反应详情

Heat a mixture of 4-chloro-6-(3-chloro-4-fluoro-phenyl)-2-(2-methyl-pyrrolidin-1-yl)-pyrimidine (210 mg), 1-(3-Methyl-5-nitro-pyridin-2-yl)-piperazine, and DIEA (185 mg, 1.44 mmol) in DMA at 120° C. for 16 h. Cool to room temperature and partition between EtOAc and 1N NaOH. Wash with water, dry the solution (Na2SO4), and concentrate under reduced pressure. Purify the residue by flash column eluting with EtOAc to afford the title compound as a light-yellow solid. 1H NMR (400 MHz, CDCl3): δ 1.30 (t, 3H, J=6.4 Hz, CH3); 1.69 (m, 1H, CH2CH2); 1.91 (m, 1H, CH2CH2); 2.06 (m, 2H, CH2CH2); 2.28 (s, 3H, Ar—CH3); 3.10 (m, 4H); 3.47 (br, 2H, NH2); 3.68 (m, 4H); 3.77 (m, 4H); 4.34 (m, 1H); 6.25 (s, 1H, Ar—H); 6.88 (d, J=2.0 Hz, 1H); 7.18 (m, 1H); 7.70 (d, 1H, J=3.2 Hz); 7.89 (m, 1H); 8.07 (m, 1H).

1. temperatureHeat
2. custompartition between EtOAc and 1N NaOH
3. washWash with water
4. dry with materialdry the solution (Na2SO4)
5. concentrationconcentrate under reduced pressure
6. customPurify the residue by flash column
7. washeluting with EtOAc