反应详情

A mixture of 5-cyclopropyl-2-(4-fluorophenyl)-N-methyl-6-(methylsulfonamido)benzofuran-3-carboxamide (1.00 g, 2.49 mmol), (4-(benzyloxy)-3-chlorophenyl)boronic acid (1.31 g, 4.97 mmol), copper(II) acetate (0.903 g, 4.97 mmol), and triethylamine (2.00 mL, 14.4 mmol) in anhydrous DCM (25 mL) was treated with powdered 3 angstrom molecular sieves (2.00 g). The resulting mixture was stirred at RT under air using a drying tube to exclude moisture. After 18 hours the mixture was treated with an additional 1.00 g portion of (4-(benzyloxy)-3-chlorophenyl)boronic acid. After another 18 hours the mixture was diluted with 15 mL of DCM and treated with 1.30 g of (4-(benzyloxy)-3-chlorophenyl)boronic acid, 0.900 g of copper(II) acetate, 2.00 g of 3 angstrom molecular sieves and 2 mL of triethylamine. After 16 more hours the mixture was filtered through Celite to remove solids and the filtrate concentrated to dryness at reduced pressure. The residue was suspended in EtOAc and the undissolved solids removed by filtration through Celite. The filtrate was washed with water (2×), brine (1×), dried over sodium sulfate and concentrated to dryness at reduced pressure. The crude material was purified by flash chromatography (silica gel, gradient from DCM to 7:3 DCM/EtOAc) followed by recrystallization from hexane/EtOAc to afford the title compound (0.83 g, 54%) as an off white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.40-8.47 (m, 1H) 8.20 (s, 1H) 7.93-8.00 (m, 2H) 7.69 (d, J=2.6 Hz, 1H) 7.52 (dd, J=8.9, 2.7 Hz, 1H) 7.30-7.48 (m, 7H) 7.25 (d, J=9.1 Hz, 1H) 7.14 (s, 1H) 5.21 (s, 2H) 3.33 (s, 3H) 2.82 (d, J=4.6 Hz, 3H) 2.17-2.33 (m, 1H) 0.75-1.09 (m, 3H) 0.42 (br. s., 1H). LCMS (m/z, ES+)=619, 621 (M+H+).

1. additionwas treated with powdered 3 angstrom molecular sieves (2.00 g)
2. filtrationAfter 16 more hours the mixture was filtered through Celite
3. customto remove solids
4. concentrationthe filtrate concentrated to dryness at reduced pressure
5. customthe undissolved solids removed by filtration through Celite
6. washThe filtrate was washed with water (2×), brine (1×)
7. dry with materialdried over sodium sulfate
8. concentrationconcentrated to dryness at reduced pressure
9. customThe crude material was purified by flash chromatography (silica gel, gradient from DCM to 7:3 DCM/EtOAc)
10. customfollowed by recrystallization from hexane/EtOAc