

A solution of TFA (0.84 mL, 11 mmol) and tert-butyl 4-(4-((4-(2-(1-amino-1-oxobutan-2-yl)phenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylate (A2) (168 mg, 0.275 mmol) in DCM (20 mL) was stirred for 24 hours at room temperature under a nitrogen atmosphere. The volatiles were removed in vacuo and the residue was taken up in MeOH and loaded onto an SCX cartridge (10 g). The column was eluted with 5 column volumes of MeOH and then 5 column volumes of 5% v/v aqueous ammonia in MeOH to elute the amine product. The ammoniacal filtrate was evaporated under reduced pressure and the residue was taken up in DCM (˜2 mL). Cyclohexane (˜10 mL) was added and the resulting suspension sonicated for 10 minutes. The precipitate was isolated by filtration to give the title compound 1 as an off-white solid (100 mg, 71%); 1H NMR (400 MHz, d6-DMSO) δ 10.14 (s, 1H), 8.67 (s, 1H), 7.66 (d, J=8.6 Hz, 2H), 7.51-7.43 (m, 1H), 7.31 (s, 1H), 7.22-7.10 (m, 5H), 6.87 (s, 1H), 3.61 (dd, J=8.8, 6.1 Hz, 1H), 3.22-2.89 (m, 6H), 2.62-2.53 (m, 3H), 2.07-1.91 (m, 1H), 1.67 (d, J=12.0 Hz, 2H), 1.62-1.42 (m, 3H), 0.87-0.80 (m, 3H). LCMS-A: rt 4.973 min; m/z 512 [M+H]+.

1. customThe volatiles were removed in vacuo
2. washThe column was eluted with 5 column volumes of MeOH
3. wash5 column volumes of 5% v/v aqueous ammonia in MeOH to elute the amine product
4. customThe ammoniacal filtrate was evaporated under reduced pressure
5. additionCyclohexane (˜10 mL) was added
6. customthe resulting suspension sonicated for 10 minutes
7. customThe precipitate was isolated by filtration