反应详情

温度

90 °C

To a mixture of (2-fluorophenyl)boronic acid (0.019 g, 0.137 mmol), (3S,4S)-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 (0.045 g, 0.091 mmol) and K2CO3 (0.025 g, 0.182 mmol) in dioxane (12 mL) and water (2 mL) was added PdCl2(dppf)-CH2Cl2 adduct (7.45 mg, 9.12 μmol) and the reaction mixture was heated at 90° C. overnight. The reaction mixture was cooled to ambient temperature and concentrated in vacuo. The residue was purified by prep-TLC (eluting with 55% EtOAc in petroleum ether) to give (3S,4S)-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 (0.036 g, 78%) as a white solid. 1H NMR (400 MHz, MeOD) δ 7.48-7.37 (m, 1H), 7.29-7.14 (m, 3H), 6.91 (s, 1H), 6.81 (s, 1H), 4.93 (m, 1H), 4.63-4.58 (m, 2H), 4.23 (m, 1H), 3.81 (m, 1H), 3.03-2.86 (m, 1H), 2.79-2.42 (m, 3H), 2.34-2.11 (m, 2H), 1.50-1.41 (m, 14H), 0.75 (m, 3H). LC/MS (Table 1, Method 4) Rt=2.830 min.; MS m/z: 531 [M+Na]+& 453 [M+H−56]+. SFC (Table 1, Method 46), Rt=6.84 min.

1. temperatureThe reaction mixture was cooled to ambient temperature
2. concentrationconcentrated in vacuo
3. customThe residue was purified by prep-TLC (eluting with 55% EtOAc in petroleum ether)