Sodium hydride → (4S,5S)-4-methyl-5-((4-(3-methyl-5-((4-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)-1H-pyrazol-1-yl)methyl)oxazolidin-2-one

Participants

Reaction Conditions

Reaction Steps

Sodium hydride (60% dispersion in mineral oil, 28 mg, 0.71 mmol) was added to a mixture of N-(3-methyl-5-(1H-pyrazol-4-yl)phenyl)-4-(trifluoromethyl)pyrimidin-2-amine (150 mg, 0.47 mmol) in DMF (3 mL), and the mixture was stirred for 5 minutes. A mixture of tert-butyl ((2S)-4-chloro-3-hydroxybutan-2-yl)carbamate (110 mg, 0.49 mmol) in DMF (2 mL) was added and the mixture was heated to 40° C. for 4 hours. The mixture was then allowed to cool to room temperature and diluted with ethyl acetate and water. The organic layer was separated, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The crude residue was then purified by column chromatography on silica gel. The purified diasteromeric mixture was separated by chiral SFC (Chiralpak ID, 21×250 (mm), 25% CO2 with methanol as the diluent) to afford (4S,5S)-4-methyl-5-((4-(3-methyl-5-((4-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)-1H-pyrazol-1-yl)methyl)oxazolidin-2-one (Isomer 1, early eluting): MS ESI calc'd. for C20H20F3N6O2 [M+H]+ 433. found 433. 1H NMR (500 MHz, DMSO-d6) δ 10.12 (s, 1H), 8.80 (d, J=4.3 Hz, 1H), 8.06 (s, 1H), 7.85-7.76 (m, 2H), 7.73 (s, 1H), 7.35 (s, 1H), 7.24 (d, J=4.6 Hz, 1H), 7.06 (s, 1H), 4.47-4.35 (m, 3H), 3.75-3.59 (m, 1H), 2.29 (s, 3H), 1.10 (d, J=5.8 Hz, 3H).

Provenance & Evidence