反应详情

Heat a solution of 4-[4-(3-chloro-6-methoxy-pyridin-2-yl)-2-methyl-piperazin-1-yl]-6-(4-fluoro-phenyl)-2-(2-methyl-pyrrolidin-1-yl)-pyrimidine (120 mg, 0.241 mmol) in concentrated HCl at 90° C. for 24 hours. Cool to room temperature, adjust the pH to 7, and extract with EtOAc. Wash with brine, dry the solution (Na2SO4), and concentrate under reduced pressure. Purify the residue by flash column chromatography eluting with EtOAc:Hexanes (1:4) to afford 5-chloro-6-{4-[6-(4-fluoro-phenyl)-2-(2-methyl-pyrrolidin-1-yl)-pyrimidin-4-yl]-3-methyl-piperazin-1-yl}-pyridin-2-ol as an off-white solid. 1H NMR (300 MHz, CDCl3): δ1.32 (m, 6H, 2×CH3); 1.69 (m, 1H, CH2CH2); 1.91 (m, 1H, CH2CH2); 2.04 (m, 2H, CH2CH2); 3.06 (m, 1H); 3.24 (m, 1H); 3.36 (m, 1H); 3.67 (m, 4H); 4.33 (m, 2H); 4.71 (m, 1H); 6.22 (m, 2H); 7.10 (m, 2H); 7.45 (d, J=8.7 Hz, 1H); 8.01 (m, 2H); 9.27 (br, 1H, OH).

1. extractionextract with EtOAc
2. washWash with brine
3. dry with materialdry the solution (Na2SO4)
4. concentrationconcentrate under reduced pressure
5. customPurify the residue by flash column chromatography
6. washeluting with EtOAc:Hexanes (1:4)