反应详情

In a flask placed under an argon flow, 2 g (3.82 mmol) of methyl 2-((3-iodoimidazo[1,2-a]pyridin-2-yl)methoxy)benzoate were dissolved in 8 ml of dimethylformamide with magnetic stirring. To this solution were added: 0.074 g (0.382 mmol) of copper iodide, 0.551 g (4.59 mmol) of 1-ethynyl-4-fluorobenzene and 8 ml (57.3 mmol) of triethylamine. The reaction medium was degassed with argon for 10 min before adding 0.35 g (0.382 mmol) of Pd2(dba)3. The mixture was stirred at r.t. for 16 h before being treated with 100 ml of a saturated NaCl aqueous solution. The aqueous phase was extracted with 2×100 ml of ethyl acetate. The combined organic phases were washed with 100 ml of a saturated NaCl aqueous solution, dried on Na2SO4 which was then removed by filtration. The obtained filtrate was concentrated in vacuo. The crude residue was purified by flash chromatography on a silica gel cartridge (eluent: heptane/ethyl acetate, 1/1, v/v). 1.36 g (yield=84%) of methyl 2-((3-((4-fluorophenyl)ethynyl) imidazo[1,2-a]pyridin-2-yl)methoxy)benzoate were obtained as a pale brown solid. LC-MS: m/z=401 (MH+); UV purity at 254 nm=98%. 1H NMR (300 MHz, DMSO) δ 8.63 (d, J=6.7 Hz, 1H), 7.75-7.59 (m, 4H), 7.48 (ddd, J=15.9, 11.5, 4.8 Hz, 2H), 7.40-7.26 (m, 3H), 7.13 (t, J=6.8 Hz, 1H), 7.01 (t, J=7.4 Hz, 1H), 5.40 (s, 2H), 3.68 (s, 3H).

1. customIn a flask placed under an argon
2. additionTo this solution were added
3. customThe reaction medium was degassed with argon for 10 min
4. extractionThe aqueous phase was extracted with 2×100 ml of ethyl acetate
5. washThe combined organic phases were washed with 100 ml of a saturated NaCl aqueous solution
6. customdried on Na2SO4 which
7. customwas then removed by filtration
8. concentrationThe obtained filtrate was concentrated in vacuo
9. customThe crude residue was purified by flash chromatography on a silica gel cartridge (eluent