反应详情

温度

90 °C

To a mixture of (2-fluorophenyl)boronic acid (0.051 g, 0.365 mmol), (3R,4R)-4-((R)-7-bromo-4-methyl-3-oxo-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-yl)-3-methyl-piperidine-1-carboxylic acid tert-butyl ester (0.12 g, 0.243 mmol) and K2CO3 (0.067 g, 0.486 mmol) in dioxane (12 mL) and water (2 mL) was added PdCl2(dppf)-CH2Cl2 adduct (0.020 g, 0.024 mmol) and the reaction mixture was stirred at 90° C. overnight. The reaction mixture was cooled to ambient temperature, concentrated in vacuo and the residue was purified by column chromatography on silica gel (eluting with 3-30% EtOAc in petroleum ether) to give (3R,4R)-4-[(R)-7-(2-fluoro-phenyl)-4-methyl-3-oxo-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-yl]-3-methyl-piperidine-1-carboxylic acid tert-butyl ester (0.076 g, 61%) as a colorless solid. 1H NMR (CDCl3, 400 MHz) δ 8.34 (brs, 1H), 7.44-7.32 (m, 1H), 7.24-7.11 (m, 3H), 6.85 (s, 1H), 6.73 (brs, 1H), 4.80 (brs, 1H), 4.70-4.53 (m, 2H), 4.43-4.17 (m, 1H), 3.90-3.60 (m, 1H), 2.89 (brs, 1H), 2.60 (brs, 2H), 1.56 (d, J=6.8 Hz, 3H), 1.46 (m, 10H), 0.72 (m, 3H). LC/MS (Table 1, Method 25), Rt=0.948 min.; MS m/z: 509 [M+H]+& 453 [M+H−56]+. SFC (Table 1, Method 46), Rt=6.21 min.

1. temperatureThe reaction mixture was cooled to ambient temperature
2. concentrationconcentrated in vacuo
3. customthe residue was purified by column chromatography on silica gel (eluting with 3-30% EtOAc in petroleum ether)