反应详情

A mixture of 3-((R)-7-bromo-4-methyl-3-oxo-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-ylamino)-3-methyl-azetidine-1-carboxylic acid tert-butyl ester (12.7 g, 26.4 mmol), (E)-2-(2-ethoxyvinyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (7.85 g, 39.7 mmol), Pd(dppf)Cl2.CH2Cl2 adduct (4.32 g, 5.29 mmol) and K2CO3 (7.31 g, 52.9 mmol) in dioxane (210 mL) and water (35 mL) was stirred at 80° C. overnight. The reaction mixture was cooled to ambient temperature and concentrated in vacuo. The residue was purified by column chromatography on silica gel (eluting with 20-50% EtOAc in petroleum ether) to give 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]-3-methyl-azetidine-1-carboxylic acid tert-butyl ester (9 g, 72%). 1H NMR (CD3OD, 400 MHz): δ 6.88 (s, 1H), 6.81 (d, J=12.5 Hz, 1H), 5.99 (brs, 1H), 5.85 (d, J=12.5 Hz, 1H), 4.97-4.93 (m, 1H), 4.70 (m, 2H), 4.06 (m, 2H), 3.93 (m, 4H), 1.61 (s, 3H), 1.48-1.44 (m, 12H), 1.33 (s, 3H).

1. concentrationconcentrated in vacuo
2. customThe residue was purified by column chromatography on silica gel (eluting with 20-50% EtOAc in petroleum ether)