反应详情

温度

90 °C

Morpholine (0.062 mL, 0.711 mmol) was added to a THF (1 mL) solution of (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-{[5-(5-isopropyl-2-methoxypyridin-3-yl)-2-(methylsulfonyl)pyrimidin-4-yl]methyl}-4-methyl-1,3-oxazolidin-2-one (INTERMEDIATE 17, 90 mg, 0.142 mmol) in a microwave vial. The vial was capped, then heated for 15 minutes at 90° C. in a BIOTAGE microwave reactor. LCMS showed complete conversion to product. The reaction was diluted with 2 mL CH3CN and loaded directly onto an X-Bridge 21.2×150 mm RP column. Using a 10-100% acetonitrile/water (0.1% NH4OH) linear gradient at 15 mL/minutes over 20 minutes, the product of interest was recovered and lyophilized to give the titled compound as a white solid. LCMS (M+H)+: 640.5. 1H NMR (CDCl3, 500 MHz): δ 8.17 (s, 1H), 8.10 (d, J=2.2 Hz, 1H), 7.91 (s, 1H), 7.75 (s, 2H), 7.35 (d, J=2.2 Hz, 1H), 5.64 (d, J=8.5 Hz, 1H), 4.72 (d, J=17.1 Hz, 1H), 4.32 (m, 1H), 4.00 (d, J=17.2 Hz, 1H), 3.94 (s, 3H), 3.88 (m, 4H), 3.83 (m, 4H), 2.96 (m, 1H), 1.29 (d, J=7.0 Hz, 6H), 0.71 (d, J=6.5 Hz, 3H). SPA IC50: 229 nM.

1. customThe vial was capped
2. customover 20 minutes
3. customthe product of interest was recovered