反应详情

温度

100 °C

To a mixture of (S)-3-((R)-7-bromo-4-methyl-3-oxo-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-ylamino)-pyrrolidine-1-carboxylic acid tert-butyl ester (0.6 g, 1.249 mmol), PdCl2(dppf)-CH2Cl2 adduct (0.051 g, 0.060 mmol) and K2CO3 (0.259 g, 1.87 mmol) in dioxane (24 mL) and water (4 mL) was added (E)-2-(2-ethoxyvinyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (0.124 g, 0.62 mmol) and the reaction mixture was stirred at 100° C. for 3 h. The reaction mixture was cooled to ambient temperature and concentrated in vacuo to give the crude product, which was purified by column chromatography on silica gel (eluting with 50% EtOAc in petroleum ether) to give (S)-3-[(R)-7-((E)-2-ethoxy-vinyl)-4-methyl-3-oxo-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-ylamino]-pyrrolidine-1-carboxylic acid tert-butyl ester (0.3 g, 50%) as a light yellow solid. 1H NMR (400 MHz, CDCl3): δ 8.16 (s, 1H), 6.73 (s, 1H), 6.61 (d, J=12.4 Hz, 1H), 6.07 (s, 1H), 5.56 (d, J=12.4 Hz, 1H), 5.23 (s, 1H), 4.65 (m, 1H), 4.37-4.52 (m, 2H), 3.77-3.96 (m, 3H), 3.64 (m, 1H), 3.35 (m, 2H), 3.08-3.31 (m, 1H), 2.06-2.22 (m, 1H), 1.82 (m, 1H), 1.42 (m, 12H), 1.28 (t, J=7.2 Hz, 3H). LC/MS (Table 1, Method 2) Rt=1.097 min.; MS m/z: 472 [M+H]+. SFC (Table 1, Method 37) Rt=1.919 min.

1. temperatureThe reaction mixture was cooled to ambient temperature
2. concentrationconcentrated in vacuo
3. customto give the crude product, which
4. customwas purified by column chromatography on silica gel (eluting with 50% EtOAc in petroleum ether)