反应详情

tert-Butyl 4-(4-((4-(2-(5-(2-amino-2-oxoethyl)pyrimidin-4-yl)ethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylate (I114) (0.076 g, 0.13 mmol) was dissolved in DCM (5 mL) under an atmosphere of nitrogen. Trifluoroacetic acid (0.298 mL, 3.89 mmol) was added to the solution and the reaction was stirred at room temperature for 23 hours. Volatiles were removed in vacuo, EtOAc (70 mL) and 2 M aq. NaOH (70 mL) were added to the residue and the layers were separated. The aqueous layer was extracted with EtOAc (2×70 mL), the combined organics were washed with brine (2×50 mL), dried (MgSO4), filtered and concentrated in vacuo to give a pale yellow gum. Methanol (˜5 mL) and cyclohexane (˜15 mL) were added to the product, some of the volatiles were removed in vacuo (˜50%) which gave a yellow oil that separated from the solvent solution and was carefully transferred to a new flask with a pipette. The removed solution was concentrated in vacuo and then further dried under high-vacuum to give a pale yellow gum. Diethyl ether (5 mL) and methanol (1 mL) were added and the solution was concentrated in vacuo. The process was repeated twice with diethyl ether to give the title compound (29) (35 mg, 56% yield) as a pale yellow solid; 1H NMR (400 MHz, d4-MeOD) δ 8.91 (s, 1H), 8.53-8.50 (m, 2H), 7.52 (d, J=8.2 Hz, 2H), 7.21-7.16 (m, 2H), 3.70 (s, 2H), 3.42-3.34 (m, 4H), 3.27-3.20 (m, 2H), 2.84 (td, J=12.5, 2.6 Hz, 2H), 2.70 (tt, J=12.2, 3.9 Hz, 1H), 1.89 (d, J=13.7 Hz, 2H), 1.72 (ddd, J=16.4, 12.9, 4.0 Hz, 2H). LCMS Method C: rt 4.46 min; m/z 486.1 [M+H]+.

1. customVolatiles were removed in vacuo, EtOAc (70 mL) and 2 M aq. NaOH (70 mL)
2. additionwere added to the residue
3. customthe layers were separated
4. extractionThe aqueous layer was extracted with EtOAc (2×70 mL)
5. washthe combined organics were washed with brine (2×50 mL)
6. dry with materialdried (MgSO4)
7. filtrationfiltered
8. concentrationconcentrated in vacuo
9. customto give a pale yellow gum
10. customsome of the volatiles were removed in vacuo (˜50%) which
11. customgave a yellow oil
12. customthat separated from the solvent solution
13. customwas carefully transferred to a new flask with a pipette
14. concentrationThe removed solution was concentrated in vacuo
15. customfurther dried under high-vacuum
16. customto give a pale yellow gum
17. concentrationthe solution was concentrated in vacuo