反应详情

(3,5-Dimethyl-pyridin-2-ylmethyl)-{3-[1-(4-fluoro-phenyl)-1-methyl-ethyl]-pyridin-2-ylmethyl}-piperidin-4-yl-amine (0.270 g, 0.60 mmol) and 1,1′-carbonyldiimidazole (0.098 g, 0.60 mmol) were combined in THF (6 mL) and the mixture was stirred at room temperature for one hour. The solvent was removed under reduced pressure to give a colorless oil that was resuspended in DMF (5 mL), followed by addition of N,N-diisopropylamine (527 μL, 3.02 mmol) and NH2OH. HCl (0.168 g, 2.40 mmol). The mixture was stirred at room temperature for 16 hours and then the solvent was removed under reduced pressure. The yellow oil was resuspended in CH2Cl2 (30 mL), washed with brine (3×20 mL) and the organic layer was dried (Na2SO4), filtered and concentrated in vacuo to give a yellow oil. Purification by column chromatography on silica gel (CH2Cl2:MeOH:NH4OH, 85:10:5, v/v/v) afforded COMPOUND 318 as a white foamy solid (0.087 g, 27%). 1H NMR (CDCl3) δ 1.29-1.42 (m, 2H), 1.62 (s, 6H), 1.76 (d, 2H, J=12.0 Hz), 2.22 (s, 3H), 2.29 (s+m, 4H), 2.75-2.84 (m, 3H), 3.42 (m, 1H), 3.71 (br s, 2H), 4.02 (d, 2H, J=12.0 Hz), 6.87 (t, 2H, J=9.0 Hz), 7.07 (s, 2H), 7.15 (s, 1H), 7.23 (s, 1H), 7.23 (s, 1H), 7.81 (s, 1H), 7.88 (m, 1H), 8.15 (s, 1H), 8.54 (s, 1H). 13C NMR (CDCl3) δ 17.9, 18.2, 28.2, 31.0, 42.1, 46.3, 54.2, 115.0, 115.3, 118.0, 127.3, 129.6, 132.6, 136.9, 146.5, 150.7, 159.3. HPLC: 91%. ES-MS m/z 541 [M+H]+. Anal. Calcd. for C32H37N6OF.0.15 CH2Cl2: C, 69.78; H, 6.79; N, 15.19. Found: C, 69.74; H, 6.83; N, 15.03.

1. customThe solvent was removed under reduced pressure
2. customto give a colorless oil that
3. stirringThe mixture was stirred at room temperature for 16 hours
4. customthe solvent was removed under reduced pressure
5. washwashed with brine (3×20 mL)
6. dry with materialthe organic layer was dried (Na2SO4)
7. filtrationfiltered
8. concentrationconcentrated in vacuo
9. customto give a yellow oil
10. customPurification by column chromatography on silica gel (CH2Cl2