反应详情

温度

0 °C

To a cooled mixture of (2-chloro-ethyl)-dimethyl-amine hydrochloride (116 mg, 0.81 mmol) in DMF, add Cs2CO3 (526 mg, 1.62 mmol) and stir at 0° C. for 30 min. Add 6-{4-[6-(3-chloro-4-fluoro-phenyl)-2-(2-methyl-pyrrolidin-1-yl)-pyrimidin-4-yl]-piperazin-1-yl}-5-methyl-pyridin-3-ol (78 mg, 0.16 mmol) and NaI (29 mg, 0.16 mmol). Stir the mixture at room temperature for 1 h and then for 2 h at 45° C. Partition between EtOAc and water. Wash with brine, dry the solution (Na2SO4), and concentrate under reduced pressure. Purify the residue by flash column chromatography eluting with DCM:MeOH:NH4OH (90:10:1) to afford the title compound. 1H NMR (300 MHz, CDCl3): δ1.29 (t, 3H, J=6.3 Hz, CH3); 1.69 (m, 1H, CH2CH2); 1.91 (m, 1H, CH2CH2); 2.05 (m, 2H, CH2CH2); 2.32 (s, 3H, Ar—CH3); 2.33 (s, 6H, N(CH3)2); 2.71 (t, J=5.7 Hz, 2H); 3.13 (m, 4H); 3.64 (m, 4H); 3.80 (m, 4H); 4.06 (t, J=5.7 Hz, 2H); 4.34 (m, 1H); 6.25 (s, 1H, Ar—H); 7.10 (d, J=2.7 Hz, 1H); 7.18 (m, 1H); 7.89 (m, 2H); 8.04 (m, 1H).

1. stirringStir the mixture at room temperature for 1 h
2. waitfor 2 h at 45° C
3. customPartition between EtOAc and water
4. washWash with brine
5. dry with materialdry the solution (Na2SO4)
6. concentrationconcentrate under reduced pressure
7. customPurify the residue by flash column chromatography
8. washeluting with DCM:MeOH:NH4OH (90:10:1)