Cesium carbonate → racemic 3-methyl-5-{[4-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1H-pyrazol-1-yl]methyl}-1,3-oxazolidin-2-one

Participants

Reaction Conditions

Reaction Steps

N-[3-Methyl-5-(1H-pyrazol-4-yl)phenyl]-4-(trifluoromethyl)pyrimidin-2-amine (100 mg, 0.31 mmol), 5-(chloromethyl)-3-methyl-1,3-oxazolidin-2-one (56.2 mg, 0.38 mmol), and cesium carbonate (122 mg, 0.38 mmol) were dissolved in DMA (1 mL). The mixture was then heated by microwave irradiation to 140° C. for 1.5 hours. Additional 5-(chloromethyl)-3-methyl-1,3-oxazolidin-2-one (30 mg, 0.19 mmol) was added and the mixture heated by microwave irradiation to 140° C. for 30 minutes. The reaction was cooled to room temperature, diluted with water (3 mL) and ACN (3 mL) then filtered through a syringe filter and concentrated under reduced pressure. The residue was purified by reverse phase preparative HPLC (45 to 80% ACN/water with 0.1% TFA modifier). The free base was liberated using PL-HCO3 cartridges (Stratospheres™, 0.9 mmol) and lyophilized to afford racemic 3-methyl-5-{[4-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1H-pyrazol-1-yl]methyl}-1,3-oxazolidin-2-one. MS ESI calcd. for C20H20F3N6O2 [M+H]+ 433. found 433. 1H NMR (500 MHz, DMSO-d6) δ 10.12 (s, 1H), 8.80 (d, J=3.9 Hz, 1H), 8.04 (s, 1H), 7.82 (s, 1H), 7.80 (s, 1H), 7.35 (s, 1H), 7.24 (d, J=3.4 Hz, 1H), 7.06 (s, 1H), 4.90-4.79 (m, 1H), 4.45-4.32 (m, 2H), 3.65 (t, J=8.9 Hz, 1H), 3.40 (dd, J=6.2, 9.0, 1H), 2.68 (s, 3H), 2.29 (s, 3H).

Provenance & Evidence