反应详情

温度

90 °C

A degassed solution of potassium carbonate (0.432 g, 3.13 mmol), PdCl2(dppf)-CH2Cl2 adduct (0.255 g, 0.313 mmol), 3-[((R)-7-bromo-4-methyl-3-oxo-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-yl)-methyl-amino]-3-methyl-azetidine-1-carboxylic acid tert-butyl ester (prepared from 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 (Example #148, Step G) using the similar procedure detailed in Example #102, Step A), 0.618 g, 1.25 mmol) and (2-fluorophenyl)boronic acid (0.262 g, 1.875 mmol) in 1,4-dioxane (15 mL) and water (3 mL) were heated at 90° C. for 4 h. The reaction mixture was cooled to rt and concentrated in vacuo. The residue was purified by column chromatography on silica gel (eluting with 25% EtOAc in petroleum ether) to afford 3-{[(R)-7-(2-fluoro-phenyl)-4-methyl-3-oxo-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-yl]-methyl-amino}-3-methyl-azetidine-1-carboxylic acid ten-butyl ester (0.540 g, 85%). 1H NMR (CDCl3, 400 MHz): δ 8.14 (s, 1H), 7.35-7.26 (m, 2H), 7.19-7.10 (m, 2H), 6.94 (s, 1H), 6.54 (s, 1H), 4.71-4.56 (m, 3H), 3.86-3.78 (m, 2H), 3.48 (m, 2H), 2.41 (s, 3H). 1.54 (d, J=6.8 Hz, 3H), 1.42 (s, 9H), 1.26 (s, 3H). LC/MS (Table 1, Method 25) Rt=0.913 min., MS m/z: 510 [M+H]+

1. temperatureThe reaction mixture was cooled to rt
2. concentrationconcentrated in vacuo
3. customThe residue was purified by column chromatography on silica gel (eluting with 25% EtOAc in petroleum ether)