Triphenylphosphine → 3-Methyl-6-(4-(methylsulfonyl)phenyl)-N-phenylpyrazine-2-carboxamide

Participants

Reaction Steps

A solution of 3-bromo-6-(4-methylsulfonylphenyl)-N-phenyl-pyrazine-2-carboxamide (89.4 mg, 0.1634 mmol) and palladium; triphenylphosphane (9.441 mg, 0.008170 mmol) in THF (1 mL) was treated with chloro(methyl)zinc (490.2 μL of 2 M, 0.9804 mmol) and left to stir for 16 hours at ambient temperature. The reaction was treated with further chloro(methyl)zinc (490.2 μL of 2 M, 0.9804 mmol) and allowed to heat at 60° C. for 7 hours. The mixture was allowed to cool to ambient temperature and concentrated in vacuo. The resultant residue was dissolved in DMSO and purified by reverse phase preparative HPLC [Waters Sunfire C18, 10 mM, 100 Å column, gradient 10%-95% B (solvent A: 0.05% TFA in water; solvent B: CH3CN) over 16 minutes at 25 mL/min]. The fractions were collected, passed through a sodium bicarbonate cartridge and freeze-dried to give the title compound as a white solid (24.6 mg, 41% Yield). 1H NMR (400.0 MHz, DMSO) δ 2.81 (s, 3H), 3.31 (s, 3H), 7.15-7.19 (m, 1H), 7.39-7.43 (m, 2H), 7.82 (d, J=7.6 Hz, 2H), 8.11 (d, J=8.5 Hz, 2H), 8.56 (d, J=8.5 Hz, 2H), 9.44 (s, 1H) and 10.71 (s, 1H) ppm; MS (ES+) 367.98. LCMS retention time, 3.37 min.

Provenance & Evidence