反应详情

温度

75 °C

485 mg (1.00 mmol) of 3-(2-methoxy-phenyl)-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-b]pyridine, 379 mg (1.20 mmol) of 5-bromo-2-tert-butoxycarbonylamino-benzoic acid and 40 mg (49 μmol) of dichloro[1,1′-bis(diphenylphoshino)ferrocene]palladium(II) dichloromethane adduct were placed in a vial. 8 mL of acetonitrile and 8 mL of a saturated aqueous solution of sodium bicarbonate were added. The vial was closed and the mixture heated to 75° C. for 17 h. The crude mixture was distributed between ethyl acetate and 10% aqueous citric acid. The aqueous layer was extracted twice with ethyl acetate. The combined organic phases were washed with brine, dried over sodium sulfate and evaporated. The crude was purified by flash chromatography on silica gel using a gradient of ethyl acetate in hexanes to afford 204 mg (0.35 mmol, 35%) of 2-tert-butoxycarbonylamino-5-[3-(2-methoxy-phenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-b]pyridin-5-yl]-benzoic acid as a yellow solid. 1H NMR (500 MHz, DMSO-d6) δ 13.80 (s, br. 1H), 10.56 (s, 1H), 8.90 (d, 1H), 8.42 (d, 1H), 8.35 (d, 1H), 8.28 (d, 1H), 8.01 (dd, 1H), 7.65 (dd, 1H), 7.50 (ddd, 1H), 7.26 (ddd, 1H), 7.25 (d(d), 1H), 7.11 (ddd, 1H), 5.86 (s, 2H), 8.87 (s, 3H), 3.70 (t, 2H), 1.50 (s, 9H), 0.87 (t, 2H), −0.09 (s, 9H) MS: m/z 591.2 (M+H+), 613.2 (M+Na+).

1. customThe vial was closed
2. extractionThe aqueous layer was extracted twice with ethyl acetate
3. washThe combined organic phases were washed with brine
4. dry with materialdried over sodium sulfate
5. customevaporated
6. customThe crude was purified by flash chromatography on silica gel using a gradient of ethyl acetate in hexanes