[CH3:1][O:2][CH:3]1[CH2:8][CH2:7][NH:6][CH2:5][CH2:4]1.Cl[C:10]1[N:15]=[C:14]([O:16][CH3:17])[C:13]([N+:18]([O-:20])=[O:19])=[C:12]([O:21][CH3:22])[N:11]=1.C(N(C(C)C)CC)(C)C>C1COCC1.O>[CH3:17][O:16][C:14]1[C:13]([N+:18]([O-:20])=[O:19])=[C:12]([O:21][CH3:22])[N:11]=[C:10]([N:6]2[CH2:7][CH2:8][CH:3]([O:2][CH3:1])[CH2:4][CH2:5]2)[N:15]=1
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).
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