Triphenylphosphine → HCID 69085829, compound

Participants

Reaction Steps

(4R,5R)-4-(5-ethynylpyridin-3-yl)-5-(3-fluorophenyl)oxazolidin-2-one (50 mg, 0.177 mmol; prepared in analogous fashion to the preparation of (4R,5R)-5-(2,5-difluorophenyl)-4-(5-ethynylpyridin-3-yl)oxazolidin-2-one starting from 3-fluorobenzaldehyde in place of 2,5-difluorobenzaldehyde), 2-bromopyrazine (31.0 mg, 0.195 mmol), bis(triphenylphosphine) palladium (II) chloride (6.22 mg, 8.86 mmol), triphenylphosphine (9.29 mg, 0.035 mmol), and copper (I) iodide (1.687 mg, 8.86 mmol) were combined in a microwave vial. Dimethylformamide (0.250 mL) and diisopropylethylamine (0.75 mL) were added resulting in a biphasic mixture. Nitrogen was bubbled through the vessel for 10 min, the vessel was capped and the reaction was run at 120° C. for 25 min on a Biotage microwave reactor. The diisopropylethylamine removed in vacuo, the remaining solution was diluted with methanol and the solution was purified via preparative liquid chromatography (Sunfire C18 19×100 mm 5 nm, A=95% H2O/5% Acetonitrile, B=95% Acetonitrile/5% H2O, Modifier 10 mM Ammonium Acetate, 0.00 min=20% B, 8.0 min=100% B, 13.0 min=100% B, Flow rate=25 mL/min) providing (4R,5R)-5-(3-fluorophenyl)-4-(5-(pyrazin-2-ylethynyl)pyridin-3-yl)oxazolidin-2-one (31 mg; 48%) as an amber foam. 1H NMR (500 MHz, CDCl3) δ ppm 8.89 (1H, br. s.), 8.81 (1H, s), 8.63 (1H, d, J=1.53 Hz), 8.57 (1H, d, J=2.44 Hz), 8.52 (1H, br. s.), 7.97 (1H, s), 7.41 (1H, td, J=7.93, 5.49 Hz), 6.94-7.19 (3H, m), 5.61 (1H, br. s.), 5.30 (1H, d, J=7.32 Hz), 4.81 (1H, d, J=7.32 Hz), Mass Spectral Anal. Calcd. for [M+H]+ C20H13FN4O2: 361.1. found 361.2.

Provenance & Evidence