62.2% |
With bis-triphenylphosphine-palladium(II) chloride; sodium carbonate; In 1,2-dimethoxyethane; water; for 2.0h;Reflux; |
A solution of 6g (771 mg, 2.012 mmol), (2-fluoro-4-pyridinyl)boronic acid (425 mg, 3.02 mmol),bis(triphenylphosphine)palladium(II) chloride (70.6 mg, 0.101 mmol) and Na2CO3 (1066 mg,10.06 mmol) in DME (20 mL) and water (2 mL) was stirred at reflux for 2 hours. The mixturewas then diluted with EA (50 mL) and water (50 mL). The organic layer was separated and theaqueous layer was extracted with ethyl acetate (50 mL*2). The combined organic layer wasconcentrated and the crude was purified by silica gel eluting with 0-10% MeOH/DCM (1%ammonia) to give the title compound 8i (500 mg, 1.252 mmol, 62.2 % yield) as an off-white solid. |
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With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; water; for 2.0h;Reflux; |
(2-Fluoro-4-pyridinyl)boronic acid (425 mg, 3.02 mmol),bis(triphenylphosphine)palladium(ll) chloride (70.6 mg, 0.10 mmol) and sodium carbonate (1066 mg, 10.06 mmol) as a solution in 2 ml of water was added to a solution of 5-bromo-2-[(phenylmethyl)oxy]-N-3-pyridinylbenzamide (may be prepared as described in example 2; 771 mg, 2.01 mmol) in 1 ,2-dimethoxyethane (20 ml). The mixture was heated to reflux for 2 hours. The mixture was diluted with ethyl acetate (50 ml) and water (50 ml). The organic layer was separated and the aqueous layer was extracted with ethyl acetate (2 x 50 ml). The organics were combined and evaporated. The residue was purified by chromatography on silica eluting with 0- 0% methanol/ dichloromethane 1 % ammonia to yield the title compound as an off-white solid. 500 mg. MS (electrospray): m/z [ +H]+ = 400H NMR (400 MHz, CHLOROFORM-tf) 5.36 (2 H, s), 7.18 - 7.32 (2 H, m), 7.32 - 7.44 (2 H, m), 7.49 - 7.66 (6 H, m) ,7.89 (1 H, dd, J=8.55, 2.19 Hz), 8.01 (1 H, d, J=7.45 Hz), 8.12 (1 H, d, J=1.53 Hz), 8.25 (2 H, t, J=5.04 Hz), 8.60 (1 H, d, J=2.19 Hz). |