反应详情

温度

90 °C

To a mixture of ethyl 10-((((3R)-3-fluoro-1-pyrrolidinyl)(oxo)acetyl)(methyl)amino)-4-oxo-3-((phenylcarbonyl)oxy)-4,6,7,8,9,10-hexahydro-7,10-ethanopyrimido[1,2-a]azepine-2-carboxylat (35 mg, 0.063 mmol) in ethanol (2 mL) was added 2M dimethylamine in methanol (0.063 mL, 0.126 mmol) and the resulting mixture was heated at 50° C. for 1 h. (4-Fluorophenyl)methanamine (0.036 mL, 0.316 mmol) followed by triethylamine (0.044 mL, 0.316 mmol) were added and the mixture heated at 90° C. for 18 h. The reaction mixture was then cooled, concentrated and purified by preparative HPLC to afford the title compound (17 mg, 51% yield) as an off-white solid. 1H NMR (500 MHz, CDCl3) δ: 11.96 (1 H, brs), 9.45 (1 H, brs), 7.34-7.40 (2H, m), 6.97 (2 H, t, J=8.70 Hz), 5.32-5.39 (0.5 H, m), 5.20-5.29 (0.5 H, m), 4.76-4.86 (1 H, m), 4.56-4.67 (1 H, m), 4.40-4.52 (1 H, m), 3.86-3.93 (0.5 H, m), 3.74-3.82 (0.5 H, m), 3.34-3.71 (6 H, m), 3.03 (1.2 H, s), 3.02 (1.8 H, s), 2.49 (1 H, brs), 2.29-2.41 (1 H, m), 1.99-2.09 (4 H, m), 1.76-1.83 (2 H, m), 1.44-1.51 (1 H, m). LCMS (M+H)=530.61. HPLC purity: >95%.

1. additionwere added
2. temperatureThe reaction mixture was then cooled
3. concentrationconcentrated
4. custompurified by preparative HPLC