反应详情

4-Methoxypiperidine (1.31 g, 11 mmol, 1 equiv) was added via syringe to a mixture of 2-chloro-4,6-dimethoxy-5-nitropyrimidine (2.5 g, 11 mmol) and diisopropylethylamine (5.97 mL, 34 mmol, 3 equiv) in THF (60 mL). The reaction mixture was stirred at RT for 1 h, and then additional 4-methoxypiperidine (0.6 g, 5 mmol, 0.47 equiv) was added via syringe. The mixture was stirred for another 1 h and then diluted with water and extracted with ethyl acetate (2×). The organic extracts were dried over sodium sulfate, filtered and concentrated. The crude material was purified using a Biotage Isolera One (SiO2, 80 g, 0-80% EtOAc in heptane gradient) to afford 2.99 g (88%) of 4,6-dimethoxy-2-(4-methoxypiperidin-1-yl)-5-nitropyrimidine as a yellow solid. 1H NMR (400 MHz, CDCl3) δ 4.14 (ddd, J=13.2, 7.5, 3.9 Hz, 2H) 3.99 (s, 6H) 3.63 (ddd, J=13.2, 8.5, 3.8 Hz, 2H) 3.51 (tt, J=7.4, 3.6 Hz, 1H) 3.40 (s, 3H) 1.86-1.96 (m, 2H) 1.61-1.70 (m, 2H). LCMS m/z=299.1 (M+1).

1. stirringThe mixture was stirred for another 1 h
2. extractionextracted with ethyl acetate (2×)
3. dry with materialThe organic extracts were dried over sodium sulfate
4. filtrationfiltered
5. concentrationconcentrated
6. customThe crude material was purified