2-Bromo-6-methylpyridine → Pyrazine-2-carboxylic acid [5-(6-methyl-pyridin-2-ylethynyl)-bicyclo[3.2.1]oct-1-yl]-amide

Participants

Reaction Conditions

Reaction Steps

To a stirred mixture of intermediate 1, N-(5-ethynylbicyclo[3.2.1]octan-1-yl)pyrazine-2-carboxamide (40 mg, 0.16 mmol) and 2-bromo-6-methylpyridine (30 mg, 0.18 mmol) in TEA (0.5 mL) and acetonitrile (2 mL) was added Pd(PPh3)4 (2 mg, 0.02 mmol), followed by an addition of CuI (4 mg, 0.02 mmol). After heated at 70° C. for three hours, the reaction was cooled to room temperature, diluted with ethyl acetate (30 mL), washed with water and brine, dried over Na2SO4 and concentrated under reduced pressure. The resulting residue was purified by Prep HPLC to afford 20 mg (36%) of the title compound, pyrazine-2-carboxylic acid [5-(6-methyl-pyridin-2-ylethynyl)-bicyclo[3.2.1]oct-1-yl]-amide, as a white solid. 1HNMR (500 MHz, CDCl3): δ 9.40 (s, 1H), 8.75 (s, 1H), 8.51 (s, 1H), 7.91 (s, 1H), 7.51 (t, J=7.5 Hz, 1H), 7.21 (d, J=8.0 Hz, 1H), 7.06 (d, J=7.5 Hz, 1H), 2.55-2.52 (m, 4H), 2.29-1.76 (m, 11H); ESI-MS m/z: 347 (M+H)+.

Provenance & Evidence