反应详情

温度

95 °C

To a stirring solution of methyl 1-(4-cyano-3-fluorophenyl)-6-oxo-4-(piperidin-4-yloxy)-1,6-dihydropyridazine-3-carboxylate HCl (37.2 mg, 0.10 mmol) in NMP (3 mL) at room temperature under argon was added DIPEA (38.8 mg, 0.30 mmol) and 2-chloro-5-propylpyrimidine (23.5 mg, 0.15 mmol). The resulting reaction mixture was heated at 95° C. under argon overnight. 15 mL of EtOAc was added to the reaction mixture. The reaction mixture was washed with water (15 mL), and brine (15 mL). Organic phase was dried (MgSO4), filtered and concentrated. The crude product was directly purified by preparative HPLC (C18 column; 10-100% methanol in water without TFA) to give methyl 1-(4-cyano-3-fluorophenyl)-6-oxo-4-(1-(5-propylpyrimidin-2-yl)piperidin-4-yloxy)-1,6-dihydropyridazine-3-carboxylate (16 mg, white solid, 32%). 1H NMR (400 MHz, CDCl3) δ ppm 0.56-1.12 (m, 3H) 1.37-1.67 (m, 2H) 1.70-2.20 (m, 4H) 2.39 (q, J=7.47 Hz, 2H) 3.64-4.09 (m, 7H) 4.02-4.40 (m, 1H) 4.40-4.95 (m, 1H) 6.31 (s, 1H) 7.45-7.91 (m, 3H) 7.91-8.46 (m, 2H). MS (ESI) 493 (M+H).

1. customThe resulting reaction mixture
2. washThe reaction mixture was washed with water (15 mL), and brine (15 mL)
3. dry with materialOrganic phase was dried (MgSO4)
4. filtrationfiltered
5. concentrationconcentrated
6. customThe crude product was directly purified by preparative HPLC (C18 column; 10-100% methanol in water without TFA)