反应详情

A mixture of 5-(4-bromophenyl)-1-methyl-1H-pyrazole (0.50 g, 2.10 mmols,), 4-{3-[(tri-isopropylsilyl)thio]phenyl}tetrahydro-2H-pyran-4-carboxamide (0.83 g, 2.10 mmols), Tetrakis(triphenylphosphine)palladium(0) (243 mg, 0.10 equivalents), bis[(2-diphenyl-phosphino)]phenyl ether (113 mg, 0.10 equivalents), and 1.0 M potassium tert-butoxide in THF (6.3 mmols, 3 equivalents) in iPrOH (15 mL) that contained 5% water was heated for 4 hours at 90 degrees Celcius in an atmosphere of nitrogen. The reaction mixture was cooled to room temperature and 7 mL of 1N HCl was added. The product was precipitated by the addition of water (30 mL). The precipitate was collected by suction filtration and washed with water (2×20 mL) and cold ethyl ether (4×20 mL). The tan brown solid was dissolved in a small volume of methylene chloride containing 1% methanol and applied to a 140 g cartridge of silica gel. The cartridge was eluted with an acetone:hexane gradient. The appropriate fractions were concentrated and triturated with methanol to produce a white solid (710 mg) as product. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.75-1.84 (m, 3H) 2.40 (d, J=13.54 Hz, 3H) 3.43-3.51 (m, 1H) 3.72 (d, J=11.34 Hz, 3H) 3.84 (s, 3H) 6.40 (d, J=1.46 Hz, 1H) 7.02 (s, 1H) 7.22-7.30 (m, 2H) 7.34 (d, J=8.05 Hz, 1H) 7.38-7.43 (m, 2H) 7.45-7.52 (m, 3H). HRMS calc M+H, 394.1589, found 394.1630.

1. temperaturewas heated for 4 hours at 90 degrees Celcius in an atmosphere of nitrogen
2. customThe product was precipitated by the addition of water (30 mL)
3. filtrationThe precipitate was collected by suction filtration
4. washwashed with water (2×20 mL) and cold ethyl ether (4×20 mL)
5. dissolutionThe tan brown solid was dissolved in a small volume of methylene chloride containing 1% methanol
6. washThe cartridge was eluted with an acetone
7. concentrationThe appropriate fractions were concentrated
8. customtriturated with methanol