反应详情

Add tetrakis(triphenylphosphine)palladium(0) (0.58 g, 0.5 mmol) to a 2 L flask containing a solution of 6-iodo-imidazo[1,2-a]pyridine (6.16 g, 25.2 mmol), 2-(pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole-3-boronic acid (Preparation 5; 6.07 g, 26.5 mmol), and sodium bicarbonate (4.24 g, 50.5 mmol) in 2.5:1 acetonitrile:water (700 mL). Reflux the reaction mixture for 3 h, cool, concentrate to about one half of the volume, extract into dichloromethane (4×250 ml), and concentrate. Flash chromatography using a gradient from 100% hexanes to 100% ethyl acetate (10 min, 45 ml/min), followed by isocratic 100% ethyl acetate (2 L), removes most impurities. Elution with ethyl acetate/methanol mixtures followed by tituration in hot ethyl acetate affords the title compound as a white solid 5.46 g, (72%). MS ES+ m/e 301.9 (M+1). 1H-NMR (400 MHz, DMSO-d6) δ 8.56 (s, 1H), 8.39 (d, J=3.2 Hz, 1H), 7.87 (s, 1H), 7.81-7.76 (m, 2H), 7.51 (d, J=1.2, 1H), 7.42 (d, J=9.2 Hz, 1H), 7.26 (m, 1H), 7.05 (dd, J=9.2, 2 Hz, 1H), 4.2 (t, J=6.6 Hz, 2H, 2.99 (t, J=6.6 Hz, 2H), 2.59 (m, 1H).

1. temperatureReflux the reaction mixture for 3 h
2. temperaturecool
3. concentrationconcentrate to about one half of the volume
4. extractionextract into dichloromethane (4×250 ml)
5. concentrationconcentrate
6. customto 100% ethyl acetate (10 min, 45 ml/min)
7. customremoves most impurities
8. washElution with ethyl acetate/methanol