反应详情

To a solution of N-(4-fluorobenzyl)-3-hydroxy-4-oxo-10-((oxo(1-piperazinyl)acetyl)amino)-4,6,7,8,9,10-hexahydro-7,10-ethanopyrimido[1,2-a]azepine-2-carboxamide (25 mg, 0.049 mmol) in CH2Cl2 (2 mL) was added triethylamine (0.034 mL, 0.244 mmol), followed by acetyl chloride (0.017 mL, 0.244 mmol) and the resulting mixture stirred at room temperature. After 16 h, the reaction mixture was concentrated to give crude product which was dissolved in methanol (2 mL) and treated with 2M dimethylamine in methanol (0.5 mL). The resulting reaction mixture was stirred at 60° C. for 2 h then cooled and purified by preparative HPLC to afford the title compound as a brown solid (13 mg, 46% yield). 1H NMR (500 MHz, CDCl3) δ: 12.05 (1 H, brs), 8.53 (1 H, brs), 8.48 (1 78, 5.65 Hz), 7.07 (2H, t, J=8.24 Hz), 4.66 (2 H, d, J=5.80 Hz), 4.24 (2 H, d, J=3.05 Hz), 4.18 (1 H, brs), 3.95-4.03 (1 H, m), 3.75 (2 H, brs), 3.46-3.63 (4 H, m), 2.64-2.73 (2 H, m), 2.51-2.58 (1 H, m), 2.11 (3 H, d, J=9.46 Hz), 1.95-2.14 (4 H, m), 1.76-1.82 (2 H, m). LCMS (M+H)=555.56. HPLC purity: >95%.

1. concentrationthe reaction mixture was concentrated
2. customto give crude product which
3. customThe resulting reaction mixture
4. stirringwas stirred at 60° C. for 2 h
5. temperaturethen cooled
6. custompurified by preparative HPLC