反应详情

温度

130 °C

A sealable tube was charged with 2-chloro-4-morpholin-4-yl-6-(4-morpholin-4-yl-piperidin-1-ylmethyl)-thieno[3,2-d]pyrimidine (0.100 g, 0.229 mmol), isoquinoline-5-boronic acid (0.048 g, 0.275 mmol), dichlorobis(triphenylphosphine)palladium(II) (0.008 g, 0.012 mmol), 1 N aqueous sodium carbonate solution (1 mL) and acetonitrile (3 mL). The vessel was evacuated and back-filled with argon three times then sealed and heated at 130° C. for 90 min. The reaction mixture was cooled, concentrated, redissolved in ethyl acetate and filtered through celite. The filtrates were concentrated then purified by chromatography (silica, 10 to 20% methanol in dichloromethane) to give 101 (0.033 g, 27%) as a yellow solid. MS m/e 531 [M+H]+; 1H NMR (300 MHz, CDCl3) δ ppm 1.54-1.71 (m, 2 H) 1.87 (d, J=11.3 Hz, 2 H) 2.09-2.30 (m, 3 H) 2.52-2.63 (m, 4 H) 3.01-3.11 (m, 2 H) 3.70-3.78 (m, 4 H) 3.85 (s, 2 H) 3.87-3.94 (m, 4 H) 4.03-4.12 (m, 4 H) 7.35 (s, 1 H) 7.67-7.75 (m, 1 H) 8.06 (d, J=8.3 Hz, 1 H) 8.31-8.37 (m, 1 H) 8.52-8.58 (m, 1 H) 8.61-8.67 (m, 1 H) 9.30 (s, 1 H)

1. customThe vessel was evacuated
2. additionback-filled with argon three times
3. customthen sealed
4. temperatureThe reaction mixture was cooled
5. concentrationconcentrated
6. dissolutionredissolved in ethyl acetate
7. filtrationfiltered through celite
8. concentrationThe filtrates were concentrated
9. customthen purified by chromatography (silica, 10 to 20% methanol in dichloromethane)