反应详情

6-Chloro-N-cyclopropylmethylnicotinamide (Intermediate 1) (18.5 mg, 0.073 mmol) and 4-methyl-N-(3-pyridin-2-yl-phenyl)-3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzamide (Intermediate 6) (30 mg, 0.072 mmol), aqueous sodium carbonate (2N, 0.5 ml) and tetrakis(triphenylphosphine)palladium (4 mg) were heated at 90° C. in DMF (1 ml) for 4 hours. The reaction was absorbed onto silica, applied to a bond-elut (5 g, silica) and eluted with an ethylacetate/cyclohexane (0 to 100%) and then acetone. The solvent was evaporated from the product fractions under vacuum and the residue triturated with ether to give N-cyclopropylmethyl-6-[2-methyl-5-(3-pyridin-2-yl-phenylcarbamoyl)-phenyl]-nicotinamide as a white solid (20 mg). LCMS: retention time 3.18 min, MH− 463. NMR: δH [2H6]-DMSO 10.43, (1H, s), 9.14, (1H, s), 8.86, (1H, t), 8.69, (1H, s), 8.53, (1H, s), 8.34, (1H, d), 8.11, (1H, s), 8.01, (1H, d), 7.95-7.89, (3H, m), 7.81-7.78, (2H, m), 7.53-7.46, (2H, m), 7.38, (1H, t), 3.21, (2H, t), 2.44, (3H, s), 1.07, (1H, m), 0.47, (2H, m), 0.27, (2H, m).

1. customThe reaction was absorbed onto silica
2. washeluted with an ethylacetate/cyclohexane (0 to 100%)
3. customThe solvent was evaporated from the product fractions under vacuum
4. customthe residue triturated with ether