Cesium carbonate → Methyl 8-fluoro-7-methyl-4-(1-methyl-1H-pyrazol-4-yl)quinoline-2-carboxylate

Participants

Reaction Steps

Cs2CO3 (345 mg, 1.06 mmol) was added to a mixture of methyl 7-(bromomethyl)-8-fluoro-4-(1-methyl-1H-pyrazol-4-yl)quinoline-2-carboxylate (7-18, 160 mg, 0.42 mmol) and 2-(trifluoromethyl)morpholine (79 mg, 0.51 mmol) in DMF (4.2 mL). After stirring at room temperature for 2 h, the mixture was diluted with EtOAc, washed with H2O, then brine. The organic layer was dried over Na2SO4, filtered and concentrated. The residue was purified by column chromatography on silica gel, eluting with EtOAc/Hexane (0-100%) to afford methyl 8-fluoro-7-methyl-4-(1-methyl-1H-pyrazol-4-yl)quinoline-2-carboxylate as racemic mixture (31.4 mg, 16%). LRMS m/z (M+H)+ 453.3 found, 453.1 required. Chiral separation using SFC chromatography provided (R)-methyl 8-fluoro-4-(1-methyl-1H-pyrazol-4-yl)-7-((2-(trifluoromethyl)morpholino)methyl)quinoline-2-carboxylate (7-19a, 15 mg) and (S)-methyl 8-fluoro-4-(1-methyl-1H-pyrazol-4-yl)-7-((2-(trifluoromethyl)morpholino)methyl)quinoline-2-carboxylate (7-19b, 14.3 mg).

Provenance & Evidence