21.07% |
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium carbonate; In tetrahydrofuran; water; at 80℃; for 2h;Inert atmosphere; |
Embodiment 259 4-(4-cyclobutyl-3-(6-((2S,6R)-2,6-dimethylmorpholino)pyridin-3-yl)quinolin-8-yl) benzonitrile Pd(dppf)Cl2 (36.59 mg, 50 mumol) and Na2CO3 (105.99 mg, 1 mmol) were added into a solution of 259-1 (227.48 mg, 500 mumol), <strong>[849052-26-2]cyclobutyl boric acid</strong> (99.92 mg, 1 mmol) in THF / H2O (2 mL). Under nitrogen gas atmosphere, the mixture was heated to 80C and reacted for 2h, then poured into H2O (10 mL). The reaction mixture was extracted with EtOAc (10 mL*3). The organic phase was washed with brines (30 mL), dried over anhydrous MgSO4, concentrated under vacuum. The residue was purified by prep-HPLC to deliver the target product (50 mg, yield 21.07%). MS ESI calcd for C31H30N4O [M+H]+ 475, found 475. 1HNMR (400 MHz, CHLOROFORM-d) delta ppm 8.70 (s, 1 H), 8.09 - 8.23 (m, 2 H), 7.79 (d, J= 3.01 Hz, 4 H), 7.58 - 7.71 (m, 2 H), 7.46 - 7.57 (m, 1 H), 6.63 - 6.84 (m, 1 H), 4.26 - 4.50 (m, 1 H), 4.12 (d, J= 12.55 Hz, 2 H), 3.76 (d, J= 6.53 Hz, 2 H), 2.54 - 2.69 (m, 2 H), 2.37 (d, J= 8.53 Hz, 2 H), 1.84 - 2.15 (m, 4 H), 1.65 - 1.78 (m, 1 H), 1.17 - 1.38 (m, 8 H). |