反应详情

To a stirred solution of tert-butyl 3-(4-(4-(2-(1-carbamoylcyclopropyl)phenethyl)-5-chloropyrimidin-2-ylamino)-1H-pyrazol-1-yl)pyrrolidine-1-carboxylate A21 (0.164 g, 0.297 mmol) in DCM (5 mL) was added 4 M HCl solution in 1,4-dioxane (0.223 mL). The mixture was stirred for 5 hours before additional 4 M HCl in dioxane (3 eq.) was added and the mixture stirred for another 16 hours. Another portion of 4 M HCl in 1,4-dioxane (2 mL) was added and the mixture was stirred for 16 hours. The solvent was removed and the residue was diluted with 1 M HCl aq. (˜5 mL) and washed with EtOAc (2×10 mL). The aqueous layer was basified with 1 M NaOH and extracted with EtOAc (3×10 mL). The combined organics were dried (MgSO4), filtered and concentrated in vacuo to give a crude white paste that was purified by flash chromatography (0-100% EtOAc in cyclohexane) to give the title compound as a red oil. Further purification by HPLC (Gradient: 20-100%, Acetonitrile 0.1% formic acid in water 0.1% formic acid, 12 min) gave the title compound 20 as a clear gum (0.012 g, 9% yield). 1H NMR (300 MHz, MeOD) δ 1.14 (d, J=3.30 Hz, 2H), 1.64 (d, J=3.30 Hz, 2H), 2.32-2.44 (m, 1H), 2.46-2.65 (m, 1H), 3.12-3.26 (m, 4H), 3.43-3.54 (m, 1H), 3.60-3.80 (m, 3H), 5.21-5.32 (m, 1H), 7.23-7.45 (m, 4H), 7.64 (s, 1H), 8.08 (m, 1H), 8.29 (m, 1H). LCMS-C: rt 4.29 min; m/z 452 [M+H]+.

1. additionwas added
2. stirringthe mixture was stirred for 16 hours
3. customThe solvent was removed
4. additionthe residue was diluted with 1 M HCl aq. (˜5 mL)
5. washwashed with EtOAc (2×10 mL)
6. extractionextracted with EtOAc (3×10 mL)
7. dry with materialThe combined organics were dried (MgSO4)
8. filtrationfiltered
9. concentrationconcentrated in vacuo
10. customto give a crude white paste that
11. customwas purified by flash chromatography (0-100% EtOAc in cyclohexane)