反应详情

温度

80 °C

A mixture of K2CO3 (0.12 g, 0.86 mmol), Pd(PPh3)4 (0.099 g, 0.086 mmol), 3-(7-bromo-4-methyl-3-oxo-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-ylamino)-azetidine-1-carboxylic acid tert-butyl ester ((Example 1, Step B, 0.20 g, 0.43 mmol) and 4,4,6-trimethyl-2-(3,3,3-trifluoroprop-1-en-2-yl)-1,3,2-dioxaborinane (0.38 g, 1.7 mmol) in DME (15 mL) and water (2.5 mL) was stirred at 80° C. overnight. The reaction mixture was cooled to ambient temperature. EtOAc (50 mL) and water (30 mL) were added and the organic portion was separated, dried over anhydrous Na2SO4, filtered and concentrated in vacuo. The residue was purified by preparative TLC (eluting with 50% EtOAc in petroleum ether) to give 3-[4-methyl-3-oxo-7-(1-trifluoromethyl-vinyl)-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-ylamino]-azetidine-1-carboxylic acid tert-butyl ester (0.14 g, 68%). 1H NMR (CDCl3, 400 MHz): δ 8.14 (brs, 1H), 6.83 (s, 1H), 6.28 (s, 1H), 5.92 (s, 1H), 5.73 (s, 1H), 4.66 (q, J=6.8 Hz, 1H), 4.56 (d, J=12.8 Hz, 2H), 4.26 (m, 2H), 4.16 (m, 1H), 4.04 (m, 1H), 3.70 (m, 2H), 1.53 (t, J=6.8 Hz, 3H), 1.48 (s, 9H).

1. temperatureThe reaction mixture was cooled to ambient temperature
2. customthe organic portion was separated
3. dry with materialdried over anhydrous Na2SO4
4. filtrationfiltered
5. concentrationconcentrated in vacuo
6. customThe residue was purified by preparative TLC (eluting with 50% EtOAc in petroleum ether)