反应详情

温度

75 °C

To a solution of 4-[8-(4-iodo-2-methoxy-pyridin-3-yl)-6-methyl-9H-purin-2-yl]-piperazine-1-carboxylic acid tert-butyl ester (1.4 g, 2.54 mmol) in glacial acetic acid (30 mL) was added 11.6 M HCl (30 mL). The reaction mixture was stirred at 75° C. for 6 hours in a sealed tube and concentrated. The residue was dissolved in CH2Cl2 (250 mL) followed by the addition of triethylamine (2.78 mL, 20 mmol). The solution was cooled to 0° C. and di t-butyl dicarbonate (573 mg, 2.63 mmol) was added. The reaction mixture was stirred at 23° C. for 2 hours, poured on saturated NaHCO3 solution and extracted with CH2Cl2 (3×200 mL). The combined organic layers, were dried over MgSO4 and concentrated to give the title compound as a yellow solid. (0.691 g, 62%). HPLC 93%; LCMS (+ESI, M+H+) m/z 446; IR (KBr, cm−1) 3431, 2974, 1700, 1506, 1229; 1H NMR (400 MHz, DMSO+D2O) δ 7.64 (d, J=7.0 Hz, 0.7H), 7.32 (d, J=7.0 Hz, 0.3H), 6.89 (d, J=7.0 Hz, 0.3H), 6.59 (d, J=7.0 Hz, 0.7H), 3.75 (br s, 4H), 3.45 (br s, 4H), 2.60 (s, 3H), 1.45 (s, 9H).

1. concentrationconcentrated
2. dissolutionThe residue was dissolved in CH2Cl2 (250 mL)
3. temperatureThe solution was cooled to 0° C.
4. stirringThe reaction mixture was stirred at 23° C. for 2 hours
5. extractionextracted with CH2Cl2 (3×200 mL)
6. dry with materialThe combined organic layers, were dried over MgSO4
7. concentrationconcentrated